unique_id Regulation drug2ferroptosis drug2regulator drug2target regulator to target gene regulator2ferroptosis target_role4ferroptosis Vivo model ReferenceID disease_detail_icd disease_detail in_vitro Cell Line pathway_id Cell_progress
unique00516 Sepsis-associated acute kidney injury induced ferroptosis by increasing iron and lipid peroxidation. Irisin effectively suppressed ferroptosis and alleviated SA-AKI and improved the mitochondria functionviainduction of the SIRT1/Nrf2 signal axis. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor All animals were purchased from the Animal Experimental Center of Wuhan University (ABLS-III Laboratory). C57BL/6 male mice weighing 20-25 g were used for this study. HK-2 cells were seeded into 96-well plates (5 x 105 cells/well) and cultured for 24 h until 80% confluence. Subsequently, we have added LPS (10 ug/ml) into the cultured cells for 22 h to establish the cell model of LPS-induced AKI. REF000705 ICD-11: 1G40 Sepsis-associated acute kidney injury CELL00093 HK-2 Ferroptosis (hsa04216) Cell ferroptosis
unique00516 Sepsis-associated acute kidney injury induced ferroptosis by increasing iron and lipid peroxidation. Irisin effectively suppressed ferroptosis and alleviated SA-AKI and improved the mitochondria functionviainduction of the SIRT1/Nrf2 signal axis. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor All animals were purchased from the Animal Experimental Center of Wuhan University (ABLS-III Laboratory). C57BL/6 male mice weighing 20-25 g were used for this study. HK-2 cells were seeded into 96-well plates (5 x 105 cells/well) and cultured for 24 h until 80% confluence. Subsequently, we have added LPS (10 ug/ml) into the cultured cells for 22 h to establish the cell model of LPS-induced AKI. REF000705 ICD-11: 1G40 Sepsis-associated acute kidney injury CELL00093 HK-2 Ferroptosis (hsa04216) Cell ferroptosis
unique00080 Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor 1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively. REF000134 ICD-11: 2A00 Glioma CELL00043; CELL00243 U251; U373 mTOR signaling pathway (hsa04150); Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00078 Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor 1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively. REF000134 ICD-11: 2A00 Glioma CELL00043; CELL00243 U251; U373 mTOR signaling pathway (hsa04150); Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00079 Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor 1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively. REF000134 ICD-11: 2A00 Glioma CELL00043; CELL00243 U251; U373 mTOR signaling pathway (hsa04150); Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique01630 Dihydroartemisinin (DHA) could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma. Inducer Up regulation Up regulation Up regulation Driver Marker All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days. REF000843 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique01629 Dihydroartemisinin (DHA) could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma. Inducer Down regulation Up regulation Down regulation Suppressor Marker All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days. REF000843 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique00079 Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor 1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively. REF000134 ICD-11: 2A00 Glioma CELL00043; CELL00243 U251; U373 mTOR signaling pathway (hsa04150); Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00078 Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor 1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively. REF000134 ICD-11: 2A00 Glioma CELL00043; CELL00243 U251; U373 mTOR signaling pathway (hsa04150); Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00080 Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor 1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively. REF000134 ICD-11: 2A00 Glioma CELL00043; CELL00243 U251; U373 mTOR signaling pathway (hsa04150); Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique01630 Dihydroartemisinin (DHA) could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma. Inducer Up regulation Up regulation Up regulation Driver Marker All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days. REF000843 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique01629 Dihydroartemisinin (DHA) could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma. Inducer Down regulation Up regulation Down regulation Suppressor Marker All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days. REF000843 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique00923 HSPA5 upregulation increased the expression and activity of glutathione peroxidase 4 (GPX4), which neutralized Dihydroartemisinin-induced lipid peroxidation and thus protected glioma cells from ferroptosis. Ferroptosis might be a novel anticancer mechanism of DHA in glioma and HSPA5 may serve as a negative regulator of DHA-induced ferroptosis. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Specific pathogen-free athymic nude BALB/c mice (4-6 weeks old) were obtained from Guangdong Experimental Animal Centre (Guangzhou, China). To generate murine subcutaneous tumors, cells (for U251: 2 x 106 cells; for U373: 2 x 106 cells) were suspended in 0.2 ml PBS and injected into the flanks of mice (n = 6/group). Tumor volume was measured once every 3 days using calipers. REF000091 ICD-11: 2A00 Glioma CELL00043; CELL00243; CELL00549 U251; U373; HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00070 ALZ003 targeting AR for degradation strongly exhibits the therapeutic effect on glioblastoma, including TMZ-resistant tumor,in vitroandin vivo. Particularly, GPX4 was positively regulated by AR, and overexpression of AR also prevented lipid peroxidation. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor NOD-SCID male mice (8-week-old) were purchased from BioLASCO Taiwan Co., Ltd. (Taipei, Taiwan). For glioblastoma and TMZ-resistant glioblastoma transplantation, luciferase-expressed U87MG cells (2 x 105) and U87MG-R cells (2 x 105) were injected into the cortex, respectively, at the depth of 3 mm using stereotactic guidance and microprocessor single syringe (Harvard Apparatus, Holliston, MA, USA). After 10 days of transplantation, TMZ (15 mg/kg) and ALZ003 were orally and intravenously administrated three times per week, respectively. REF000120 ICD-11: 2A00 Glioblastoma CELL00323; CELL00068 U87MG; A172 Fatty acid metabolism (hsa01212); Apoptosis (hsa04210); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01418 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 ( MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Down regulation Down regulation Driver Suppressor The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01764 Fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor After anesthetizing the nude mice with isoflurane inhalation, we injected 1 x 106 U87 cells that were engineered for the expression of luciferase into the right striatum (3.5 mm from the midline of the brain and 2 mm in front of the coronal suture, injection depth of 3 mm from the brain surface) of the nude mice to establish an intracranial xenograft model. For the detection of pharmacokinetics in mice, RhoB-loaded p28-PLGA NPs were injected into the mice (n = 3) through the tail vein. We collected blood samples at predetermined time points, quantified the RhoB concentrations, and plotted them with time. To characterize NPs for GBM treatment, we randomly divided the tumor-bearing mice into four groups (n = 8) treated with PBS, free fatostatin (25 mg/kg), NPs-FAT (fatostatin equivalent dose at 25 mg/kg), and p28-NPs-FAT (fatostatin equivalent dose at 25 mg/kg). After 7 days of tumor inoculation, the treatment was conducted 3 days per week for 4 weeks. In addition, we performed IVIS imaging of intracranial tumors at 1, 3, and 5 weeks after tumor inoculation to observe tumor progression. IVIS was also used to carry out imaging of IR780-loaded NPs. The mice were monitored regularly and euthanized when they exhibited severe neurological symptoms and/or obvious weight loss (>20% of their body weight). We sacrificed a separate cohort of mice five weeks after tumor inoculation for pathological staining (n = 3). REF000993 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01763 Fatostatin induces ferroptosis by inhibiting the AKT/ mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor After anesthetizing the nude mice with isoflurane inhalation, we injected 1 x 106 U87 cells that were engineered for the expression of luciferase into the right striatum (3.5 mm from the midline of the brain and 2 mm in front of the coronal suture, injection depth of 3 mm from the brain surface) of the nude mice to establish an intracranial xenograft model. For the detection of pharmacokinetics in mice, RhoB-loaded p28-PLGA NPs were injected into the mice (n = 3) through the tail vein. We collected blood samples at predetermined time points, quantified the RhoB concentrations, and plotted them with time. To characterize NPs for GBM treatment, we randomly divided the tumor-bearing mice into four groups (n = 8) treated with PBS, free fatostatin (25 mg/kg), NPs-FAT (fatostatin equivalent dose at 25 mg/kg), and p28-NPs-FAT (fatostatin equivalent dose at 25 mg/kg). After 7 days of tumor inoculation, the treatment was conducted 3 days per week for 4 weeks. In addition, we performed IVIS imaging of intracranial tumors at 1, 3, and 5 weeks after tumor inoculation to observe tumor progression. IVIS was also used to carry out imaging of IR780-loaded NPs. The mice were monitored regularly and euthanized when they exhibited severe neurological symptoms and/or obvious weight loss (>20% of their body weight). We sacrificed a separate cohort of mice five weeks after tumor inoculation for pathological staining (n = 3). REF000993 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00720 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00722 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00070 ALZ003 targeting AR for degradation strongly exhibits the therapeutic effect on glioblastoma, including TMZ-resistant tumor,in vitroandin vivo. Particularly, GPX4 was positively regulated by AR, and overexpression of AR also prevented lipid peroxidation. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor NOD-SCID male mice (8-week-old) were purchased from BioLASCO Taiwan Co., Ltd. (Taipei, Taiwan). For glioblastoma and TMZ-resistant glioblastoma transplantation, luciferase-expressed U87MG cells (2 x 105) and U87MG-R cells (2 x 105) were injected into the cortex, respectively, at the depth of 3 mm using stereotactic guidance and microprocessor single syringe (Harvard Apparatus, Holliston, MA, USA). After 10 days of transplantation, TMZ (15 mg/kg) and ALZ003 were orally and intravenously administrated three times per week, respectively. REF000120 ICD-11: 2A00 Glioblastoma CELL00323; CELL00068 U87MG; A172 Fatty acid metabolism (hsa01212); Apoptosis (hsa04210); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00923 HSPA5 upregulation increased the expression and activity of glutathione peroxidase 4 (GPX4), which neutralized Dihydroartemisinin-induced lipid peroxidation and thus protected glioma cells from ferroptosis. Ferroptosis might be a novel anticancer mechanism of DHA in glioma and HSPA5 may serve as a negative regulator of DHA-induced ferroptosis. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Specific pathogen-free athymic nude BALB/c mice (4-6 weeks old) were obtained from Guangdong Experimental Animal Centre (Guangzhou, China). To generate murine subcutaneous tumors, cells (for U251: 2 x 106 cells; for U373: 2 x 106 cells) were suspended in 0.2 ml PBS and injected into the flanks of mice (n = 6/group). Tumor volume was measured once every 3 days using calipers. REF000091 ICD-11: 2A00 Glioma CELL00043; CELL00243; CELL00549 U251; U373; HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00722 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01763 Fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor After anesthetizing the nude mice with isoflurane inhalation, we injected 1 x 106 U87 cells that were engineered for the expression of luciferase into the right striatum (3.5 mm from the midline of the brain and 2 mm in front of the coronal suture, injection depth of 3 mm from the brain surface) of the nude mice to establish an intracranial xenograft model. For the detection of pharmacokinetics in mice, RhoB-loaded p28-PLGA NPs were injected into the mice (n = 3) through the tail vein. We collected blood samples at predetermined time points, quantified the RhoB concentrations, and plotted them with time. To characterize NPs for GBM treatment, we randomly divided the tumor-bearing mice into four groups (n = 8) treated with PBS, free fatostatin (25 mg/kg), NPs-FAT (fatostatin equivalent dose at 25 mg/kg), and p28-NPs-FAT (fatostatin equivalent dose at 25 mg/kg). After 7 days of tumor inoculation, the treatment was conducted 3 days per week for 4 weeks. In addition, we performed IVIS imaging of intracranial tumors at 1, 3, and 5 weeks after tumor inoculation to observe tumor progression. IVIS was also used to carry out imaging of IR780-loaded NPs. The mice were monitored regularly and euthanized when they exhibited severe neurological symptoms and/or obvious weight loss (>20% of their body weight). We sacrificed a separate cohort of mice five weeks after tumor inoculation for pathological staining (n = 3). REF000993 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01418 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 (MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Down regulation Down regulation Driver Suppressor The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00720 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01764 Fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor After anesthetizing the nude mice with isoflurane inhalation, we injected 1 x 106 U87 cells that were engineered for the expression of luciferase into the right striatum (3.5 mm from the midline of the brain and 2 mm in front of the coronal suture, injection depth of 3 mm from the brain surface) of the nude mice to establish an intracranial xenograft model. For the detection of pharmacokinetics in mice, RhoB-loaded p28-PLGA NPs were injected into the mice (n = 3) through the tail vein. We collected blood samples at predetermined time points, quantified the RhoB concentrations, and plotted them with time. To characterize NPs for GBM treatment, we randomly divided the tumor-bearing mice into four groups (n = 8) treated with PBS, free fatostatin (25 mg/kg), NPs-FAT (fatostatin equivalent dose at 25 mg/kg), and p28-NPs-FAT (fatostatin equivalent dose at 25 mg/kg). After 7 days of tumor inoculation, the treatment was conducted 3 days per week for 4 weeks. In addition, we performed IVIS imaging of intracranial tumors at 1, 3, and 5 weeks after tumor inoculation to observe tumor progression. IVIS was also used to carry out imaging of IR780-loaded NPs. The mice were monitored regularly and euthanized when they exhibited severe neurological symptoms and/or obvious weight loss (>20% of their body weight). We sacrificed a separate cohort of mice five weeks after tumor inoculation for pathological staining (n = 3). REF000993 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01421 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 ( MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Up regulation Up regulation Driver Driver The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01421 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 (MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Up regulation Up regulation Driver Driver The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00303 Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. Inducer Up regulation Up regulation Up regulation Driver Driver The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 106) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm3 after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times. REF000428 ICD-11: 2A00 Glioma CELL00351; CELL00295; CELL00043; CELL00068 U118; U87; U251; A172 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00303 Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. Inducer Up regulation Up regulation Up regulation Driver Driver The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 106) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm3 after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times. REF000428 ICD-11: 2A00 Glioma CELL00351; CELL00295; CELL00043; CELL00068 U118; U87; U251; A172 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01525 Apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor Female BALB/c nude mice (age, 4 weeks old) were purchased from Changzhou Cavens Experimental Animal Co., Ltd. (Changzhou, China).The gliomas from the nude mice were fixed in 10% paraformaldehyde at 4 for 12 h and then dehydrated in different concentrations of ethanol. The tumor tissues were permeabilized using xylene and embedded in paraffin. They were then sliced (0.5 um), rehydrated, and stained with HE at 4 for 10 min and sealed. For IHC assessment of Ki-67 in gliomas, the DAKO Envision system (Dako; Agilent Technologies, Inc.) was used. REF000745 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01526 Apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/ Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor Female BALB/c nude mice (age, 4 weeks old) were purchased from Changzhou Cavens Experimental Animal Co., Ltd. (Changzhou, China).The gliomas from the nude mice were fixed in 10% paraformaldehyde at 4 for 12 h and then dehydrated in different concentrations of ethanol. The tumor tissues were permeabilized using xylene and embedded in paraffin. They were then sliced (0.5 um), rehydrated, and stained with HE at 4 for 10 min and sealed. For IHC assessment of Ki-67 in gliomas, the DAKO Envision system (Dako; Agilent Technologies, Inc.) was used. REF000745 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00719 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00721 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00721 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01526 Apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor Female BALB/c nude mice (age, 4 weeks old) were purchased from Changzhou Cavens Experimental Animal Co., Ltd. (Changzhou, China).The gliomas from the nude mice were fixed in 10% paraformaldehyde at 4 for 12 h and then dehydrated in different concentrations of ethanol. The tumor tissues were permeabilized using xylene and embedded in paraffin. They were then sliced (0.5 um), rehydrated, and stained with HE at 4 for 10 min and sealed. For IHC assessment of Ki-67 in gliomas, the DAKO Envision system (Dako; Agilent Technologies, Inc.) was used. REF000745 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00719 Paeoniflorin (PF) can function as an antitumor agent for glioma treatment by targeting NEDD4L-dependent STAT3 ubiquitination as well as by regulating the Nrf2/GPX4 signaling axis, which might trigger ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor U251 cells (6 x 106) were inoculated into the flanks of 4-to 5-week-old athymic nude mice (Shanghai Laboratory Animal Company, Shanghai, China) subcutaneously to generate a subcutaneous xenograft tumor model. After 2 weeks, the tumor model was successfully constructed, the mice were treated single and combined with 100 mg/kg RSL3 (2 times/week) and 1.0 g/kg/days PF. Tumor volumes were measured every 4 days to draw the growth curve. Mice were sacrificed 4 weeks after cell injection. Tumor xenografts were collected, photographed, and weighed and the tumor apoptosis was analyzed by Tunel staining. REF000938 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01525 Apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor Female BALB/c nude mice (age, 4 weeks old) were purchased from Changzhou Cavens Experimental Animal Co., Ltd. (Changzhou, China).The gliomas from the nude mice were fixed in 10% paraformaldehyde at 4 for 12 h and then dehydrated in different concentrations of ethanol. The tumor tissues were permeabilized using xylene and embedded in paraffin. They were then sliced (0.5 um), rehydrated, and stained with HE at 4 for 10 min and sealed. For IHC assessment of Ki-67 in gliomas, the DAKO Envision system (Dako; Agilent Technologies, Inc.) was used. REF000745 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01420 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 ( MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Up regulation Up regulation Driver Driver The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01420 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 (MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Up regulation Up regulation Driver Driver The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01419 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 ( MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01419 Artesunate triggers ferroptosis in glioblastoma in vitro and in vivo through regulation of iron metabolism and p38 (MAPK14) and ERK signaling pathways. Meanwhile, ART reduced the protein level of GPX4 and FPN1, increased the protein level of DMT1, TfR, ferritin and NCOA4. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor The xenografts were established via the subcutaneous inoculation of U251 cells (1 x 107 cells/per mouse) into the armpit of one mouse. After two weeks of growth, the cancer tissues were cut into pieces with the dimensions of 1.5 x 1.5 x 1.5 mm3 and inoculated subcutaneously into the right armpit of the mice with a puncture needle. When tumor volume reached approximately 80 mm3, mice were randomly divided into four groups (n = 5): Vehicle control, ART (20 mg/kg), ART (40 mg/kg), and TMZ (40 mg/kg). TMZ was used as the positive control. Drugs and vehicle were given by intraperitoneal injection daily for 21 days. Tumor volume and body weight were measured every three days. REF000665 ICD-11: 2A00 Glioblastoma CELL00043 U251 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00475 NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11. Inducer Up regulation Down regulation Down regulation Driver Suppressor Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 106 U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm3, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks. REF000635 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 NF-kappa B signaling pathway (hsa04064); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00304 Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT (SLC7A11) to prevent H2O2 degradation on the other hand. Inducer Up regulation Down regulation Down regulation Driver Suppressor The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 106) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm3 after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times. REF000428 ICD-11: 2A00 Glioma CELL00351; CELL00295; CELL00043; CELL00068 U118; U87; U251; A172 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00304 Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT (SLC7A11) to prevent H2O2 degradation on the other hand. Inducer Up regulation Down regulation Down regulation Driver Suppressor The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 106) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm3 after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times. REF000428 ICD-11: 2A00 Glioma CELL00351; CELL00295; CELL00043; CELL00068 U118; U87; U251; A172 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00475 NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11. Inducer Up regulation Down regulation Down regulation Driver Suppressor Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 106 U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm3, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks. REF000635 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 NF-kappa B signaling pathway (hsa04064); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00016 Pseudolaric acid B (PAB) improved intracellular iron by upregulation of transferrin receptor. The increased iron activated Nox4, which resulted in overproduction of H2O2and lipid peroxides. Moreover, PAB depleted intracellular GSH via p53-mediated xCT (SLC7A11) pathway, which further exacerbated accumulation of H2O2and lipid peroxides. Thus, PAB triggers ferroptosis in glioma cells and is a potential medicine for glioma treatment. Inducer Up regulation Down regulation Down regulation Driver Suppressor Twenty athymic BALB/c nude mice (aged 4 weeks, weight 20-22 g, from Shanghai laboratory animal Center, Shanghai, China) were housed in a specific pathogen-free environment. A total of 1 x 106 logarithmically growing C6 cells in 100 uL of PBS were subcutaneously injected into the right flank of each mouse. Therapeutic experiments were started when the tumor reached about 150 mm3 after about 7 days. The mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 5/group), PAB at the dosage of 10 mg/kg body weight (n = 10/group) and 20 mg/kg body weight (n = 10/group) in the same volume 50 uL once a days for 8 times. REF000040 ICD-11: 2A00 Glioma CELL00044; CELL00043; CELL00610 SHG-44;U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00802 Both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of Acute myeloid leukemia (AML) cells following GSK3368715 treatment. Overall, PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. Inducer Down regulation Up regulation Down regulation Suppressor Driver 5 x 106 NB4 cells were subcutaneously injected into the flank of 6-7-week-old female nude mice. The tumor number, body weight, and tumor volume were measured every other day. Tumor volumes were estimated using the following formula: tumor volume = (length x width2)/2. When tumor volumes reached 100-200 mm3, the mice were randomly divided into solvent control, RSL3, GSK3368715, or RSL3 + GSK3368715 combination groups (six mice per group). Specifically, for the RSL3 group, mice received intraperitoneal injections of RSL3 at 50 mg/kg 2 days apart. In the GSK3368715 group, GSK3368715 was intraperitoneally injected into mice at a dose of 75 mg/kg for 2 consecutive days per week. For the group that received RSL3 + GSK3368715 combination treatment, GSK3368715 (75 mg/kg) was administered by intraperitoneal injection for the first 2 days. Immediately thereafter, the mice received an intraperitoneal injection of RSL3 (50 mg/kg) 2 days apart. After 1 day of rest, the cycle was repeated until the end of the study on Day 21. Tumor volumes and body weights of the mice were measured and recorded every other day. REF001019 ICD-11: 2A60 Acute myeloid leukemia CELL00037; CELL00034; CELL00239; CELL00057 NB4; HEL; MOLM-13; ; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00802 Both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of Acute myeloid leukemia (AML) cells following GSK3368715 treatment. Overall, PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia. Inducer Down regulation Up regulation Down regulation Suppressor Driver 5 x 106 NB4 cells were subcutaneously injected into the flank of 6-7-week-old female nude mice. The tumor number, body weight, and tumor volume were measured every other day. Tumor volumes were estimated using the following formula: tumor volume = (length x width2)/2. When tumor volumes reached 100-200 mm3, the mice were randomly divided into solvent control, RSL3, GSK3368715, or RSL3 + GSK3368715 combination groups (six mice per group). Specifically, for the RSL3 group, mice received intraperitoneal injections of RSL3 at 50 mg/kg 2 days apart. In the GSK3368715 group, GSK3368715 was intraperitoneally injected into mice at a dose of 75 mg/kg for 2 consecutive days per week. For the group that received RSL3 + GSK3368715 combination treatment, GSK3368715 (75 mg/kg) was administered by intraperitoneal injection for the first 2 days. Immediately thereafter, the mice received an intraperitoneal injection of RSL3 (50 mg/kg) 2 days apart. After 1 day of rest, the cycle was repeated until the end of the study on Day 21. Tumor volumes and body weights of the mice were measured and recorded every other day. REF001019 ICD-11: 2A60 Acute myeloid leukemia CELL00037; CELL00034; CELL00239; CELL00057 NB4; HEL; MOLM-13; ; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00812 Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 ( MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF001027 ICD-11: 2A83.1 Multiple myeloma CELL00001; CELL00138; CELL00541 RPMI-8226 ; U266; AML-12 Ferroptosis (hsa04216) Cell ferroptosis
unique00812 Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 (MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF001027 ICD-11: 2A83.1 Multiple myeloma CELL00001; CELL00138; CELL00541 RPMI-8226 ; U266; AML-12 Ferroptosis (hsa04216) Cell ferroptosis
unique00811 Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 ( MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF001027 ICD-11: 2A83.1 Multiple myeloma CELL00001; CELL00138; CELL00541 RPMI-8226 ; U266; AML-12 Ferroptosis (hsa04216) Cell ferroptosis
unique00811 Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 (MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF001027 ICD-11: 2A83.1 Multiple myeloma CELL00001; CELL00138; CELL00541 RPMI-8226 ; U266; AML-12 Ferroptosis (hsa04216) Cell ferroptosis
unique00162 Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000215 ICD-11: 2A83.1 Multiple myeloma CELL00138; CELL00001 U266; RPMI8226 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00162 Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000215 ICD-11: 2A83.1 Multiple myeloma CELL00138; CELL00001 U266; RPMI8226 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00929 Artesunate induced ferroptosis in different types of Burkitt's lymphoma cells, and caused a significant ERS response in tumor cells. The activation of the ATF4-CHOP-CHAC1 pathway up-regulated the expression of CHAC1 and degraded intracellular GSH, thus weakening the ability of lymphoma cells to resist ferroptosis. Inducer Up regulation Up regulation Up regulation Driver Marker/Driver Four -week-old NOD/SCID mice were purchased from Chu Shang Technology (Kunming, China). CA-46 cells were collected and re-suspended in PBS at a concentration of 1-5 x 107 cells/mL. Totally, 0.2 mL cells were inoculated subcutaneously in the middle and posterior armpits of mice. When the transplanted tumor was established, the mice were injected the artesunate solution intraperitoneally in accordance with the body weight (200 mg/kg) daily. REF000096 ICD-11: 2A85 Burkitt lymphoma CELL00040; CELL00158 DAUDI; CA-46 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00929 Artesunate induced ferroptosis in different types of Burkitt's lymphoma cells, and caused a significant ERS response in tumor cells. The activation of the ATF4-CHOP-CHAC1 pathway up-regulated the expression of CHAC1 and degraded intracellular GSH, thus weakening the ability of lymphoma cells to resist ferroptosis. Inducer Up regulation Up regulation Up regulation Driver Marker/Driver Four -week-old NOD/SCID mice were purchased from Chu Shang Technology (Kunming, China). CA-46 cells were collected and re-suspended in PBS at a concentration of 1-5 x 107 cells/mL. Totally, 0.2 mL cells were inoculated subcutaneously in the middle and posterior armpits of mice. When the transplanted tumor was established, the mice were injected the artesunate solution intraperitoneally in accordance with the body weight (200 mg/kg) daily. REF000096 ICD-11: 2A85 Burkitt lymphoma CELL00040; CELL00158 DAUDI; CA-46 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00549 Kayadiol decreased the expression of SLC7A11 and GPX4, the negative regulatory proteins for ferroptosis. And p53 was the key mediator of kayadiol-induced ferroptosis by SLC7A11/GPX4 axis through p53 knockout experiments. Kayadiol can serve as an effective alternative in the treatment of NK/T cell lymphoma. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000769 ICD-11: 2B01 NK/T cell lymphoma CELL00232; CELL10093 YT; Peripheral blood lymphocytes (PBLs) Ferroptosis (hsa04216) Cell ferroptosis
unique01027 LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11). Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000241 ICD-11: 2B33 Myeloid leukaemia CELL00035; CELL00036 HL60; K562 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01027 LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11). Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000241 ICD-11: 2B33 Myeloid leukaemia CELL00035; CELL00036 HL60; K562 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00417 Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000563 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00094 MG63; HOS Ferroptosis (hsa04216) Cell ferroptosis
dupunique00417 Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000563 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00094 MG63; HOS Ferroptosis (hsa04216) Cell ferroptosis
unique01073 Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM ( SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000300 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00143; CELL00049 HT-1080; Calu-1; HeLa Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01073 Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM (SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000300 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00143; CELL00049 HT-1080; Calu-1; HeLa Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00219 Quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma. Inducer Up regulation Down regulation Down regulation Driver Suppressor Adult male athymic BALB/c nude mice (20-22 g of 5-week-old mice) were housed in a controlled environment at 23 ± 2 and 40%-70% humidity under a 12 h dark/light cycle with free access to irradiated food and sterile water. A suspension of 6 x 106/100 uL TCA-8113 cells was inoculated subcutaneously into the hind flank region of each nude mouse. The average tumor volume in nude mice reached 100 mm3, and mice were randomly divided into three groups. Quisinostat was formulated in normal saline and administered at 3 and 10 mg/kg/day byintraperitoneal injection. Control mice were given equal volume saline intraperitoneally. The tumor volume and the bodyweight of mice were monitored every three days. REF000280 ICD-11: 2B6E Tongue squamous cell carcinoma CELL00159; CELL00300 CAL-27; TCA-8113 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell proliferation; Cell apoptosis; Cell pyroptosis
unique00170 The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1( esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000225 ICD-11: 2B70 Esophageal cancer CELL00228 TE1 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00170 The levels of intracellular iron, malondialdehyde, and reactive oxygen species after oridonin (Ori) treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1(esophageal cancer cell) cell proliferation is associated with ferroptosis. Ori can inhibit the gamma-glutamyl cycle by inhibiting the activity of GGT1 and binding to cysteine, thereby inducing ferroptosis to exert anti-cancer activity. Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000225 ICD-11: 2B70 Esophageal cancer CELL00228 TE1 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00960 Cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in gastric cancer. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Male nude mice (BALB/c-nu, 6B8 weeks) were housed in a pathogen free animal facility with access to water and food, and allowed to eat and drink adlibitum. 5 x 105 SGC7901 cells and CAFs were injected subcutaneously for one mouse. These tumor-implanted mice were injected with either cisplatin (5 ug/g) or saline every 5 days since the day ten, and were sacrificed and tumors were removed at the 30th Day. REF000137 ICD-11: 2B72 Gastric cancer CELL00124; CELL00290; CELL00114 SGC7901; MGC803; MKN45 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00961 Cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in gastric cancer. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Male nude mice (BALB/c-nu, 6B8 weeks) were housed in a pathogen free animal facility with access to water and food, and allowed to eat and drink adlibitum. 5 x 105 SGC7901 cells and CAFs were injected subcutaneously for one mouse. These tumor-implanted mice were injected with either cisplatin (5 ug/g) or saline every 5 days since the day ten, and were sacrificed and tumors were removed at the 30th Day. REF000137 ICD-11: 2B72 Gastric cancer CELL00124; CELL00290; CELL00114 SGC7901; MGC803; MKN45 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00961 Cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in gastric cancer. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Male nude mice (BALB/c-nu, 6B8 weeks) were housed in a pathogen free animal facility with access to water and food, and allowed to eat and drink adlibitum. 5 x 105 SGC7901 cells and CAFs were injected subcutaneously for one mouse. These tumor-implanted mice were injected with either cisplatin (5 ug/g) or saline every 5 days since the day ten, and were sacrificed and tumors were removed at the 30th Day. REF000137 ICD-11: 2B72 Gastric cancer CELL00124; CELL00290; CELL00114 SGC7901; MGC803; MKN45 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00960 Cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in gastric cancer. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Male nude mice (BALB/c-nu, 6B8 weeks) were housed in a pathogen free animal facility with access to water and food, and allowed to eat and drink adlibitum. 5 x 105 SGC7901 cells and CAFs were injected subcutaneously for one mouse. These tumor-implanted mice were injected with either cisplatin (5 ug/g) or saline every 5 days since the day ten, and were sacrificed and tumors were removed at the 30th Day. REF000137 ICD-11: 2B72 Gastric cancer CELL00124; CELL00290; CELL00114 SGC7901; MGC803; MKN45 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01084 Apatinib exerted antitumor effects against gastric cancer cells in vitro and in vivo through the induction of lipid peroxidation mediated by GPX4, then lead to ferroptosis. Furethermore, we found apatinib inhibited transcription of GPX4 via a SREBP1a-mediated pathway. These results indicated that GPX4 may be a potential target for anti-GC efficacy evaluation and treatment of apatinib. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female nude mice (BALB/c, nu/nu, 18-22 g, 4-5 weeks old) were obtained from Guangdong Medical Laboratory Animal center, China, and maintained under specific pathogen-free conditions on a 12h/12h light/dark cycle. Each mouse was injected subcutaneously with eight million luciferase-expressing cells resuspended in 50 ul of PBS and 50 ul of Matrigel (BD Biosciences). When a palpable mass had developed, the mice were randomly divided into five groups: apatinib (50 mg/kg/day oral dose for 14 days); RSL3 (100 mg/kg injection of RSL3 twice per week for 2 weeks at the same site); both; apatinib (50 mg/kg/day oral dose for 14 days) plus vitamin E (100 mg/kg/day oral dose for 14 days); and vehicle (DMSO, 100 ul oral dose for 14 days). REF000314 ICD-11: 2B72 Gastric cancer CELL00290; CELL00114; CELL00261; CELL00124; CELL00071 MGC803; MKN45; BGC823; SGC7901; AGS Fatty acid metabolism (hsa01212); Glutathione metabolism (hsa00480) Cell ferroptosis
unique01084 Apatinib exerted antitumor effects against gastric cancer cells in vitro and in vivo through the induction of lipid peroxidation mediated by GPX4, then lead to ferroptosis. Furethermore, we found apatinib inhibited transcription of GPX4 via a SREBP1a-mediated pathway. These results indicated that GPX4 may be a potential target for anti-GC efficacy evaluation and treatment of apatinib. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female nude mice (BALB/c, nu/nu, 18-22 g, 4-5 weeks old) were obtained from Guangdong Medical Laboratory Animal center, China, and maintained under specific pathogen-free conditions on a 12h/12h light/dark cycle. Each mouse was injected subcutaneously with eight million luciferase-expressing cells resuspended in 50 ul of PBS and 50 ul of Matrigel (BD Biosciences). When a palpable mass had developed, the mice were randomly divided into five groups: apatinib (50 mg/kg/day oral dose for 14 days); RSL3 (100 mg/kg injection of RSL3 twice per week for 2 weeks at the same site); both; apatinib (50 mg/kg/day oral dose for 14 days) plus vitamin E (100 mg/kg/day oral dose for 14 days); and vehicle (DMSO, 100 ul oral dose for 14 days). REF000314 ICD-11: 2B72 Gastric cancer CELL00290; CELL00114; CELL00261; CELL00124; CELL00071 MGC803; MKN45; BGC823; SGC7901; AGS Fatty acid metabolism (hsa01212); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00320 Levobupivacaine-upregulated miR-489-3p enhanced ferroptosis of gastric cancer cells by targeting SLC7A11. MiR-489-3p was involved in levobupivacaine-induced ferroptosis of gastric cancer cells. Levobupivacaine/miR-489-3p/SLC7A11 axis attenuates gastric cancer cell proliferationin vitro. Inducer Up regulation Down regulation Down regulation Driver Suppressor Ten SCID nude mice aged 6-8 weeks were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China), and subcutaneously injected with SGC7901 cells (5 x 106 cells per mouse) in left back. One week after feeding, the mice were randomly divided into two groups, the control and treatment group. For the next 25 days, the mice in treatment group were injected with erastin (15 mg/kg intraperitoneally) or co-treated with 40 mol/kg body weight of levobupivacaine once a day. The body weight and tumor size were measured every 3 days. REF000442 ICD-11: 2B72 Gastric cancer CELL00322; CELL00174; CELL00124 GES-1; HGC27; SGC7901 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00320 Levobupivacaine-upregulated miR-489-3p enhanced ferroptosis of gastric cancer cells by targeting SLC7A11. MiR-489-3p was involved in levobupivacaine-induced ferroptosis of gastric cancer cells. Levobupivacaine/miR-489-3p/SLC7A11 axis attenuates gastric cancer cell proliferationin vitro. Inducer Up regulation Down regulation Down regulation Driver Suppressor Ten SCID nude mice aged 6-8 weeks were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China), and subcutaneously injected with SGC7901 cells (5 x 106 cells per mouse) in left back. One week after feeding, the mice were randomly divided into two groups, the control and treatment group. For the next 25 days, the mice in treatment group were injected with erastin (15 mg/kg intraperitoneally) or co-treated with 40 mol/kg body weight of levobupivacaine once a day. The body weight and tumor size were measured every 3 days. REF000442 ICD-11: 2B72 Gastric cancer CELL00322; CELL00174; CELL00124 GES-1; HGC27; SGC7901 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00155 Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT (SLC7A11) expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Suppressor All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 106 BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points. REF000207 ICD-11: 2B72 Gastric cancer CELL00261; CELL00023 BGC-823; NCI-H87 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00864 BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/ AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma. Inducer Up regulation Down regulation Down regulation Driver Suppressor To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female). REF000045 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00120; CELL00095; CELL00143; CELL00049; CELL00057 HCT116; PANC1; HT1080; Calu-1; HeLa; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00864 BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma. Inducer Up regulation Down regulation Down regulation Driver Suppressor To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female). REF000045 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00120; CELL00095; CELL00143; CELL00049; CELL00057 HCT116; PANC1; HT1080; Calu-1; HeLa; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00082 Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF000135 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00056; CELL00125; CELL00095 HCT116; H1299; SK-Hep1; HT-1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00083 Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF000135 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00056; CELL00125; CELL00095 HCT116; H1299; SK-Hep1; HT-1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00082 Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF000135 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00056; CELL00125; CELL00095 HCT116; H1299; SK-Hep1; HT-1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00083 Inhibition of MDM2 (Nutlin-3) or MDMX (NCS207895) leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis in Colon carcinoma. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF000135 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00056; CELL00125; CELL00095 HCT116; H1299; SK-Hep1; HT-1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01089 ACSL4, a vital regulator of ferroptosis, could interact with ELOVL6 directly. Apatinib promoted ferroptosis in colorectal cancer (CRC) cells by targeting ELOVL6/ACSL4, providing a new mechanism support for apatinib application in the clinical treatment of CRC. Inducer Down regulation Up regulation Down regulation Suppressor Driver . REF000328 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00307 HCT116; HIEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00873 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00872 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00870 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00871 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00875 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00869 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00874 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01089 ACSL4, a vital regulator of ferroptosis, could interact with ELOVL6 directly. Apatinib promoted ferroptosis in colorectal cancer (CRC) cells by targeting ELOVL6/ACSL4, providing a new mechanism support for apatinib application in the clinical treatment of CRC. Inducer Down regulation Up regulation Down regulation Suppressor Driver . REF000328 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00307 HCT116; HIEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00875 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00874 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00873 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00872 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00871 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00870 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00869 Elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2cells compared to in DLD-1 cells potentially targeted ACSL-4 and resulted in suppression of ACSL-4. Overall, bromelain inhibits proliferation of Kras mutant Colorectal Cancer (CRC) effectively via ACSL-4. Inducer Down regulation Up regulation Down regulation Suppressor Driver Animals (n = 7) were given 2.5% DSS in drinking water for 5 days and then no treatment for 14 days as one cycle; this process was repeated for three cycles. In the last cycle, 2% DSS water treated to each group and no treatment for 14 days. During the three DSS cycle, 3 mg/kg bromelain were injected daily intraperitoneally and colon and spleen tissues were harvested after three DSS cycle in 57 days to study polyp burden and to perform histological staining. REF000054 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00087; CELL10055; CELL00083; CELL10054; CELL00409 NCI-H508; HCT116; G13D; DLD1; G12D; CRL-1459 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00653 Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000882 ICD-11: 2B91 Colorectal cancer CELL00250 HCT-8 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00652 Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/ mTOR signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000882 ICD-11: 2B91 Colorectal cancer CELL00250 HCT-8 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00654 Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/ Akt/mTOR signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000882 ICD-11: 2B91 Colorectal cancer CELL00250 HCT-8 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00653 Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000882 ICD-11: 2B91 Colorectal cancer CELL00250 HCT-8 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00652 Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000882 ICD-11: 2B91 Colorectal cancer CELL00250 HCT-8 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00654 Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000882 ICD-11: 2B91 Colorectal cancer CELL00250 HCT-8 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01325 Our work reveals that cetuximab enhances the cytotoxic effect of RSL3 on KRAS mutant Colorectal cancer (CRC) cells and that cetuximab enhances RSL3-induced ferroptosis by inhibiting the Nrf2/HO-1 axis through the activation of p38 MAPK. Inducer Up regulation Down regulation Down regulation Driver Suppressor The DLD-1 cell suspension (4 x 106 cells/200 ul) was injected subcutaneously into the right dorsal flank of 5-week-old male BALB/c nude mice (Charles River, China). The mice were randomly divided into four groups (5 mice/group): 1) the control group, 2) the RSL3 group, 3) the cetuximab group, and 4) the RSL3 + cetuximab group. Both RSL3 (5 mg/kg) and cetuximab (13 mg/kg) were administered by intraperitoneal injection in a volume of 100 ul once per day. The tumour volume was calculated as 0.5 x length x width2. After 17 days of treatment, the mice were sacrificed, and the tumours were removed. Then, tumour tissue obtained from the different treated groups was subjected to western blotting and immunohistochemical experiments. REF000580 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00083; CELL00109; CELL00018 HCT116; DLD-1; LOVO; SW480 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01325 Our work reveals that cetuximab enhances the cytotoxic effect of RSL3 on KRAS mutant Colorectal cancer (CRC) cells and that cetuximab enhances RSL3-induced ferroptosis by inhibiting the Nrf2/HO-1 axis through the activation of p38 MAPK. Inducer Up regulation Down regulation Down regulation Driver Suppressor The DLD-1 cell suspension (4 x 106 cells/200 ul) was injected subcutaneously into the right dorsal flank of 5-week-old male BALB/c nude mice (Charles River, China). The mice were randomly divided into four groups (5 mice/group): 1) the control group, 2) the RSL3 group, 3) the cetuximab group, and 4) the RSL3 + cetuximab group. Both RSL3 (5 mg/kg) and cetuximab (13 mg/kg) were administered by intraperitoneal injection in a volume of 100 ul once per day. The tumour volume was calculated as 0.5 x length x width2. After 17 days of treatment, the mice were sacrificed, and the tumours were removed. Then, tumour tissue obtained from the different treated groups was subjected to western blotting and immunohistochemical experiments. REF000580 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00083; CELL00109; CELL00018 HCT116; DLD-1; LOVO; SW480 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00743 Ibrutinib inhibited BTK, which prevented Nrf2 translocating to cell nucleus and the activation of the Nrf2 dependent antioxidant genes during oxidative stress conditions and eventually enhanced the sensitivity of Colorectal cancer (CRC) cells to ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor Sixty mice were randomly divided into six groups, (1) the CRC model group (model), (2) mice with RSL3 treatment, (3) mice with Erastin treatment, (4) mice with Ibrutinib treatment, (5) mice with RSL3 and Ibrutinib treatment, and (6) Erastin and Ibrutinib group. Murine subcutaneous tumor model and xenograft tumor mouse model were established and please refer to supplemental method for details. For CRC model group, the mice were treated with PBS for two weeks. For RSL3 group, the mice were intraperitoneal injected with RSL3 (5 mg/kg daily) for two weeks. For Erastin group, the mice were intraperitoneal injected with Erastin (30 mg/kg, twice every other day) for two weeks. For Ibrutinib treatment group, mice were administered in drinking water at a concentration of 0.16 mg/ml for two weeks. Mice were also treated in combination with RSL and Ibrutinib or Erastin and Ibrutinib. REF000968 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00109; CELL00370; CELL00087; CELL00018; CELL00133; CELL00132; CELL00083; CELL00096; CELL00046 NCI-H508; LoVo; LS513; HCT116; SW480; SW620; SW1116; DLD-1; HT-29; Caco-2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01324 Our work reveals that cetuximab enhances the cytotoxic effect of RSL3 on KRAS mutant Colorectal cancer (CRC) cells and that cetuximab enhances RSL3-induced ferroptosis by inhibiting the Nrf2/HO-1 axis through the activation of p38 MAPK. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor The DLD-1 cell suspension (4 x 106 cells/200 ul) was injected subcutaneously into the right dorsal flank of 5-week-old male BALB/c nude mice (Charles River, China). The mice were randomly divided into four groups (5 mice/group): 1) the control group, 2) the RSL3 group, 3) the cetuximab group, and 4) the RSL3 + cetuximab group. Both RSL3 (5 mg/kg) and cetuximab (13 mg/kg) were administered by intraperitoneal injection in a volume of 100 ul once per day. The tumour volume was calculated as 0.5 x length x width2. After 17 days of treatment, the mice were sacrificed, and the tumours were removed. Then, tumour tissue obtained from the different treated groups was subjected to western blotting and immunohistochemical experiments. REF000580 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00083; CELL00109; CELL00018 HCT116; DLD-1; LOVO; SW480 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01324 Our work reveals that cetuximab enhances the cytotoxic effect of RSL3 on KRAS mutant Colorectal cancer (CRC) cells and that cetuximab enhances RSL3-induced ferroptosis by inhibiting the Nrf2/HO-1 axis through the activation of p38 MAPK. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor The DLD-1 cell suspension (4 x 106 cells/200 ul) was injected subcutaneously into the right dorsal flank of 5-week-old male BALB/c nude mice (Charles River, China). The mice were randomly divided into four groups (5 mice/group): 1) the control group, 2) the RSL3 group, 3) the cetuximab group, and 4) the RSL3 + cetuximab group. Both RSL3 (5 mg/kg) and cetuximab (13 mg/kg) were administered by intraperitoneal injection in a volume of 100 ul once per day. The tumour volume was calculated as 0.5 x length x width2. After 17 days of treatment, the mice were sacrificed, and the tumours were removed. Then, tumour tissue obtained from the different treated groups was subjected to western blotting and immunohistochemical experiments. REF000580 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00083; CELL00109; CELL00018 HCT116; DLD-1; LOVO; SW480 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00743 Ibrutinib inhibited BTK, which prevented Nrf2 translocating to cell nucleus and the activation of the Nrf2 dependent antioxidant genes during oxidative stress conditions and eventually enhanced the sensitivity of Colorectal cancer (CRC) cells to ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor Sixty mice were randomly divided into six groups, (1) the CRC model group (model), (2) mice with RSL3 treatment, (3) mice with Erastin treatment, (4) mice with Ibrutinib treatment, (5) mice with RSL3 and Ibrutinib treatment, and (6) Erastin and Ibrutinib group. Murine subcutaneous tumor model and xenograft tumor mouse model were established and please refer to supplemental method for details. For CRC model group, the mice were treated with PBS for two weeks. For RSL3 group, the mice were intraperitoneal injected with RSL3 (5 mg/kg daily) for two weeks. For Erastin group, the mice were intraperitoneal injected with Erastin (30 mg/kg, twice every other day) for two weeks. For Ibrutinib treatment group, mice were administered in drinking water at a concentration of 0.16 mg/ml for two weeks. Mice were also treated in combination with RSL and Ibrutinib or Erastin and Ibrutinib. REF000968 ICD-11: 2B91 Colorectal cancer CELL00380; CELL00109; CELL00370; CELL00087; CELL00018; CELL00133; CELL00132; CELL00083; CELL00096; CELL00046 NCI-H508; LoVo; LS513; HCT116; SW480; SW620; SW1116; DLD-1; HT-29; Caco-2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01618 Niraparib, a widely used PARPi, augmented cGAS-mediated ferroptosis and immune activation. In colorectal cancer models, cGAS signaling exerts tumor control via ATF3SLC7A11GPX4-mediated ferroptosis and IFNCD8 T cell-mediated antitumor immune response. Inducer Up regulation Down regulation Down regulation Driver Suppressor Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed. REF000833 ICD-11: 2B91 Colorectal cancer CELL00562; CELL00561; CELL00318 HT29; CT26; MC38 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cytosolic DNA-sensing pathway (hsa04623) Cell ferroptosis
unique01725 Sodium butyrate (NaB) induces ferroptosis in colorectal cancer cells through the CD44/SLC7A11 signaling pathway and has synergistic effects with Erastin. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Six-week-old male C57BL/6J mice were purchased from the Medical Laboratory Animal Center of Guangdong Province (Foshan, China). Forty-five C57BL/6L mice were randomized into 4 groups after 1 week of adaptive feeding: (1) Control group (n = 9); (2) AOM/DSS group (n = 12); (3) AOM/DSS + NaB (orally) group (n = 12); 4) AOM/DSS + NaB (intraperitoneal injection) group (n = 12). The Control group received an intraperitoneal injection of saline solution beginning on day 1, and received sterile drinking water throughout the study. Other three groups received an intraperitoneal injection of 10 mg/kg AOM (Sigma Aldrich) beginning on day 1, and received drinking water containing 2.5% DSS at the second and eighth weeks (2% DSS in the fifth week). Besides, 0.1 M NaB (Sigma Aldrich) was given in drinking water during the whole experiment process in AOM/DSS + NaB (p.o.) group, while AOM/DSS + NaB (i.p.) group was injected intraperitoneally (IP) with 1 g/kg NaB per day. REF000946 ICD-11: 2B91 Colorectal cancer CELL00267; CELL00087 Normal human colon epithelial cell FHC; HCT-116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01725 Sodium butyrate (NaB) induces ferroptosis in colorectal cancer cells through the CD44/SLC7A11 signaling pathway and has synergistic effects with Erastin. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Six-week-old male C57BL/6J mice were purchased from the Medical Laboratory Animal Center of Guangdong Province (Foshan, China). Forty-five C57BL/6L mice were randomized into 4 groups after 1 week of adaptive feeding: (1) Control group (n = 9); (2) AOM/DSS group (n = 12); (3) AOM/DSS + NaB (orally) group (n = 12); 4) AOM/DSS + NaB (intraperitoneal injection) group (n = 12). The Control group received an intraperitoneal injection of saline solution beginning on day 1, and received sterile drinking water throughout the study. Other three groups received an intraperitoneal injection of 10 mg/kg AOM (Sigma Aldrich) beginning on day 1, and received drinking water containing 2.5% DSS at the second and eighth weeks (2% DSS in the fifth week). Besides, 0.1 M NaB (Sigma Aldrich) was given in drinking water during the whole experiment process in AOM/DSS + NaB (p.o.) group, while AOM/DSS + NaB (i.p.) group was injected intraperitoneally (IP) with 1 g/kg NaB per day. REF000946 ICD-11: 2B91 Colorectal cancer CELL00267; CELL00087 Normal human colon epithelial cell FHC; HCT-116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01618 Niraparib, a widely used PARPi, augmented cGAS-mediated ferroptosis and immune activation. In colorectal cancer models, cGAS signaling exerts tumor control via ATF3SLC7A11GPX4-mediated ferroptosis and IFNCD8 T cell-mediated antitumor immune response. Inducer Up regulation Down regulation Down regulation Driver Suppressor Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed. REF000833 ICD-11: 2B91 Colorectal cancer CELL00562; CELL00561; CELL00318 HT29; CT26; MC38 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cytosolic DNA-sensing pathway (hsa04623) Cell ferroptosis
unique01497 The expressions of FAM98A and SLC7A11 were also downregulated after metformin treatment. And FAM98A is predominantly expressed in the colorectal cancer tissues and high FAM98A expression is usually accompanied by the high expression of SLC7A11, which usually means ferroptosis resistance. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor A total 1 x 106 SW620-vector or SW620-FAM98A cells were suspended in 100 ul PBS and injected s.c. into the back of 4- to 6-week-old male BALB/cnude mice (Laboratory Animal Unit, Southern Medical University, China). The sizes of the resulting tumors were measured weekly. Tumor volumes were calculated as follows: total tumor volume (mm3) = (Length x Width2)/2, where Length is the longest length. When the tumor sizes reached about 200 mm3, nude mice in the four groups were given PBS or 5-FU treatment (30 mg/kg, intraperitoneal injection, twice a week), respectively. Nude mice were maintained in a barrier facility in racks filtered with a high-efficiency particulate air filter. REF000719 ICD-11: 2B91 Colorectal cancer CELL00122; CELL00018; CELL00133; CELL00109; CELL00046; CELL00088; CELL00083; CELL00267 RKO; SW480; SW620; LOVO; Caco-2; HCT15; DLD-1; FHC Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00403 Inhibition of CBR1 by chrysin increased cellular ROS levels and led to ROS-dependent autophagy, which resulted in the degradation of ferritin heavy polypeptide 1 (FTH1) and an increase in the intracellular free iron level that participates in ferroptosis in pancreatic cancer (PC) cells. Finally, chrysin enhanced PC sensitivity to gemcitabine by inducing ferroptotic death in vitro and in vivo.? Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor Male BALB/c nude mice (5 weeks old, weighing 18-20 g) were provided by Jiangsu Jicui Yaokang Biotechnology Co., Ltd. (Nanjing, China). The mice were subcutaneously transplanted with non-targeting shRNA (shcontrol) or CBR1-targeting shRNA (shCBR1)-transfected PANC-1 cells (200 uL, 1 x 107 cells). Tumor volumes and body weights were measured every 4 days (n = 4, each), tumor volume = 0.5 x (a x a x b) (a, smallest diameter; b, largest diameter). The mice were subcutaneously inoculated with PANC-1 cells (200 uL, 1 x 107 cells) in the combination treatment. When the tumor volume reached 80-100 mm3, the mice were treated with chrysin (30 mg/kg/i.P., daily), gemcitabine (20 mg/kg/i.p., once every other day), or in combination for four weeks. REF000554 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00047; CELL00008; CELL00073 PANC-1; Capan-2; BxPC-3; AsPC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell proliferation; Cell autophagy
unique01191 SMG9, a component of the NMD machinery, is a selective driver for ferroptosis in pancreatic cancer cells. SMG9 is a direct binding protein of GPX4 to promote the degradation of GPX4 in response to RSL3 (a GPX4 inhibitor), but not erastin (a SLC7A11 inhibitor). Inducer Up regulation Down regulation Down regulation Driver Suppressor To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and then given intratumoral treatment with RSL3 (50 mg/kg, once every other day) at day 7 for 2 weeks. REF000435 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00095 PANC1; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00567 The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice. Inducer . Up regulation Up regulation Driver Driver All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 105 cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm3, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. REF000797 ICD-11: 2C10 Pancreatic cancer CELL00233; CELL00008; CELL00120; CELL10119; CELL00025 PaTu8988; BxPC3; PANC1; MEFs; Panc02 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00566 The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice. Inducer . Up regulation Up regulation Driver Marker/Suppressor All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 105 cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm3, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days. REF000797 ICD-11: 2C10 Pancreatic cancer CELL00233; CELL00008; CELL00120; CELL10119; CELL00025 PaTu8988; BxPC3; PANC1; MEFs; Panc02 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01508 Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor For xenograft assays, we subcutaneously injected 1 x 106 PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment. REF000728 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00160 PANC-1; CFPAC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01509 Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor For xenograft assays, we subcutaneously injected 1 x 106 PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment. REF000728 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00160 PANC-1; CFPAC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01715 The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pancreatic neuroendocrine tumors (pNETs) that targets mTOR signaling. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000933 ICD-11: 2C10.1 Pancreatic neuroendocrine tumor CELL00276; CELL00258 BON-1; QGP-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01063 Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable. REF000282 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00029; CELL00057; CELL00304; CELL00048; CELL00098; CELL00012 CAF; 293T; 7702; HepG2; Hep3B; Huh-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique01384 Sorafenib treatment triggered ferroptosis via lipid ROS production and chelatable iron accumulation. The ETS1 upregulated by sorafenib was a key transcription factor of miR-23a-3p that directly enhanced miR-23a-3p expression. MiR-23a-3p recognized and bound to ACSL4 3UTR to limit lipid ROS production, thus attenuating sorafenib-induced ferroptotic cell death in hepatocellular carcinoma. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Parental MHCC97L cells (2 x 106 cells/mouse) were subcutaneously injected into the 4-to-5-week-old NOD-SCID mice. When the tumours reached a volume of around 50-100 mm3 (calculated by the formula 4/3(D/2)(d/2)2, where D and d represent the minor and major axis of the tumour, respectively), the maximum tolerated dose of sorafenib (50 mg/kg) was given to the mice by oral gavage daily until the drug resistance occurred, denoted as the drug resistant group. For the control, the wild type group was treated with the vehicle (0.5% CMC-Na). The tumour size and body weight were measured every 3 days. REF000632 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00447; CELL00016; CELL00484 MHCC97L; PLC/PRF/5; 293FT Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01385 Sorafenib treatment triggered ferroptosis via lipid ROS production and chelatable iron accumulation. The ETS1 upregulated by sorafenib was a key transcription factor of miR-23a-3p that directly enhanced miR-23a-3p expression. MiR-23a-3p recognized and bound to ACSL4 3UTR to limit lipid ROS production, thus attenuating sorafenib-induced ferroptotic cell death in hepatocellular carcinoma. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Parental MHCC97L cells (2 x 106 cells/mouse) were subcutaneously injected into the 4-to-5-week-old NOD-SCID mice. When the tumours reached a volume of around 50-100 mm3 (calculated by the formula 4/3(D/2)(d/2)2, where D and d represent the minor and major axis of the tumour, respectively), the maximum tolerated dose of sorafenib (50 mg/kg) was given to the mice by oral gavage daily until the drug resistance occurred, denoted as the drug resistant group. For the control, the wild type group was treated with the vehicle (0.5% CMC-Na). The tumour size and body weight were measured every 3 days. REF000632 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00447; CELL00016; CELL00484 MHCC97L; PLC/PRF/5; 293FT Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00922 S1R (TMBIM4) protects hepatocellular carcinoma cells against sorafenib and subsequent ferroptosis. Inhibition of S1R by RNAi and antagonists markedly increased the anticancer activity of sorafenib by modulating the expression of GPX4, iron metabolism and ROS. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor To generate murine subcutaneous tumours, 1 x 107 control shRNA or S1R-knockdown Huh7 cells in 200 uL of PBS were injected subcutaneously to the right of the dorsal midline. At day seven, the mice were randomly divided into groups and treated with sorafenib (10 mg/kg/intraperitoneal injection (i.p.), once every other day) for 2 weeks. On day 28, tumours were removed. REF000090 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012; CELL00017; CELL00016 Hep G2; Huh7; SMMC7721; PLC/PRF/5 Ferroptosis (hsa04216) Cell ferroptosis
unique01261 LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of liver cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor BALB/c nude mice (age 6 weeks) were brought from the Laboratory Animal Center of Chinese Academy of Sciences (China). HepG2 cell suspension (100 uL, 5 x 105 per site) was hypodermically inoculated into the fat pad of mice. Tumor volume was calculated as follows: tumor volume (mm3) = 0.5 x width (mm)2 x length (mm). When tumor size reached 100 mm3, mice were treated with ketamine (20 mg/kg) or saline intraperitoneally. The mice were succumbed to death when tumor size reached 1000 mm3. Tumors were isolated and weighted. All animal experiments were carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978). REF000511 ICD-11: 2C12 Hepatocellular carcinoma CELL00048; CELL00012 HepG2; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01262 LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of liver cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis. Inducer Up regulation Down regulation Down regulation Driver Suppressor BALB/c nude mice (age 6 weeks) were brought from the Laboratory Animal Center of Chinese Academy of Sciences (China). HepG2 cell suspension (100 uL, 5 x 105 per site) was hypodermically inoculated into the fat pad of mice. Tumor volume was calculated as follows: tumor volume (mm3) = 0.5 x width (mm)2 x length (mm). When tumor size reached 100 mm3, mice were treated with ketamine (20 mg/kg) or saline intraperitoneally. The mice were succumbed to death when tumor size reached 1000 mm3. Tumors were isolated and weighted. All animal experiments were carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978). REF000511 ICD-11: 2C12 Hepatocellular carcinoma CELL00048; CELL00012 HepG2; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01386 The depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat Hepatocellular carcinoma in vitro and in vivo. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female Nod-SCID mice of 6-8 weeks old were purchased from HFK BIOSCIENCE (Beijing). Hep3B-vehicle/Hep3B-PSTK-KO cells were harvested and injected subcutaneously (1 x 107 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into four groups and injected intraperitoneally with Abemaciclib (50 mg/kg, every other day) or vehicle. Mice were sacrificed when the tumor volume exceeded 2000 mm3. PSTK-KO or vehicle Hep3B cells were implanted and treated with Sorafenib (50 mg/kg, every other day) or Erastin (50 mg/kg, every other day) for 42 days. Tumor volumes were monitored and quantified by the modified ellipsoidal formula, tumor volume = (length x width2)/2. To check the efficacities and appraisal the side effects of PSTK inhibitors, Hep3B cells were harvested and in injected subcutaneously (5 x 106 cells in 200 uL PBS) into Nod-SCID mice (upper flank). Treatments were started when tumor volumes reached around 50 mm3. Included mice were randomly divided into six groups and intragastrically treated with Punicalin (100 mg/kg, every day), Geraniin (100 mg/kg, every day), Sorafenib (50 mg/kg, every day) with or without PSTK inhibitors (Punicalin/Geraniin) for 30 days. Tumor volumes and mice weights were measured every three days. REF000633 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00098; CELL00048; CELL00125; CELL00016; CELL00084; CELL00063; CELL00061; CELL00140; CELL10037; CELL00253; CELL00255; CELL00012; CELL00275 Hep3B; HepG2; SK-HEP-1; PLC/PRF/5; SNU-387; SNU-182; SNU-398; WRL68; HUVECs; JHH2; JHH7; Huh7; Li-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01586 LINC01134 was positively correlated with GPX4 or Nrf2, demonstrating the clinical significance of LINC01134, Nrf2 and GPX4 in OXA resistance of hepatocellular carcinoma (HCC). Silenced LINC01134 enhances Oxaliplatin sensitivity by facilitating ferroptosis through GPX4 in hepatocarcinoma. . . . Up regulation Suppressor Suppressor . REF000789 ICD-11: 2C12.02 Hepatocarcinoma CELL00048; CELL00012 HepG2; Huh-7 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01742 HCG18 sponged miR-450b-5p to regulate GPX4. Collectively, Silencing HCG18 inhibits GPX4 by binding to miR-450b-5p, promotes GPX4-inhibited ferroptosis, and averts sorafenib resistance in hepatocellular carcinoma (HCC). Silencing HCG18 inhibited cell proliferation, promoted apoptosis, and impaired sorafenib resistance. . . . Up regulation Suppressor Suppressor BALB/c nude mice (4-6 weeks old) from Beijing Vital River Laboratory Animal Technology (Beijing, China) were reared in a standard laboratory with free access to food and water. Lentivirus LV-sh-NC and LV-sh-HCG18 were from GenePharma (Shanghai, China). In order to establish subcutaneous xenograft tumor models, Huh7-SR cells were infected with lentivirus LV-sh-NC or LV-sh-HCG18 and then resuspended in PBS at 5 x 105/mL. Totally 100 uL cells were subcutaneously injected into the right dorsal area of each nude mouse. When the tumor volume reached 150 mm3, sorafenib (10 mg/kg) was orally administered to nude mice once a day to the end. Tumor volume (V) was calculated: V = 0.5 x L x W2, where L and W were defined as tumor length (L) and width (W). After 28 days of cell injection, the nude mice were euthanized by intraperitoneal injection of excessive pentobarbital sodium (100 mg/kg). REF000963 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00125; CELL00048; CELL00299; CELL00012; CELL00304 SK-hep1; HepG2; HCCLM3; Huh7; LO2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00537 Withaferin A may attenuate the metastatic potential and sorafenib resistance by regulating Keap1/Nrf2-associated EMT and ferroptosis. Thus, Withaferin A may serve as a promising agent for Hepatocellular carcinoma therapy, especially for advanced hepatocellular carcinoma. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000743 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00116; CELL00304 HepG2; SNU449; HL-7702 Pathways in cancer (hsa05200); Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell proliferation; Cell invasion
unique00724 Tiliroside directly binds to TBK1 and inhibits its activity, which inhibits the phosphorylation of Ser349 on p62. Consequently, this decreases the affinity of p62 for Keap1, promotes ubiquitination and degradation of Nrf2 and ferroptosis, and eventually increases the sensitivity of hepatocellular carcinoma cells to sorafenib. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor All animal studies were approved by the Committee on Ethics of Animal Experiments of Binzhou Medical University (approval no: BZMU-IACUC-2021-331, date: 09/10/2021). To generate the ectopic HCC mouse models, HepG2-luciferase cells (HepG2 cells transfected with luciferase gene) were suspended in serum-free media and matrigel (BD Biosciences) at a ratio of 1:1 v/v. A total of 2.5 x 106 HepG2-luciferase cells/100 ul were injected into the left axilla of mice. After reaching a tumor size of 100-150 mm3, all mice were randomly divided into four groups: control (vehicle, intraperitoneal [i.p.]), tiliroside (20 mg/kg,i.p.), sorafenib (30 mg/kg,i.p.), or combination treatment (tiliroside and sorafenib,i.p.). All treatments were administered every 3 d, and the length and width of tumor were measured every 4 d. The formula tumor volume = (length x width2)/2 was used to calculate the tumor volume. Body weight was recorded every 7 d, and the morphology of the tumor was photographed using animal in vivo imaging technology (IVIS Spectrum; PerkinElmer) before the day of sacrifice. The mice were sacrificed 40 d after administration, and the tumors were dissected and weighed. The major organs and xenograft tumors were fixed with 4% paraformaldehyde. REF000942 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00098; CELL00017; CELL00304 HepG2; Hep3B; SMMC-7721; the normal hepatocyte cell line L02 Ferroptosis (hsa04216) Cell ferroptosis
unique00827 Upon exposure to ferroptosis-inducing compounds (e.g., erastin, sorafenib, and buthionine sulfoximine), p62 (SQSTM1) expression prevented NRF2 degradation and enhanced subsequent NRF2 nuclear accumulation through inactivation of Kelch-like ECH-associated protein 1. The status of NRF2 is a key factor that determines the therapeutic response to ferroptosis-targeted therapies in hepatocellular carcinoma cells. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor To generate murine subcutaneous tumors, 1 x 106 Hepa16 cells in control shRNA or NRF2 knockdown cells in 200 ul phosphate buffered saline were injected subcutaneously to the right of the dorsal midline in C57BL/6 mice. Once the tumors reached 80-100 mm3 at day seven, mice were randomly allocated into groups and treated with erastin (30 mg/kg intraperitoneal injection [i.p.], twice every other day) and sorafenib (10 mg/kg i.p., once every other day) for two weeks. REF000008 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00009; CELL00098; CELL00098 HepG2; Hepa16; Hep3B; Hep3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01585 LINC01134 was positively correlated with GPX4 or Nrf2, demonstrating the clinical significance of LINC01134, Nrf2 and GPX4 in OXA resistance of hepatocellular carcinoma. Silenced LINC01134 enhances Oxaliplatin sensitivity by facilitating ferroptosis through GPX4 in hepatocarcinoma. . . . Up regulation Suppressor Marker/Suppressor . REF000789 ICD-11: 2C12.02 Hepatocarcinoma CELL00048; CELL00012 HepG2; Huh-7 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01722 Tiliroside directly binds to TBK1 and inhibits its activity, which inhibits the phosphorylation of Ser349 on p62. Consequently, this decreases the affinity of p62 for Keap1, promotes ubiquitination and degradation of Nrf2 and ferroptosis, and eventually increases the sensitivity of hepatocellular carcinoma cells to sorafenib. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor All animal studies were approved by the Committee on Ethics of Animal Experiments of Binzhou Medical University (approval no: BZMU-IACUC-2021-331, date: 09/10/2021). To generate the ectopic HCC mouse models, HepG2-luciferase cells (HepG2 cells transfected with luciferase gene) were suspended in serum-free media and matrigel (BD Biosciences) at a ratio of 1:1 v/v. A total of 2.5 x 106 HepG2-luciferase cells/100 ul were injected into the left axilla of mice. After reaching a tumor size of 100-150 mm3, all mice were randomly divided into four groups: control (vehicle, intraperitoneal [i.p.]), tiliroside (20 mg/kg,i.p.), sorafenib (30 mg/kg,i.p.), or combination treatment (tiliroside and sorafenib,i.p.). All treatments were administered every 3 d, and the length and width of tumor were measured every 4 d. The formula tumor volume = (length x width2)/2 was used to calculate the tumor volume. Body weight was recorded every 7 d, and the morphology of the tumor was photographed using animal in vivo imaging technology (IVIS Spectrum; PerkinElmer) before the day of sacrifice. The mice were sacrificed 40 d after administration, and the tumors were dissected and weighed. The major organs and xenograft tumors were fixed with 4% paraformaldehyde. REF000942 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00098; CELL00017; CELL00304 HepG2; Hep3B; SMMC-7721; the normal hepatocyte cell line L02 Ferroptosis (hsa04216) Cell ferroptosis
unique01061 Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable. REF000282 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00029; CELL00057; CELL00304; CELL00048; CELL00098; CELL00012 CAF; 293T; 7702; HepG2; Hep3B; Huh-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique01062 The monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of SREBP1 (SREBF1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable. REF000282 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00029; CELL00057; CELL00304; CELL00048; CELL00098; CELL00012 CAF; 293T; 7702; HepG2; Hep3B; Huh-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique01443 SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy. Inducer Up regulation Up regulation Up regulation Driver Driver An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 106 cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. REF000683 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01445 SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy. Inducer Up regulation Up regulation Up regulation Driver Driver An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 106 cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. REF000683 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00646 On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in antiKRAS mutant lung cancer. Inducer Down regulation Up regulation Down regulation Suppressor Driver . REF000876 ICD-11: 2C25 Lung cancer CELL00199; CELL00045; CELL00015; CELL00287 H23; A549; H460; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01429 The natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor A subcutaneous tumor-bearing nude mouse model was established by injecting the flank of BALB/c nude mice with 5 x 106 H460 cells. Ten days later, mice were blindly randomized into four groups and intravenously injected with 200 ul ddH2O containing 0.1% CMC-Na and 1% Tween 80, iron chelators DFO (100 mg/kg/day), curcumenol (200 mg/kg/day), and curcumenol combine DFO. Tumor long diameter, short diameter, and body weight were detected every two days after the first drug treatment. The tumor volume calculation formula: (tumor long diameter x tumor short diameter2)/2. Finally, mice were sacrificed. All tumors were collected for immunohistochemical (IHC) staining. REF000670 ICD-11: 2C25 Lung cancer CELL00056; CELL00015; CELL00057; CELL00246; CELL00076 H1299; H460; HEK293T; CCD19; BEAS-2B Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01430 The natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor A subcutaneous tumor-bearing nude mouse model was established by injecting the flank of BALB/c nude mice with 5 x 106 H460 cells. Ten days later, mice were blindly randomized into four groups and intravenously injected with 200 ul ddH2O containing 0.1% CMC-Na and 1% Tween 80, iron chelators DFO (100 mg/kg/day), curcumenol (200 mg/kg/day), and curcumenol combine DFO. Tumor long diameter, short diameter, and body weight were detected every two days after the first drug treatment. The tumor volume calculation formula: (tumor long diameter x tumor short diameter2)/2. Finally, mice were sacrificed. All tumors were collected for immunohistochemical (IHC) staining. REF000670 ICD-11: 2C25 Lung cancer CELL00056; CELL00015; CELL00057; CELL00246; CELL00076 H1299; H460; HEK293T; CCD19; BEAS-2B Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00648 On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in antiKRAS mutant lung cancer. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000876 ICD-11: 2C25 Lung cancer CELL00199; CELL00045; CELL00015; CELL00287 H23; A549; H460; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01683 In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of non-small cell lung cancer (NSCLC) cells to Cis through the miR-744-5p/miR-615-3p axis. Inducer Up regulation Down regulation Down regulation Driver Suppressor BALB/c nude mice (5 weeks) were provided by Beijing Vital River Laboratory Animal Technology Co., Ltd. (license no: SYXK (Beijing) 20170033). For tumor formation, 8 x 106 A549/Cis cells were subcutaneously injected into the right axilla of each mouse. On the 7th d, Cis (4.0 mg/kg) was intraperitoneally injected into each mouse every 4 days. Then, mice were allocated into 3 groups: Control group (no additional injection); SO group (intraperitoneal injection of soybean oil); and Propofol group [intraperitoneal injection of soybean oil-dissolved propofol (35 mg/kg)]. The volume of the tumor was measured by a caliper every 7 days. Tumor volume was measured according to the formula: V (mm3) = 1/2 ab2 (a: the longest axis of tumor; b: the shortest axis of tumor). Then 35 d after transplantation, mice were euthanatized to measure tumor weight using an electronic balance. A part of transplanted tumors was immediately conserved at liquid nitrogen and -80 . The rest was used for paraffin-embedding and immunohistochemical staining. REF000896 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056 A549; H1299 Ferroptosis (hsa04216) Cell ferroptosis
unique01684 In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of non-small cell lung cancer (NSCLC) cells to Cis through the miR-744-5p/miR-615-3p axis. Inducer Up regulation Down regulation Down regulation Driver Suppressor BALB/c nude mice (5 weeks) were provided by Beijing Vital River Laboratory Animal Technology Co., Ltd. (license no: SYXK (Beijing) 20170033). For tumor formation, 8 x 106 A549/Cis cells were subcutaneously injected into the right axilla of each mouse. On the 7th d, Cis (4.0 mg/kg) was intraperitoneally injected into each mouse every 4 days. Then, mice were allocated into 3 groups: Control group (no additional injection); SO group (intraperitoneal injection of soybean oil); and Propofol group [intraperitoneal injection of soybean oil-dissolved propofol (35 mg/kg)]. The volume of the tumor was measured by a caliper every 7 days. Tumor volume was measured according to the formula: V (mm3) = 1/2 ab2 (a: the longest axis of tumor; b: the shortest axis of tumor). Then 35 d after transplantation, mice were euthanatized to measure tumor weight using an electronic balance. A part of transplanted tumors was immediately conserved at liquid nitrogen and -80 . The rest was used for paraffin-embedding and immunohistochemical staining. REF000896 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056 A549; H1299 Ferroptosis (hsa04216) Cell ferroptosis
unique01800 Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in Non-Small Cell Lung Cancer (NSCLC). Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38 (MAPK14)-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF001030 ICD-11: 2C25.Y Non-small cell lung cancer CELL00056; CELL00045; CELL00203; CELL00375 H1299; A549; H446; H1688 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01801 Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in Non-Small Cell Lung Cancer (NSCLC). Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38 (MAPK14)-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF001030 ICD-11: 2C25.Y Non-small cell lung cancer CELL00056; CELL00045; CELL00203; CELL00375 H1299; A549; H446; H1688 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00301 Zero-valent-iron nanoparticle (ZVI-NP) triggered ferroptosis selectively in lung cancer cells by suppressing NRF2-mediated cytoprotection program, which was attributed to the ZVI-NP-induced disruption of PRKAA1 (AMPK)/mTOR signaling and activation of GSK3/-TrCP-dependent degradation system. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor 5-6-week-old BALB/c nude mice (ZVI@Ag treatment) or NOD/SCID mice (ZVI@CMC treatment) were subcutaneously implanted with 1 x 106 H460 cells. For A549 xenograft model of immunodeficient mouse and spontaneous lung metastasis model, 5-6-week-old NOD/SCID mice were subcutaneously implanted with 5 x 106 A549 cells. For experimental lung metastasis model, H460 cells (1 x 106 cells/200 uL) were resuspended in serum-free medium and injected intravenously (i.v.) into tail-vein of NOD/SCID mice. For subcutaneous model of immunocompetent mouse, LLC cells (5 x 105) were injected into both flank of 6-week-old C57BL/6 mice. REF000424 ICD-11: 2C25 Lung cancer CELL00056; CELL00015; CELL00045; CELL00568; CELL00342; CELL00101 H1299; H460; A549; mouse Lewis lung carcinoma (LLC); MRC-5; IMR-90 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); mTOR signaling pathway (hsa04150) Cell ferroptosis; Cell proliferation
unique01677 RSL3 was able to directly bind to USP11, a recently identified de-ubiquitinase of NRF2, and inactivate USP11 protein to induce NRF2 protein ubiquitination and degradation in KLK lung adenocarcinoma cells. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor After two weeks in house, the mice were subcutaneously injected with A549 cells (100 uL containing 5 x 106 cells/injection) and monitored for tumor cell xenografts to reach approximately 100 mm3. The mice were then divided into two groups (n = 5), the RSL3 treatment (100 mg/kg; dissolved in 5% dimethyl sulfoxide/corn oil; administrated intratumorally twice a day for one week) and control (5% dimethyl sulfoxide/corn oil only) groups. REF000886 ICD-11: 2C25.0 Lung adenocarcinoma CELL00045; CELL00379 A549; H2122 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01812 Isoorientin (IO) can promote ferroptosis and reverse drug resistance in lung cancer through the SIRT6/Nrf2/GPX4 signaling pathway, thus offering a theoretical basis for its potential clinical application. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor The A549/DDP tumor cells were subcutaneously injected (2 x 106 cells/mL) into BALB/c-nu mice under aseptic conditions. 6 days later, the average diameter of the tumor reaches 0.5 cm, and the mice were randomly divided into the 1 mg/kg DDP group and the 1 mg/kg DDP + 25mg/kg IO group. Six mice from each group were intraperitoneally administered medications every 2 days for a total of 10 doses each. REF001044 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01444 SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy. Inducer Up regulation Down regulation Down regulation Driver Suppressor An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 106 cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. REF000683 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01446 SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy. Inducer Up regulation Down regulation Down regulation Driver Suppressor An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 106 cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. REF000683 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00392 RBMS1 ablation inhibited the translation of SLC7A11, reduced SLC7A11-mediated cystine uptake, and promoted ferroptosis. Nortriptyline hydrochloride decreased the level of RBMS1, thereby promoting ferroptosis. Importantly, RBMS1 depletion or inhibition by nortriptyline hydrochloride sensitized radioresistant lung cancer cells to radiotherapy. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Doxorubicin (Dox)- inducible RBMS1 knockdown stable cells (3 x 106 ) were injected subcutaneously into the abdomen side of 6-week-old BALB/c nude mice (Vital River). Mice were fed either with sucrose water or sucrose water containing 0.1% doxycycline hyclate. H1299 vector, 4 H1299 pLKO.1 RBMS1 and H1299 pLKO.1 RBMS1/SLC7A11 cells (2.5 x 106 ) were injected subcutaneously into the abdomen side of 6-week-old BALB/c nude mice(Vital River). The xenograft tumour formation was monitored using callipers every 3 days. REF000528 ICD-11: 2C25 Lung cancer CELL00045; CELL00056; CELL00057 A549; NCI-H1299; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00647 On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in antiKRAS mutant lung cancer. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000876 ICD-11: 2C25 Lung cancer CELL00199; CELL00045; CELL00015; CELL00287 H23; A549; H460; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00514 Nobiletin could induce ferroptosis by regulating the GSK3B-mediated Keap1/Nrf2/HO-1 signalling pathway in human melanoma cells. Hence, nobiletin stands as a promising drug candidate for melanoma treatment with development prospects. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000702 ICD-11: 2C30 Melanoma CELL00609 SK-MEL-28 Pathways in cancer (hsa05200); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00515 Nobiletin could induce ferroptosis by regulating the GSK3B-mediated Keap1/Nrf2/HO-1 signalling pathway in human melanoma cells. Hence, nobiletin stands as a promising drug candidate for melanoma treatment with development prospects. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000702 ICD-11: 2C30 Melanoma CELL00609 SK-MEL-28 Pathways in cancer (hsa05200); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00855 MiR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA) accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137 increased the sensitivity of melanoma cells to erastin- and RSL3-induced ferroptosis. Inducer Down regulation Up regulation Down regulation Suppressor Driver To generate murine subcutaneous tumors, melanoma cells (5 x 106 cells per mouse) were injected subcutaneously into the right posterior flanks of 7-week-old immunodeficient nude mice. When tumors reached a volume of approximately 50 mm3, mice were randomly allocated into groups and treated with erastin for 20 days. The erastin was dissolved in 5% dimethylsulfoxide (DMSO) + corn oil (C8267, Sigma). REF000034 ICD-11: 2C30 Melanoma CELL00069; CELL00163 A375; G-361 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutamate metabolism (hsa00250) Cell ferroptosis; Cell proliferation
unique00128 Gambogenic acid (GNA) significantly inhibited the invasion, migration and EMT in melanoma cells, and these cells exhibited small mitochondrial wrinkling (an important feature of ferroptosis). GNA upregulated the expression of p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the model cells, contributing to the mechanisms underlying GNA-induced ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000187 ICD-11: 2C30 Melanoma CELL00069; CELL00154 A375; A2058 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00501 Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of Cutaneous squamous cell carcinoma cells. And 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. Itraconazole may induce ferroptosis via HMGCS1/ACSL4 axis in A431 cells. Inducer Up regulation Up regulation Up regulation Driver Driver Female BALB/c nude mice (6weeks old and 18-22 g weight) were purchased from the Model Animal Research Center of Nanjing University. A431 cells (5 x 106) in cold DMEM (50 ul) were mixed with Matrigel (50 ul) and injected into mice subcutaneously. After 6 days, the tumor volume was measured and the mice were assigned to three groups. Mice were treated with either normal saline or itraconazole (40 mg/kg oral twice daily; 80 mg/kg oral twice daily). REF000675 ICD-11: 2C31 Cutaneous squamous cell carcinoma CELL00052; CELL00510 A431; Colo16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00890 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00890 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00889 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00889 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00396 The study presented the ferroptosis nanomedicine by loading simvastatin (SIM), a ferroptosis drugs, into zwitterionic polymer coated of magnetic nanoparticles (Fe3O4@PCBMA), thereby improving the therapeutic effect of triple negative breast cancer. SIM could inhibit the expression of HMGCR to downregulate the mevalonate (MVA) pathway and glutathione peroxidase 4 (GPX4), thereby inducing cancer cell ferroptosis. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor MDA-MB-231 cells were injected to subcutaneous of mice to build a tumor model. When the tumor volume reaches about 60 mm3, all mice were randomly divided into five groups (n = 5) for various treatments. Then, mice were treated with PBS, Fe3O4@PCBMA, SIM, Fe3O4-SIM and Fe3O4@PCBMA-SIM through injected intravenously. The injected doses of SIM were 4 mg/kg body weight in each mouse on days 0, 3, 6, and 9. REF000535 ICD-11: 2C60 Triple-negative breast cancer CELL00002; CELL00005 MCF-7; MDA-MB-231 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00441 The treatment of Ketamine induced the levels of MDA, lipid ROS, and Fe2+, while KAT5 or GPX4 overexpression could reverse this effect in breast cancer cells. Ketamine suppresses proliferation and induces ferroptosis and apoptosis of breast cancer cells by targeting KAT5/GPX4 axis. Ketamine may serve as a potential therapeutic strategy for breast cancer. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000587 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00135 MCF-7; T47D Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01076 Metformin promotes ferroptosis of breast cancer by targeting the miR-324-3p/GPX4 axis. The effect of miR-324-3p was mediated by directly targeting glutathione peroxidase 4 (GPX4). Metformin could act as a potential anti-cancer agent through the induction of ferroptosis. Inducer Up regulation Down regulation Down regulation Driver Suppressor Six-week-old athymic nude mice were obtained from Nanjing Biomedical Research Institute of Nanjing University (Nanjing, China). Mice were divided into five groups: sham group, metformin group, metformin + NC group, metformin + miR-324-3p overexpression group, and metformin + miR-324-3p knockdown group (n = 6 in each group). Mice were injected with 3 x 106 MDA-MB-231 cells subcutaneously into the right flank. For the miR-324-3p overexpression or knockdown in the mice, two groups of mice were treated with miR-324-3p overexpression or knockdown lentivirus (GenePharma), respectively, by intratumoral injection of 50 ul of lentivirus (4 x 107 IU/ml) after the tumor cell injection. One day after tumor cell inoculation, the sham-treated group was treated with PBS and metformin-treated groups were treated with 200 mg/kg metformin every 2 days through intraperitoneal injection. REF000310 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00002 MDA-MB-231; MCF-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique00888 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00888 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00887 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00887 Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 107 cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. REF000062 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00010; CELL00056; CELL00045; CELL00141 MDA-MB-231; Hs578T; H1299; A549; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation; Cell migration; Cell invasion
unique00296 Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 106 cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day. REF000417 ICD-11: 2C60 Triple-negative breast cancer CELL00005; CELL00010; CELL00002; CELL00135; CELL00277; CELL00156; CELL00111 MDA-MB-231; HS578T; MCF-7; T47D; HBL-100; BT549; MDA-MB-453; NHFB Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00306 The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. Inducer Up regulation Down regulation Down regulation Driver Suppressor SPF-level male nude mice aged 56weeks and weighted around 20 g were purchased from Vitalriver (China). All mice were maintained in a 12-hour circadian rhythm, and had free access to water and food. Cancer cells were subcutaneously injected into the right flank of mice. Lidocaine was administrated to mice at a dose of 1.5 mg per kg injected through the vail tails. For control group, the mice were treated with saline. Tumor volume and mice body weight were monitored every 5 days. REF000432 ICD-11: 2C60-2C65 Breast cancer CELL00128; CELL00135 SKOV-3; T47D Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique00309 Metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc-inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor T47D xenografts were established in 5-week-old nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 107 cells mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, Metformin, SAS, and Metformin + SAS groups). Metformin (200 mg/kg/day) was provided in drinking water. Sulfasalazine was dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 250 mg/kg once a day. REF000438 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00135; CELL00086; CELL00075; CELL00277; CELL00005; CELL00156 MCF-7; T47D; HCC1937; Bcap37; NHFB; HBL-100; MDAMB231; BT549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00253 Robustaflavone A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways. Inducer Down regulation Up regulation Down regulation Suppressor Driver . REF000336 ICD-11: 2C60-2C65 Breast cancer CELL00002 MCF-7 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00305 The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. Inducer Up regulation Down regulation Down regulation Driver Suppressor SPF-level male nude mice aged 56weeks and weighted around 20 g were purchased from Vitalriver (China). All mice were maintained in a 12-hour circadian rhythm, and had free access to water and food. Cancer cells were subcutaneously injected into the right flank of mice. Lidocaine was administrated to mice at a dose of 1.5 mg per kg injected through the vail tails. For control group, the mice were treated with saline. Tumor volume and mice body weight were monitored every 5 days. REF000432 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00135 SKOV-3; T47D Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01814 NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 and activate the AMPK signaling pathway, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days. REF001046 ICD-11: 2C73 Ovarian cancer CELL00532; CELL00341 Anglne; HO8910PM Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique01815 NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 and activate the AMPK signaling pathway, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days. REF001046 ICD-11: 2C73 Ovarian cancer CELL00532; CELL00341 Anglne; HO8910PM Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique00053 There is a significant correlation between the expression of ANGPTL4 and TAZ (encoded by WWTR1) in the TCGA ovarian tumor dataset. Carboplatin-treated CAOV2R cells are less sensitive to ferroptosis and have a lower level of TAZ (TAFAZZIN). TAZ promotes ferroptosis in ovarian cancers by regulating ANGPTL4 and NOX2, offering a novel therapeutic potential for ovarian tumors with TAZ activation. Suppressor Down regulation Down regulation Up regulation Driver Driver . REF000102 ICD-11: 2C73 Ovarian cancer CELL00478; CELL00265 CAOV2; TOV-21G Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis
unique00634 Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000869 ICD-11: 2C76 Corpus uteri cancer CELL00024 EC cells (Ishikawa) MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00633 Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000869 ICD-11: 2C76 Corpus uteri cancer CELL00024 EC cells (Ishikawa) MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00635 Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells. Inducer Down regulation Up regulation Down regulation Suppressor Marker/Suppressor/Driver . REF000869 ICD-11: 2C76 Corpus uteri cancer CELL00024 EC cells (Ishikawa) MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00823 Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 ( HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. REF000005 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00055; CELL00108 HeLa; U2OS; LNCaP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00823 Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection. REF000005 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00055; CELL00108 HeLa; U2OS; LNCaP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00184 Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs( AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000245 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00216 HeLa; SAS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00185 Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000245 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00216 HeLa; SAS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00186 Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5, AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000245 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00216 HeLa; SAS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00186 Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000245 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00216 HeLa; SAS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00185 Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000245 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00216 HeLa; SAS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00184 Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000245 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00216 HeLa; SAS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00492 Curcumin induces ferroptosis in tumor cells by upregulating the expression of ADAMTS18, thereby enhancing the sensitivity of clear cell renal cell carcinoma (ccRCC) to sunitinib. And Curcumin can significantly inhibit FTH1 and FTL1 gene expression in tumor tissues of nude mice. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000658 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00153; CELL00021 A498; 786-O Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01532 Icariside II (ICS II) treatment triggered ferroptosis in renal cell carcinoma (RCC) cells by downregulating GPX4 in a p53-independent manner. Furthermore, ICS II treatment resulted in upregulation of miR-324-3p, which negatively regulated the expression of GPX4. Inducer Up regulation Down regulation Down regulation Driver Suppressor A total of 30 male BALB/c nude mice (4-6 weeks old; 18-23 g) were randomized into four groups (7-8 mice per group): i) control group; ii) treated with 15 mg/kg ICS II; iii) treated with 25 mg/kg ICS II; and, iv) treated with 35 mg/kg ICS II. ACHN and Caki-1 cells (1 x 107) were suspended in 50 ul MEM media mixed with 50 ul Matrigel (BD Biosciences) and injected subcutaneously into the right flank of mice with 1.5%pentobarbital sodium (60 mg/kg body weight; intraperitoneal injection) under anesthesia. Weight lossof more than 20% was considered a humane endpoint. REF000749 ICD-11: 2C90 Renal cell carcinoma CELL00155; CELL00153; CELL00021; CELL00081; CELL00057 ACHN; A498; 786-O; Caki-1; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01751 GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients. . . . Up regulation Suppressor Marker/Suppressor All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed. REF000972 ICD-11: 2F37.Y Preeclampsia CELL00599; CELL00057 MMQ; HEK-293T Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01750 GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients. . . . Up regulation Suppressor Suppressor All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed. REF000972 ICD-11: 2F37.Y Preeclampsia CELL00599; CELL00057 MMQ; HEK-293T Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01749 GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients. . . . Up regulation Suppressor Marker/Suppressor All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed. REF000972 ICD-11: 2F37.Y Preeclampsia CELL00599; CELL00057 MMQ; HEK-293T Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01752 GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients. . . . Down regulation Driver Suppressor All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed. REF000972 ICD-11: 2F37.Y Preeclampsia CELL00599; CELL00057 MMQ; HEK-293T Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01748 GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and FTH1, and circOMA1 attenuated cabergoline (CAB)-induced ferroptosis in MMQ cells in vivo and in vitro. circOMA1 may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients. . . . Up regulation Suppressor Suppressor All animal studies were performed in the Laboratory Animal Center of Sun Yat-sen University and conducted in accordance with the institutional policies for animal care. Approximately 5 x 106 MMQ_vector cells or MMQ_circOMA1 cells in 150 uL were injected into the right flank of BALB/c nude mice (total of 12 female mice, 4-6 weeks, SCXK2021-0029). After tumor formation (10 days), mice were randomly divided into four groups (n = 3 mice/group) as follows: vector (saline solution, intraperitoneally injected), circOMA1 (saline solution, intraperitoneally injected), vector + CAB (0.5 mg/kg, intraperitoneally injected), and circOMA1 + CAB (0.5 mg/kg, intraperitoneally injected) in accordance with previous studies. CAB was injected intraperitoneally every 2 days for 14 days. The size of the tumor was measured every 3 days. On Day 15, mice were anesthetized with 0.3% pentobarbital sodium solution and then sacrificed by cervical dislocation, and the xenograft tumors were removed and weighed. REF000972 ICD-11: 2F37.Y Preeclampsia CELL00599; CELL00057 MMQ; HEK-293T Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00287 Sodium hydrosulfide (NaHS) ameliorated the ferroptosis via increasing the protein expressions of SLC7A11, glutathione peroxidase 4 (GPX4), and cystathionine -synthase (CBS), reducing the pro-inflammatory cytokines, decreasing the levels of Fe2+, MDA, ROS, and lipid ROS. In conclusion, NaHS did alleviate anxiety and depression. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Adult male 22-24 g C57BL/6J mice were purchased from the Vital River Laboratory Animal Technology Co., Ltd. Mice were randomly divided into four groups, the control group (CON group, n = 8), diabetes mellitus group (DM group, n = 8), DM + sodium hydrosulfide (DM + 5.6 mg/kg NaHS, n = 8) group, and CON + sodium hydrosulfide (CON + 5.6 mg/kg NaHS, n = 8) group. In this experiment, mice have received daily intraperitoneally injection of NaHS during the last 4 weeks. Then, all mice were tested by the open field test (OFT), elevated plus maze test (EPM test), forced swimming test (FST), and tail suspension test (TST). REF000401 ICD-11: 6A70 Depression CELL00544 BV2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01149 The activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs. Inducer Up regulation Down regulation Down regulation Driver Suppressor The specific-pathogen free (SPF) male C57BL/6 mice (8-week-old, SCXK (Beijing) 2016-0006) were purchased from Beijing Vital River Laboratory Animal Technology Limited Company. A total of 48 mice were randomly assigned to 4 groups (n = 12): a control group (no stress + physiological saline), a CUMS group (CUMS + physiological saline), a Xiaoyaosan group (CUMS + Xiaoyaosan treatment) and a fluoxetine group (CUMS + fluoxetine treatment). REF000382 ICD-11: 6A70 Depression CELL10127 Hippocampal tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00496 The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Male C57BL/6J mice (aged 7-8 weeks) and retired male CD-1 mice (aged 16-20 weeks) were obtained from the Experimental Animal Centre of Chongqing Medical University (Chongqing, China). The experimental animals were housed in cages under a 12 h light/12 h dark cycle (lights on at 8:00 a.m.), 60 ± 5% humidity, and a temperature of 23 ± 1 with access to water and food freely. All experimental procedures were conducted in accordance with the Ethics Committee of Chongqing Medical University. EDA was purchased from Sigma-Aldrich (St. Louis, USA) and was dissolved in Vehicle (NaCl, 0.9%) at a dosage of 10 mg/kg. EX527 (a Sirt1 inhibitor) and ML385 (a Nrf2 inhibitor) were obtained from MedChemExpress (New Jersey, USA). REF000661 ICD-11: 6A70 Depression CELL10005 Brain tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00626 Gastrodin (GAS) inhibited ferroptosis in hippocampal neurons by activating the Nrf2/ Keap1-GPx4 signaling pathway, suggesting its possible application as a functional food for improving vascular dementia by inhibiting ferroptosis. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor Male Sprague-Dawley rats (weight 260 ± 20 g; Guizhou Medical University Experimental Animal Center; Certificate No. SCXK2018-0001; Grant No. 2200483) were reared in a specific pathogen-free environment with 12 h light/dark cycle and 55% ± 10% humidity at a temperature of 20~25 , were provided with sufficient feed and sterile drinking water and fasted for 6 h before and after surgery. All animal experiments were performed in accordance with the Declaration of Helsinki and the Guide for the Care and Use of Laboratory Animals. REF000860 ICD-11: 6D81 Vascular dementia CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique01094 1-methyl-4-phenylpyridinium (Cyperquat) decreased cell viability, GPX4, and Trx-1 (TXN). The decreased GPX4 and GSH, and increased ROS were inhibited by Fer-1 and Trx-1 overexpression. Trx-1 reversed the decreases of GPX4 and tyrosine hydroxylase (TH) induced by MPTP in the substantia nigra pars compacta (SNpc). Trx-1 inhibits ferroptosis in parkinson's disease through regulating GPX4 and GSH. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor Male C57BL/6 mice wild-type (WT), 8 weeks of age, were from Chongqing Medical University, China. Mice were divided into four groups (n = 10-13 per group), control group, MPTP group, h-Trx-1 Tg group, and h-Trx-1 Tg + MPTP group. Control and h-Trx-1 Tg groups were administered saline only. For the Trx-1 knockdown experiment, mice were divided into six groups (n = 10-13 per group), control + saline group, control + MPTP group, AAV9-vehicle + saline group, AAV9-vehicle + MPTP group, AAV9-shRNA-mTrx-1 + saline group, and AAV9-shRNA-mTrx-1 + MPTP. REF000335 ICD-11: 8A00 Parkinson disease CELL00597; CELL00042 PC12; SH-SY5Y Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00207 a-Lipoic acid (a-LA) suppressed cell viability decline and mitigated ferroptosis in an MPP-induced PC12 cell model of parkinson's disease (PD) via activating the PI3K/Akt/Nrf2 pathway. These results discovered a novel a-LA-based therapy for PD patients, and activating the PI3K/Akt/Nrf2 pathway might be developed as a promising therapeutic approach for PD. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor . REF000271 ICD-11: 8A00 Parkinson disease CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique00671 L. lactis MG1363-pMG36e-GLP-1 exerts neurotrophic effects via activating the Keap1/Nrf2/GPX4 signalling pathway to down-regulate ACSL4 and up-regulate FSP1 to suppress ferroptosis. These results indicated that the neurotrophic effects of the next-generation probiotics L. lactis MG1363-pMG36e-GLP-1 against MPTP-induced Parkinsonism are mediated by modulating oxidative stress, inhibiting ferroptosis, and redressing dysbiosis. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor Fifty male C57BL/6 mice provided by Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China) resided in an animal house (temperature 26 ± 1 , humidity 50 ± 10%), in which the light was on for 12 h and off for 12 h. Mice were acclimatised for 1 week and allowed water and animal food with no limitations. Then, all mice were stochastically divided into 5 groups using random number tables available online (https://www.random-online.com/, accessed on 26 December 2021), including: (1) C group, a control group treated with normal saline for 7 consecutive days (n = 10); (2) M group, a model group with intraperitoneal injection of 20 mg/kg/day MPTP (Sigma-Aldrich, Taufkirchen, Germany, M0896) for 7 consecutive days (n = 10); (3) L group, treated with MPTP and 0.4 mg/kg/day liraglutide for 7 consecutive days (n = 10); (4) R group, treated with MPTP and 109 colony-forming unit (CFU) L. lactis MG1363 for 7 consecutive days via gavage (n = 10); (5) RG group, treated with MPTP and 109 CFUL. lactis MG1363-pMG36e-GLP-1 for 7 consecutive days via gavage (n = 10). All animals survived treatment and all animal experiments were administered from 9:00 to 12:00 in the morning to reduce systematic errors. REF000897 ICD-11: 8A00 Parkinson disease CELL10116; CELL10005 Colon tissues; brain tissues Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique00265 As a classic drug employed inin vitromodels of Parkinson's disease, 1-methyl-4-phenylpyridinium (MPP) can induce senescence in PC12 cells. The expression of the ferroptosis-related proteins ASCL4 was upregulated and FTH1 was downregulated, which promoted accumulation of lipid peroxides and eventually led to ferroptosis. By rescuing MPP-induced ferroptosis, cell senescence could be inhibited, and its molecular mechanism was related to a p53/SLC7A11/GPX4 signaling pathway. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000362 ICD-11: 8A00 Parkinson disease CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00576 D-penicillamine can be repurposed to cure seizure disorders such as epilepsy. D-penicillamine reveals the amelioration of seizure-induced neuronal injury via inhibiting Aqp11-dependent ferroptosis. Furthermore, ferroptosis-associated indices including acyl-coA synthetase long chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (Ptgs2) gene and lipid peroxide (LPO) level were significantly decreased in KA mouse model after DPA treatment. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were provided by at the Centre for Animals of Central South University (Changsha, China). To prepare the seizure mouse model, the mice underwent the intrahippocampal injection of KA as described in our previous investigation. For short, mice were anesthetized with sodium phenobarbital (50 mg/kg, i.p.) and carefully placed on a stereotaxic apparatus. Then, KA (1 uL, 250 ng/uL dissolved in saline) was stereotactically injected into the hippocampus according to the following coordinates: anteroposterior -2.0 mm; lateral -1.3 mm; dorsoventral -1.2 mm. After injection, the infusion needle was kept in place for 5-10 min to avoid liquid reflux. Mice in the control group underwent the same surgical procedure but received injection with an equal volume of phosphate buffered saline (PBS) instead of KA. REF000807 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00596 Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. REF000825 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00599 The association between the Nrf2-mediated ferroptosis pathway and seizures in a clinical setting. Quercetin effectively protects against seizure-induced neuron death in vivo and in vitro and alleviates cognitive function impairment via the SIRT1/Nrf2/SLC7A11/GPX4 pathway. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were obtained from Gempharmatech Co., Ltd (Changzhou, China). All mice were housed in cages with standard laboratory conditions: a consistent temperature of 24 , a 12 h light/dark cycle, and free access to water and food. The mice were randomized into four groups: 1) the KA group (n = 6), injected intraperitoneally with 20 mg/kg KA, as described in a previous study; while 2) the control group (n = 6), injected intraperitoneally with an equal volume of PBS; 3) the KA + QCT group (n = 6): this group was givenintragastric administrationof 50 mg/kg of QCT once daily for 21 days before KA injection based on the literature; and 4) the KA+ferrostatin1 (Fer-1) group (n = 6), injected intraperitoneally with a well-known ferroptosis inhibitor (3 mg/kg Fer-1) for 21 days before KA administration, as described in a previous study. REF000826 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
dupunique00112 Apigenin can efficiently reduce the expression of intracellular MPO and increase the levels of GPX4 and SIRT1, thereby conferring neuroprotection through regulation of kainic acid (KA)-induced ferroptosis. And the level of Ac-p53 inside the brains treated with apigenin was down-regulated, suggesting that the p53-mediated ferroptosis pathway might be blocked. Overall, apigenin was screened and confirmed as an efficient lead compound for epilepsy prevention and treatment. Suppressor Down regulation Up regulation Down regulation Driver Suppressor 5-weeks-old kainate (KA)-induced BALB/c nude mice, a widely used epilepsy mouse model, were performed with intraperitoneal (i.p.) injection of KA (6 mg/kg). Pre-treatment 21 with antioxidant apigenin (60 mg/Kg, 2 days) or post-treatment with apigenin (60 mg/Kg, 1 day), mice were injected with KA (6 mg/kg) via intraperitoneal (i.p.) injection, and then HCP (0.5 mg/Kg) were injected by intravenous (i.v.) injection. In vivo and Ex vivo fluorescence images of relative ClO levels in mice brains 5, 15, 30, 45, and 60 min post injection of HCP were further performed by using the IVIS Spectrum imaging system (Nanjing University) with an excitation filter of 430 nm and the collection wavelength range is from 500-600 nm. REF000165 ICD-11: 8A66 Epilepsy CELL00042 SH-SY5Y Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00597 The association between the Nrf2-mediated ferroptosis pathway and seizures in a clinical setting. Quercetin effectively protects against seizure-induced neuron death in vivo and in vitro and alleviates cognitive function impairment via the SIRT1/Nrf2/SLC7A11/GPX4 pathway. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were obtained from Gempharmatech Co., Ltd (Changzhou, China). All mice were housed in cages with standard laboratory conditions: a consistent temperature of 24 , a 12 h light/dark cycle, and free access to water and food. The mice were randomized into four groups: 1) the KA group (n = 6), injected intraperitoneally with 20 mg/kg KA, as described in a previous study; while 2) the control group (n = 6), injected intraperitoneally with an equal volume of PBS; 3) the KA + QCT group (n = 6): this group was givenintragastric administrationof 50 mg/kg of QCT once daily for 21 days before KA injection based on the literature; and 4) the KA+ferrostatin1 (Fer-1) group (n = 6), injected intraperitoneally with a well-known ferroptosis inhibitor (3 mg/kg Fer-1) for 21 days before KA administration, as described in a previous study. REF000826 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00577 D-penicillamine (DPA) can be repurposed to cure seizure disorders such as epilepsy. Furthermore, ferroptosis-associated indices including acyl-coA synthetase long chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (Ptgs2) gene and lipid peroxide (LPO) level were significantly decreased in KA mouse model after DPA treatment. The effects of DPA on ferroptosis process are dependent upon Aqp11. Suppressor Up regulation Down regulation Down regulation Suppressor Marker Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were provided by at the Centre for Animals of Central South University (Changsha, China). To prepare the seizure mouse model, the mice underwent the intrahippocampal injection of KA as described in our previous investigation. For short, mice were anesthetized with sodium phenobarbital (50 mg/kg, i.p.) and carefully placed on a stereotaxic apparatus. Then, KA (1 uL, 250 ng/uL dissolved in saline) was stereotactically injected into the hippocampus according to the following coordinates: anteroposterior -2.0 mm; lateral -1.3 mm; dorsoventral -1.2 mm. After injection, the infusion needle was kept in place for 5-10 min to avoid liquid reflux. Mice in the control group underwent the same surgical procedure but received injection with an equal volume of phosphate buffered saline (PBS) instead of KA. REF000807 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00595 Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. REF000825 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00598 The association between the Nrf2-mediated ferroptosis pathway and seizures in a clinical setting. Quercetin effectively protects against seizure-induced neuron death in vivo and in vitro and alleviates cognitive function impairment via the SIRT1/Nrf2/SLC7A11/GPX4 pathway. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were obtained from Gempharmatech Co., Ltd (Changzhou, China). All mice were housed in cages with standard laboratory conditions: a consistent temperature of 24 , a 12 h light/dark cycle, and free access to water and food. The mice were randomized into four groups: 1) the KA group (n = 6), injected intraperitoneally with 20 mg/kg KA, as described in a previous study; while 2) the control group (n = 6), injected intraperitoneally with an equal volume of PBS; 3) the KA + QCT group (n = 6): this group was givenintragastric administrationof 50 mg/kg of QCT once daily for 21 days before KA injection based on the literature; and 4) the KA+ferrostatin1 (Fer-1) group (n = 6), injected intraperitoneally with a well-known ferroptosis inhibitor (3 mg/kg Fer-1) for 21 days before KA administration, as described in a previous study. REF000826 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
dupunique00594 Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures in Epilepsy. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. REF000825 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01156 Paeonol (PAN) inhibits the progression of intracerebral haemorrhage via the HOTAIR/UPF1/ACSL4 signalling pathway. Thus, PAN could act as a new agent for the treatment of ferroptosis in intracerebral haemorrhage. Suppressor Down regulation Down regulation Up regulation Driver Driver C57BL/6 mice (aged 8-10 weeks, Vital River, Beijing, China) were housed in SPF conditions. The animal study was performed according to the National Institutes of Health Guide and approved by the Ethics Committees of Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan University. REF000393 ICD-11: 8B00 Intracerebral haemorrhage CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique01157 Paeonol (PAN) inhibits the progression of intracerebral haemorrhage via the HOTAIR/ UPF1/ACSL4 signalling pathway. Thus, PAN could act as a new agent for the treatment of ferroptosis in intracerebral haemorrhage. Suppressor Up regulation Down regulation Down regulation Suppressor Driver C57BL/6 mice (aged 8-10 weeks, Vital River, Beijing, China) were housed in SPF conditions. The animal study was performed according to the National Institutes of Health Guide and approved by the Ethics Committees of Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan University. REF000393 ICD-11: 8B00 Intracerebral haemorrhage CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00742 Artesunate alleviates intracerebral haemorrhage secondary injury by inducing ferroptosis in M1-polarized microglia and suppressing inflammation through AMPK/mTORC1/GPX4 pathway Inducer Inhibit function Down regulation Down regulation Driver Suppressor Rats were anaesthetised through intraperitoneal injection of pentobarbital (40 mg/kg) and placed onto a stereotaxic instrument (RWD Life Science Co., Ltd.). A 1-cm midline incision was performed in the rat scalp to expose the intersection point. Then, a hole 3.2 mm lateral and 1.4 mm anterior to the right bregma was produced. Next, 1.0 ul collagenase type IV (0.25 IU/ul; C5138; Sigma-Aldrich, USA) was injected into the basal ganglia via a microinjection pump (4.2 mm depth below the endocranium) at a rate of 0.2 ul/min. The needle was maintained for 5 min after injection to prevent backflow. Thereafter, the skin incision was closed using sutures. Rats in the sham group received 1.0 ul saline instead of collagenase type IV. REF000967 ICD-11: 8B00 Intracerebral haemorrhage CELL00544 BV2 mTOR signaling pathway (hsa04150); Ferroptosis (hsa04216) Cell ferroptosis
unique01518 Pioglitazone (PDZ), a PPAR agonist, promotes Gpx4 expression through the interaction between PPAR and the Nrf2 pathway, inhibits ferroptosis of neurons after intracerebral hemorrhage (ICH), and promotes the recovery of neural function. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor The rats underwent surgery using an ultraclean table and were fixed in a stereotaxic frame. The scalp was opened to expose the anterior brain region. A dental drill was used to drill a 1-mm-diameter hole in the skull surface. Blood (100 ul) was collected from the rat tail vein and injected into the rat striatum with a microsyringe (stereotaxic coordinates; 2 mm lateral to the midline, 0.2 mm posterior to bregma, and 5.5 mm deep below the skull). First, 60 ul of autogenous blood were injected at a rate of 2 ul/min, and the next 40 ul of blood were injected at 5 ul/min. Finally, the needle was left for 10 min before being removed. REF000735 ICD-11: 8B00 Intracerebral haemorrhage CELL10180; CELL10005 Primary nerve cell; Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01519 Pioglitazone (PDZ), a PPAR agonist, promotes Gpx4 expression through the interaction between PPAR and the Nrf2 pathway, inhibits ferroptosis of neurons after intracerebral hemorrhage (ICH), and promotes the recovery of neural function. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor The rats underwent surgery using an ultraclean table and were fixed in a stereotaxic frame. The scalp was opened to expose the anterior brain region. A dental drill was used to drill a 1-mm-diameter hole in the skull surface. Blood (100 ul) was collected from the rat tail vein and injected into the rat striatum with a microsyringe (stereotaxic coordinates; 2 mm lateral to the midline, 0.2 mm posterior to bregma, and 5.5 mm deep below the skull). First, 60 ul of autogenous blood were injected at a rate of 2 ul/min, and the next 40 ul of blood were injected at 5 ul/min. Finally, the needle was left for 10 min before being removed. REF000735 ICD-11: 8B00 Intracerebral haemorrhage CELL10180; CELL10005 Primary nerve cell; Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01793 Dihydromyricetin (DMY) may attenuate symptoms of intracerebral hemorrhage (ICH) in mice, and its potential mechanisms are closely linked to LCN2/system Xc-. The ICH-induced augmentation of LCN2 expression leads to the formation of LCN2-SLC3A2 complexes, which suppress the transport activity of system Xc- and result in the accumulation of ROS and the emergence of ferroptosis. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Male C57BL/6 mice, aged 8-10 weeks and weighing 22-25 g, were purchased from the Hubei Provincial Center for Disease Control and Prevention in Wuhan, China. Mice were initially administered with 1% sodium pentobarbital (70 mg/kg; Sinopharm Chemical Agent Co., Ltd., Shanghai, China) intraperitoneally. Subsequently, they were secured on a stereotaxic device (RWD Life Science Co., Shenzhen). 0.6 ul of collagenase (1 ku/ml) was injected into the caudate nucleus of the mice (bregma 0: 0.5 mm anterior, 2 mm left lateral and 3.5 mm deep) with the help of a brain stereotactic sampling needle (Hamilton). REF001017 ICD-11: 8B00 Intracerebral haemorrhage CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
dupunique00285 Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection). REF000400 ICD-11: 8B00 Intracerebral haemorrhage CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); p53 signaling pathway (hsa04115) Cell ferroptosis; Cell proliferation
unique00285 Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection). REF000400 ICD-11: 8B00 Intracerebral haemorrhage CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); p53 signaling pathway (hsa04115) Cell ferroptosis; Cell proliferation
unique00588 Astragaloside IV (AS-IV) triggered Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of subarachnoid hemorrhage (SAH). The Nrf2 inhibitor ML385 blocked the beneficial effects of neuroprotection. Ferroptosis is profoundly implicated in facilitating EBI in SAH, and that AS-IV thwarts the process of ferroptosis in SAH by activating Nrf2/HO-1 pathway. The liberation of Nrf2 from Keap1, its cytoplasmic repressor will provoke Nrf2 accumulation in the nucleus. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor SAH model was constructed by applying endovascular perforation in the rats, according to the protocol introduced in a previous study (Wei et al., 2020), except for slight modifications. Briefly, after performing intraperitoneal anesthesia with 40 mg/kg sodium pentobarbital, the right common carotid, external and internal carotid arteries of the rats were exposed and isolated. The right external carotid artery was ligated, and a 4-0 single-strand nylon thread was used to insert the right internal carotid artery through the stump of the external carotid artery and the bifurcation of the common carotid artery. When resistance is felt when the suture enters the intracranial segment, proceed approximately 3 mm to penetrate internal carotid artery at the bifurcation of middle cerebral artery. The suture was held in this position for 10 s and was then withdrawn. The rats in the Sham group went through an identical procedure, without the suture at the point of resistance. Throughout the experiment, the body temperature of the rats was sustained at around 37 by using a thermal blanket. After the wounds were sutured, the rats were placed in a separate cage and neurological function was closely observed. REF000816 ICD-11: 8B01 Subarachnoid hemorrhage CELL10005 Brain tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00745 Sevoflurane treatment inhibits ferroptosis and increases apoptosis events by inhibiting the SP1/ASCL4 axis, thereby reducing cerebral ischemia-reperfusion injury damage. Suppressor Down regulation Down regulation Up regulation Driver Driver Adult male SD rats (250-300 g) were purchased from Charies River (Beijing, China). The animals were placed in laboratory cages, kept on a 12-h light-dark cycle, and had free access to food and water throughout the study. The rats were randomly assigned to the sham (only the left neck was exposed without ligation) group, MACO group, and sevo + MACO (2.5% sevoflurane before refusion) group. The MCAO model was made by a modified nylon suture method. After 1 h of ischemia, the suture was gently pulled to the beginning of the external carotid artery and re-perfused for 24 h. For sevoflurane postconditioning, rats were stabilized in a gas-tight anesthesia chamber with sevoflurane inhalation for 1 h at the onset of blood refusion. Sevoflurane (AbbVie, Japan) was delivered at a concentration of 2.5% through a vaporizer (Vapor 2000, Germany). In the sham or MCAO group, rats were only exposed to the mixed gas (95% O2 and 5% CO2). REF000970 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00609 Dihydromyricetin (DHM) repressed ferroptosis by inhibiting the SPHK1/mTOR signaling pathway, thereby alleviating cerebral ischemia reperfusion injury. Moreover, the expression levels of glutathione peroxidase 4 (GPX4) was enhanced while the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4) and phosphatidylethanolamine binding protein 1 (PEBP1) were reduced in OGD/R-treated HT22 cells in the presence of DHM. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Rats were anesthetized by pentobarbital sodium at a dosage of 40 mg/kg by intraperitoneal injection. Rats were first anchored on to an operating table in the supine position. The fur around the incision was shaved and then disinfected. Subsequently, the neck of each rat was incised in the middle to expose the right common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA). The proximal end of the CCA and ECA were ligated and severed using a 0.285 mm nylon suture. The suture was inserted from the ECA stump through the ICA to reach the MCA. The MCA was then occluded for 2 h to create ischemic conditions. Next, the nylon suture was slowly pulled out to restore blood flow and simulate reperfusion condition. REF000834 ICD-11: 8B10 Cerebral ischemia CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00608 Dihydromyricetin (DHM) repressed ferroptosis by inhibiting the SPHK1/ mTOR signaling pathway, thereby alleviating cerebral ischemia reperfusion injury. Moreover, the expression levels of glutathione peroxidase 4 (GPX4) was enhanced while the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4) and phosphatidylethanolamine binding protein 1 (PEBP1) were reduced in OGD/R-treated HT22 cells in the presence of DHM. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Rats were anesthetized by pentobarbital sodium at a dosage of 40 mg/kg by intraperitoneal injection. Rats were first anchored on to an operating table in the supine position. The fur around the incision was shaved and then disinfected. Subsequently, the neck of each rat was incised in the middle to expose the right common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA). The proximal end of the CCA and ECA were ligated and severed using a 0.285 mm nylon suture. The suture was inserted from the ECA stump through the ICA to reach the MCA. The MCA was then occluded for 2 h to create ischemic conditions. Next, the nylon suture was slowly pulled out to restore blood flow and simulate reperfusion condition. REF000834 ICD-11: 8B10 Cerebral ischemia CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00522 L-F001 could restore GPX4 and glutamate-cysteine ligase modifier subunit (GCLM) levels, and significantly deceased Cyclooxygenase (COX-2) levels to rescue the lipid peroxidation imbalance. And L-F001 could reduce RSL3-induced c-Jun N-terminal kinase (JNK) activation, which might be a potential drug target for for the therapy of ferroptosis-related diseases, such as cerebral ischemia. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF000720 ICD-11: 8B10 Cerebral ischemia CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00739 Astragaloside IV (AST IV) increased the P62 (SQSTM1) and Nrf2 levels and decreased the Keap1 levels. P62 silencing reduced the effects of AST IV on the P62/Keap1/Nrf2 pathway and ferroptosis. Our findings suggest that AST IV mitigates cerebral ischemia-reperfusion injury by inhibiting ferroptosis via activation of the P62/Keap1/Nrf2 pathway. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Rats were randomly divided into the Sham, middle cerebral artery occlusion-reperfusion (MCAO/R), and MCAO/R + AST IV (28 mg/kg) groups. The MCAO/R + AST IV group was intragastrically injected with 10 mL/kg AST IV at 50, 26, and 2 h before modelling (Xiao et al., 2021). The Sham and MCAO/R groups received equal amounts of normal saline. As described previously, the modified Longa method (Longa et al., 1989) was used to establish the MCAO/R model. After anaesthesia with 2%sodium pentobarbital, the left common carotid artery(CCA), the external carotid artery(ECA), and the internal carotid artery(ICA) were isolated. The distal end of the ECA was ligated, a small incision was made at the stump of the ECA, and a suture (Batch number: 2636A2, Beijing Seinong Technology Co., Ltd., Beijing, China; head-end diameter: 0.36 ± 0.02 mm) was inserted into the ICA from the ECA through the bifurcation of the CCA. To achieve cerebral ischaemia, the head-end was used to block blood flow in the middle cerebral artery until the intracranial segment of the ICA was inserted. The suture was removed after 2 h, and follow-up experiments were performed 24 h after reperfusion. In the Sham group, the CCA, ECA, and ICA were exposed and separated, but no sutures were inserted. Penicillin powder was used to fight infection after operation. REF000962 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00042 SH-SY5Y Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00740 Astragaloside IV (AST IV) increased the P62 (SQSTM1) and Nrf2 levels and decreased the Keap1 levels. P62 silencing reduced the effects of AST IV on the P62/ Keap1/Nrf2 pathway and ferroptosis. Our findings suggest that AST IV mitigates cerebral ischemia-reperfusion injury by inhibiting ferroptosis via activation of the P62/ Keap1/Nrf2 pathway. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor Rats were randomly divided into the Sham, middle cerebral artery occlusion-reperfusion (MCAO/R), and MCAO/R + AST IV (28 mg/kg) groups. The MCAO/R + AST IV group was intragastrically injected with 10 mL/kg AST IV at 50, 26, and 2 h before modelling (Xiao et al., 2021). The Sham and MCAO/R groups received equal amounts of normal saline. As described previously, the modified Longa method (Longa et al., 1989) was used to establish the MCAO/R model. After anaesthesia with 2%sodium pentobarbital, the left common carotid artery(CCA), the external carotid artery(ECA), and the internal carotid artery(ICA) were isolated. The distal end of the ECA was ligated, a small incision was made at the stump of the ECA, and a suture (Batch number: 2636A2, Beijing Seinong Technology Co., Ltd., Beijing, China; head-end diameter: 0.36 ± 0.02 mm) was inserted into the ICA from the ECA through the bifurcation of the CCA. To achieve cerebral ischaemia, the head-end was used to block blood flow in the middle cerebral artery until the intracranial segment of the ICA was inserted. The suture was removed after 2 h, and follow-up experiments were performed 24 h after reperfusion. In the Sham group, the CCA, ECA, and ICA were exposed and separated, but no sutures were inserted. Penicillin powder was used to fight infection after operation. REF000962 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00042 SH-SY5Y Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00524 L-F001 could restore GPX4 and glutamate-cysteine ligase modifier subunit (GCLM) levels, and significantly deceased Cyclooxygenase (COX-2) levels to rescue the lipid peroxidation imbalance. And L-F001 could reduce RSL3-induced c-Jun N-terminal kinase (JNK) activation, which might be a potential drug target for for the therapy of ferroptosis-related diseases, such as cerebral ischemia. Suppressor Down regulation Up regulation Down regulation Driver Marker . REF000720 ICD-11: 8B10 Cerebral ischemia CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00523 L-F001 could restore GPX4 and glutamate-cysteine ligase modifier subunit (GCLM) levels, and significantly deceased Cyclooxygenase (COX-2) levels to rescue the lipid peroxidation imbalance. And L-F001 could reduce RSL3-induced c-Jun N-terminal kinase (JNK) activation, which might be a potential drug target for for the therapy of ferroptosis-related diseases, such as cerebral ischemia. Suppressor Down regulation Up regulation Down regulation Driver Suppressor . REF000720 ICD-11: 8B10 Cerebral ischemia CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00525 Glycyrrhizin (GL) not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by hypoxic-ischemic brain damage (HIBD) in vivo. GL could suppress the occurrence of neuronal ferroptosis and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Male and female neonatal SpragueDawley rats on postpartum day 7 (P7) were provided by SPF Biotechnology (Beijing, China). Each animal was anesthetized with isoflurane (4% for induction, 2% for maintenance), the skin was incised, and the left common carotid artery was exposed. This artery was ligated with a 5-0 suture and cut, and the skin was sutured closed. Next, the pups recovered for 1 h with their mother. Subsequently, the pups were placed in a hypoxia chamber (8% O2 + 92% N2 mixture) for 2 h. After 2 h of hypoxia, the animals were placed back with their dam. REF000721 ICD-11: 8B24 Hypoxic ischemic brain injury CELL10178 Primary Cortical Neuron Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01692 Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. REF000909 ICD-11: 9B10 Cataract CELL00473 Lens Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01691 Melatonin inhibited ferroptosis through the SIRT6/p-Nrf2/GPX4 and SIRT6/COA4/FTH1 pathways to neutralize lipid peroxidation toxicity, which protected cells against ferroptotic stress in vitro and delayed cataract formation caused by UVB exposure in rats. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Six-week-old albino Sprague Dawley (SD) male rats were provided by the Experimental Animal Centre of the Second Affiliated Hospitalof Harbin Medical University. Fifteen minutes before exposure, the rats were anaesthetized by intraperitoneal injection of a mixture of 90 mg/kg ketamine and 15 mg/kg xylazine. Then, tropicamide phenylephrine was dropped in both eyes; at the same time, the rats that received drug treatment were injected subconjunctivally (5 ul/eye) with 500 mM Fer-1, 200 mM MT or the same dose of DMSO used to dissolve the drug using a 28-gauge needle and a Hamilton microinjector. After another 5 min, a single eye of every experimental group rat was exposed to UVB (312 nm) 5 W/m2 for 30 min. Every time, UVB exposure was synchronized with the drug injection, and the frequency was every other day until it was stopped 9 weeks later. REF000909 ICD-11: 9B10 Cataract CELL00473 Lens Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01453 Astragaloside IV (AS-IV) inhibited miR-138-5p expression, subsequently increasing Sirt1/Nrf2 activity and cellular antioxidant capacity to alleviate ferroptosis, resulting decreased cell death, which potentially inhibits the diabetic retinopathy pathological process. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor . REF000688 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE-19 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01454 Astragaloside IV (AS-IV) inhibited miR-138-5p expression, subsequently increasing Sirt1/Nrf2 activity and cellular antioxidant capacity to alleviate ferroptosis, resulting decreased cell death, which potentially inhibits the diabetic retinopathy pathological process. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor . REF000688 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE-19 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01399 Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor . REF000646 ICD-11: BA41 Myocardial infarction CELL10051 cardiomyocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01398 Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor . REF000646 ICD-11: BA41 Myocardial infarction CELL10051 cardiomyocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00400 Fraxetin activated phosphorylation of AKT and Nrf2 nuclear accumulation in Myocardial infarction in vivoandin vitromodels. Moreover, Fra reduced the activity of serum LDH, the accumulation of iron and the MDA level, and increased GSH and glutathione peroxidase 4 (GPX4) in rats with MI. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Male Wistar rats (200-250 g) were obtained from Slac Laboratory Animal Center (Shanghai, China) and kept in cages. The rats were anesthetized with 1% pentobarbital and then lied on its back. Thereafter, the left precordial area of the rats were shaved and disinfected, followed by trachea intubation for artificial ventilation. After the left thoracotomy, the heart was fully exposed and the left coronary artery (LAD) was ligated with a 6-0 prolene suture at 2-3 mm from its origin between the pulmonary artery conus and the left atrial appendage. After 30 min, the suture was gently removed to allow reperfusion for 2 h. REF000544 ICD-11: BA41 Myocardial infarction CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00709 Ptgs2 was positively regulated by Hif1a and contributed to ferroptosis-dependent myocardial injury and inflammation. Furthermore, Atorvastatin protects against ferroptosis and inflammation induced by CME via the Hif1a/Ptgs2 pathway. Suppressor Down regulation Down regulation Up regulation Driver Marker Rats were anesthetized intraperitoneally with 3% pentobarbital sodium (40 mg/kg). After mechanical ventilation, the rats were subjected to a thoracotomy to expose the hearts and ascending aorta. Finally, the ascending aorta was occluded for 10 s, and 8,000 polyester microspheres (diameter 42 um, Biosphere Medical, Rockland, MA, United States ) were injected into the left ventricle at the same time, while the sham-operated rats received the same dosage of normal saline instead. Forin vivotreatment, rats were treated with recombinant adeno-associated virus 9 (rAAV9)-GFP-shPtsg2 (Hanbio, Shanghai, China) or rAAV9-GFP-shHif1a (Genechem, Shanghai, China) at a dose of 1 x 1012 VG in 200 uL salineviaa single tail vein before CME. Deferoxamine (DFO) was purchased from Selleck (Shanghai, China) and administered intraperitoneally at a dose of 100 mg/kg for 7 days before CME. ATV (Pfizer, New York, United Kingdom) was administered intragastrically at a dose of 10 mg/kg for 7 days before CME. REF000926 ICD-11: BA41 Coronary microembolization CELL10136 myocardial tissues Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00334 ENPP2 was transcriptionally regulated by FoxO4 to protect cardiomyocytes from doxorubicin-induced cardiotoxicity by inhibiting ferroptosis. In addition, the inhibitory effects of ENPP2 on Dox-induced ferroptosis were significantly reduced by FoxO4 overexpression, as demonstrated by increased Fe2+ and lipid ROS activity levels, decreased SLC7A11, GPX4 and FPN1 expression, and increased NOX4 expression, which were observed following FoxO4 overexpression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000460 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00695 KLF15 siRNA impeded the beneficial roles of elabela (ELA) in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor . REF000918 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL10163 adventitial fibroblasts (AFs) Ferroptosis (hsa04216) Cell ferroptosis
unique01339 Lapatinib (LAP) inhibited the cell viability and exacerbated cell injury induced by doxorubicin, as well as increased cell apoptosis. LAP aggravated Dox-induced cardiotoxicity by promoting oxidative stress and ferroptosis in cardiomyocytes via PI3K/AKT-mediated mitochondrial dysfunction. Moreover, GPX4 expression was decreased and ASCL4 level was higher following DOX treatment or the combination therapy of LAP and DOX. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000606 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00030 H9C2 PI3K-Akt signaling pathway (hsa04151); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01340 Lapatinib (LAP) inhibited the cell viability and exacerbated cell injury induced by doxorubicin, as well as increased cell apoptosis. LAP aggravated Dox-induced cardiotoxicity by promoting oxidative stress and ferroptosis in cardiomyocytes via PI3K/AKT-mediated mitochondrial dysfunction. Moreover, GPX4 expression was decreased and ASCL4 level was higher following DOX treatment or the combination therapy of LAP and DOX. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000606 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00030 H9C2 PI3K-Akt signaling pathway (hsa04151); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00693 KLF15 siRNA impeded the beneficial roles of elabela (ELA) in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor . REF000918 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL10163 adventitial fibroblasts (AFs) Ferroptosis (hsa04216) Cell ferroptosis
unique00694 KLF15 siRNA impeded the beneficial roles of elabela (ELA) in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor . REF000918 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL10163 adventitial fibroblasts (AFs) Ferroptosis (hsa04216) Cell ferroptosis
unique01286 Doxorubicin treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. And miR-7-5p inhibits DOX-induced ferroptosis in cardiomyocytes by directly repressing TFRC. Inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury. Inducer Up regulation Up regulation Up regulation Driver Marker/Suppressor/Driver Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks. REF000540 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00286 AC16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01287 Doxorubicin treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. And miR-7-5p inhibits DOX-induced ferroptosis in cardiomyocytes by directly repressing TFRC. Inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury. Inducer Up regulation Up regulation Up regulation Driver Marker/Suppressor/Driver Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks. REF000540 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00286 AC16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01288 Doxorubicin treatment resulted in the upregulation of methyltransferase-like 14 (METTL14), which catalyzes the m6A modification of the long non-coding RNA KCNQ1OT1, a miR-7-5p sponge. And miR-7-5p inhibits DOX-induced ferroptosis in cardiomyocytes by directly repressing TFRC. Inhibiting ferroptosis mediated by a METTL14/KCNQ1OT1/miR-7-5p positive feedback loop in cardiomyocytes could provide a new therapeutic approach to control DOX-induced cardiac injury. Inducer Down regulation Up regulation Down regulation Suppressor Marker/Suppressor/Driver Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks. REF000540 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00286 AC16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01736 Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group. REF000954 ICD-11: BC81.3 Atrial fibrillation CELL00548 HL-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01735 Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group. REF000954 ICD-11: BC81.3 Atrial fibrillation CELL00548 HL-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01734 Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group. REF000954 ICD-11: BC81.3 Atrial fibrillation CELL00548 HL-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01733 Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group. REF000954 ICD-11: BC81.3 Atrial fibrillation CELL00548 HL-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01539 The exosome inhibitor GW4869 reduced ferroptosis, fibrosis, and inflammation and improved histological and electrophysiological remodeling. Pacing-CF-exos highly expressed miR-23a-3p by informatics analysis and experimental verification. Inhibitor- miR-23a-3p protected h9c2 cells from ferroptosis accompanying with upregulation of SLC7A11. The development of atrial fibrillation (AF) in a persistent direction could be prevented by intervening with exosomal miRNAs to reduce oxidative stress injury and ferroptosis. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Eighteen beagles, randomly divided into three groups, both sexes and an average age of 1 year, weighing 7.5 ± 1.5 kg, were used for the study as follows: Sham group (n = 6), Pacing group (n = 6), and GW4869 + Pacing group (n = 6). Each beagle canine was given an intramuscular injection of 25 mg/kg ketamine sulfate before being premedicated with pentobarbital sodium (30 mg/kg, intravenous injection) and ventilated with room air by a respirator (MAO01746, Harvard Apparatus Holliston, United States). Venous access was established to supply saline (50-100 mL/h) or pentobarbital sodium (2.5 mg/kg/h). REF000755 ICD-11: BC81.3 Atrial fibrillation CELL00030; CELL10166 H9C2; CFs Ferroptosis (hsa04216) Cell ferroptosis
unique01174 Ferric ammonium citrate(FAC) can induce a decrease in foam cell activity rather than macrophage activity, increase lipid ROS levels, decrease GPX4 expression and inhibit SIRT1 expression. Activation of SIRT1 can inhibit the ferroptosis and IL-1 and IL-18 levels of foam cells in excess iron by autophagy, providing a novel therapeutic target for atherosclerosis(AS). Inducer Down regulation Down regulation Up regulation Suppressor Suppressor A total of 20 male Apoe-/-mice (6-8 weeks of age, 18-22 g) were purchased from Charles River (Beijing, China). Mice were randomly assigned to a control group (normal diet: 4% fat, cholesterol free, and sodium cholate) and an AS group (high-fat diet: 20% fat, 1.25% cholesterol, and 0.5% sodium cholate). REF000409 ICD-11: BD40 Atherosclerosis CELL00038 THP-1 Autophagy (hsa04140); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00542 Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis. Suppressor Down regulation Down regulation Up regulation Driver Marker/Suppressor Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg). REF000751 ICD-11: CB03 Chronic obstructive pulmonary disease complicated with atherosclerosis CELL10050; CELL00342 Human bronchial epithelial (HBE) cells; MRC-5 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00541 Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis. Suppressor Down regulation Down regulation Up regulation Driver Driver Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg). REF000751 ICD-11: CB03 Chronic obstructive pulmonary disease complicated with atherosclerosis CELL10050; CELL00342 Human bronchial epithelial (HBE) cells; MRC-5 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00137 Arsenic induces rat liver nonalcoholic steatohepatitis (NASH) and Ferroptosis via interacting between Mitofusin-2 with IRE1. NaAsO2 increases IRE1 and Mfn2 expression, subsequently led to upregulated ACSL4 expression and 5-HETE via the directly combination Mfn2 with IRE1, ultimately induced ferroptotic cell death. Inducer Up regulation Up regulation Up regulation Driver Driver Adult male Sprague-Dawley rats (300 g-350 g, specific pathogen free) were obtained from Institute of Genome Engineered Animal Models for Human Disease of Dalian Medical University (Dalian, China). To explore the influence of NaAsO2 (CAS No.7784-46-5, Sigma-Aldrich, USA) on the liver, the rats were subjected to NaAsO2 at the dosage of 0, 2.5, and 5 mg/kg by gavage for 9 months. The control group was gavaged with distilled water as vehicle. REF000194 ICD-11: DB92 Nonalcoholic steatohepatitis CELL00304 L-02 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00136 Arsenic induces rat liver nonalcoholic steatohepatitis (NASH) and Ferroptosis via interacting between Mitofusin-2 with IRE1. NaAsO2 increases IRE1 and Mfn2 expression, subsequently led to upregulated ACSL4 expression and 5-HETE via the directly combination Mfn2 with IRE1, ultimately induced ferroptotic cell death. Inducer Up regulation Up regulation Up regulation Driver Driver Adult male Sprague-Dawley rats (300 g-350 g, specific pathogen free) were obtained from Institute of Genome Engineered Animal Models for Human Disease of Dalian Medical University (Dalian, China). To explore the influence of NaAsO2 (CAS No.7784-46-5, Sigma-Aldrich, USA) on the liver, the rats were subjected to NaAsO2 at the dosage of 0, 2.5, and 5 mg/kg by gavage for 9 months. The control group was gavaged with distilled water as vehicle. REF000194 ICD-11: DB92 Nonalcoholic steatohepatitis CELL00304 L-02 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00248 Dehydroabietic acid (DA) inhibited ferroptosis and increased the expression of key genes such as ferroptosis suppressor protein 1 (FSP1) in vitro and vivo. In all, DA may bind with Keap1, activate Nrf2-ARE, induce its target gene expression, inhibit ROS accumulation and lipid peroxidation, and reduce HFD-induced nonalcoholic fatty liver disease (NAFLD). Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor The male C57BL/6J mice (6-8 weeks, Beijing Vital River Laboratory Animal Technology Co., Ltd., China) were exposed to 12 h of light and darkness at temperature (22 ± 2 ), humidity (55%) with free access to water and food. All the mice were acclimated for 1 week before the experiment, then the mice were fed normal chow diet (NCD) and high-fat diet (HFD, D12492) for 12 weeks. The HFD group was divided into 3 groups (HFD, low dose of DA (DA-L, 10 mg/kg/d), high dose of DA (DA-H, 20 mg/kg/d),n = 8)). DA was administered by gavage for 9 weeks, and 0.5% CMC-Na was administered by NCD and HFD. REF000324 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00057; CELL00304 HEK293T; HL7702 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Pathways in cancer (hsa05200) Cell ferroptosis
unique00232 The protein expressions of SREBP1 and its downstream targets ACC1, FASN and SCD1 were all increased in fructose-treated AML12 hepatocytes, which demonstrates fructose mediated upregulation of SREBP1. MiR-33-5p (miR-33) was identified as the key miRNA responsible for SREBP1 regulation upon fructose intake, which was validated by in vitro transfection assay. Collectively, fructose-induced oxidative damage induces ferroptosis, and miR-33 could be used as a serological biomarker of fructose-induced non-alcoholic fatty liver disease (NAFLD). Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks). REF000298 ICD-11: DB92 Non-alcoholic fatty liver disease CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00231 The protein expressions of SREBP1 and its downstream targets ACC1, FASN and SCD1 were all increased in fructose-treated AML12 hepatocytes, which demonstrates fructose mediated upregulation of SREBP1. MiR-33-5p (miR-33) was identified as the key miRNA responsible for SREBP1 regulation upon fructose intake, which was validated by in vitro transfection assay. Collectively, fructose-induced oxidative damage induces ferroptosis, and miR-33 could be used as a serological biomarker of fructose-induced non-alcoholic fatty liver disease (NAFLD). Inducer Up regulation Down regulation Down regulation Driver Suppressor Four-week-old male and female C57BL/6N mice were obtained from the Central Lab Animal Inc. (Seoul, South Korea) and housed in 42 x 27 x 15 cm polycarbonate cages (six mice per cage). The animals were assigned into either the control group (n = 12; six mice per sex) or fructose intervention group (n = 12; six mice per sex). After a week of acclimation, the fructose group was subjected to 34% fructose in deionized water (wt:vol) over six weeks to induce NAFLD conditions as previously described.11 To note, compared to conventional sugary beverages (e.g., soft drinks), the supplementation level of fructose is higher (11% vs. 34%) to induce liver damage markers within a reasonable intervention time range (i.e., 6 weeks). REF000298 ICD-11: DB92 Non-alcoholic fatty liver disease CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00934 Sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. ZFP36 plasmid markedly upregulated, whereas FBXW7 plasmid apparently downregulaed, ferritin and NCOA4 expression in sorafenib-treated HSC-LX2 cells. The study identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis. Inducer Down regulation Up regulation Down regulation Suppressor Driver Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation. REF000104 ICD-11: DB93 Liver fibrosis CELL10073 HSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00935 Sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. ATG16L1 plasmid eliminated the inhibitory action of ZFP36 plasmid on ferroptosis, and FBXW7 plasmid enhanced the effect of ATG16L1 plasmid on autophagy. ZFP36 plasmid markedly upregulated, whereas FBXW7 plasmid apparently downregulaed, ferritin and NCOA4 expression in sorafenib-treated HSC-LX2 cells. The study identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis. Inducer Up regulation Up regulation Up regulation Driver Driver Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation. REF000104 ICD-11: DB93 Liver fibrosis CELL10073 HSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00933 Sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. ZFP36 plasmid markedly upregulated, whereas FBXW7 plasmid apparently downregulaed, ferritin and NCOA4 expression in sorafenib-treated HSC-LX2 cells. The study identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis. Inducer Up regulation Up regulation Up regulation Driver Driver Fifty-six 8-week-old male C57BL/6 mice were obtained from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Controls underwent a sham operation that consisted of exposure, but not ligation, of the common bile duct. Erastin (30 mg/kg, once every other day) and sorafenib (10 mg/kg, once every other day) were suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. VA-Lip-control-vector and VA-Lip-Zfp36-plasmid (0.75 mg/kg) were administered intravenously 3 times a week for 2 weeks after the BDL operation. REF000104 ICD-11: DB93 Liver fibrosis CELL10073 HSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00866 Sorafenib treatment remarkably upregulated NCOA4 expression, and 3 critical events including ELAVL1 upregulation, ferritinophagy activation, and ferroptosis induction occur in primary human HSCs from fibrotic patients receiving sorafenib monotherapy. ELAVL1 is a potential target for the treatment of liver fibrosis. Inducer Up regulation Up regulation Up regulation Driver Driver Eight-week-old male C57BL/6 mice were purchased from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Sorafenib (10 mg/kg, once every other day) was suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. The livers were collected 2 weeks after surgery under general anesthesia. REF000046 ICD-11: DB93 Liver fibrosis CELL10073 HSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell autophagy
unique01810 Empagliflozin has a promising protective effect against BLM-induced liver fibrosis in rats by enhancing autophagy and mitigating ferroptosis, inflammation, and ER stress via modulating the Sesn2/AMPK/Nrf2/HO-1 signaling pathway. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor After a one-week acclimatization period, rats were randomly divided into four experimental groups of six rats each. Group I (the control group) received saline intraperitoneally in the same manner as BLM injections, as well as 1% carboxymethyl cellulose (CMC) orally in the same manner as EMPA. Group II (the BLM-treated group) received BLM (15 mg/kg) intraperitoneally three times per week for four successive weeks in order to induce pulmonary fibrosis. Group III (the EMPA-treated group) received EMPA dissolved in 1% CMC orally via oral gavage at a dose of 10 mg/kg/day throughout the experimental period. Group IV (the combined EMPA and BLM-treated group) received EMPA (10 mg/kg) orally via oral gavage seven days before BLM administration and continued for four weeks after BLM injection. REF001042 ICD-11: DB93 Liver fibrosis CELL10040 Liver tissues Autophagy (hsa04140); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell autophagy
unique00269 The gut microbiota metabolite capsiate enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal ischemia/reperfusion (I/R) injury, providing a potential avenue for the management of intestinal ischemia/reperfusion (I/R) injury. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Six- to eight-week-old specific pathogen-free male C57BL/6 mice were purchased from the animal center of Nanfang Hospital of Southern Medical University (Guangzhou, China). The mice were anesthetized with isoflurane. A noninvasive microvascular artery clip was placed on the superior mesenteric artery (SMA) for 60 min, and the clip was removed for reperfusion for 2 hours. During the study period, body temperature was maintained at 37 with a heating pad, and liquid resuscitation was performed by subcutaneous injection with 0.5 ml of physiological saline immediately after reperfusion. REF000369 ICD-11: DB98 Intestinal ischemia/reperfusion injury CELL10153 small intestinal organoids Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01795 The inhibition of MALT1 can reduce ischemia/reperfusion-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor The surgical procedure for establishing the myocardial I/R injury rat model was carried out as we did before. Briefly, a left thoracotomy was performed in the fourth intercostal space and the heart was exposed via opening thepericardium. The left coronary artery was surrounded with a 4-0 silk suture and a snare was formed by passing both ends of the suture via a short polyethylene tubing. Blockage of the coronary artery was conducted via clamping the snare against the heart surface. Reperfusion was performed by release of the snare. The sham group conducted the same procedure but without ischemia (the snare was not tightened). To establish the I/R injury model, the rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion. At the end, the blood and hearts were collected for assay of the creatine kinase(CK) activity and infarct size to determine the success of I/R injury model. To explore the role of MALT1 in myocardial I/R injury the underlying mechanisms, three sets of experiment were performed. REF001021 ICD-11: DB98 Myocardial ischemia/reperfusion CELL00030 H9c2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01794 The inhibition of MALT1 can reduce ischemia/reperfusion-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction. Suppressor Down regulation Up regulation Down regulation Driver Suppressor The surgical procedure for establishing the myocardial I/R injury rat model was carried out as we did before. Briefly, a left thoracotomy was performed in the fourth intercostal space and the heart was exposed via opening thepericardium. The left coronary artery was surrounded with a 4-0 silk suture and a snare was formed by passing both ends of the suture via a short polyethylene tubing. Blockage of the coronary artery was conducted via clamping the snare against the heart surface. Reperfusion was performed by release of the snare. The sham group conducted the same procedure but without ischemia (the snare was not tightened). To establish the I/R injury model, the rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion. At the end, the blood and hearts were collected for assay of the creatine kinase(CK) activity and infarct size to determine the success of I/R injury model. To explore the role of MALT1 in myocardial I/R injury the underlying mechanisms, three sets of experiment were performed. REF001021 ICD-11: DB98 Myocardial ischemia/reperfusion CELL00030 H9c2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00726 Baicalein alleviated osteoarthritis (OA) development by improving the activity of AMPKa/Nrf2/HO-1 signaling to inhibit chondrocyte ferroptosis, revealing baicalein to be a potential therapeutic strategy for OA. AMPKa preserved Nrf2 abundance in chondrocytes and promoted Nrf2 into nucleus by promoting Keap1 degradation Suppressor Down regulation Up regulation Down regulation Driver Suppressor C57BL/6J (WT) mice (8 weeks old, male) were purchased from Nanjing Medical university, and AMPK-KO mice were purchased from Shanghai Model Organisms. They were used to create an OA model by destabilization of the medial meniscus surgery (DMM) (n = 6 per group). Briefly, after the mice were anaesthetized, a medial articular incision was made to expose the leftjoint cavity, and then the tibial collateral ligament was transected. Finally, the articular incision was closed. In the control group, only the joint cavity was opened. One week after surgery, 1 mg/kg baicalein (MCE, HY-N0196) per knee, 1 mg/kg ML385 (MCE, HY-100523) per knee, 1 mg/kg AICAR (MCE, HY-13417) per knee or 1 mg/kg of the ferroptosis inhibitor ferrostatin-1 (Fer-1, MCE, HY-100579) was injected into the joint cavity of the mice once a week. Meanwhile, saline was injected into the control group. Mice were sacrificed after surgery 10 weeks. REF000943 ICD-11: FA05 Osteoarthritis CELL10008 chondrocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00725 Baicalein alleviated osteoarthritis (OA) development by improving the activity of AMPKa/Nrf2/HO-1 signaling to inhibit chondrocyte ferroptosis, revealing baicalein to be a potential therapeutic strategy for OA. AMPKa preserved Nrf2 abundance in chondrocytes and promoted Nrf2 into nucleus by promoting Keap1 degradation Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor C57BL/6J (WT) mice (8 weeks old, male) were purchased from Nanjing Medical university, and AMPK-KO mice were purchased from Shanghai Model Organisms. They were used to create an OA model by destabilization of the medial meniscus surgery (DMM) (n = 6 per group). Briefly, after the mice were anaesthetized, a medial articular incision was made to expose the leftjoint cavity, and then the tibial collateral ligament was transected. Finally, the articular incision was closed. In the control group, only the joint cavity was opened. One week after surgery, 1 mg/kg baicalein (MCE, HY-N0196) per knee, 1 mg/kg ML385 (MCE, HY-100523) per knee, 1 mg/kg AICAR (MCE, HY-13417) per knee or 1 mg/kg of the ferroptosis inhibitor ferrostatin-1 (Fer-1, MCE, HY-100579) was injected into the joint cavity of the mice once a week. Meanwhile, saline was injected into the control group. Mice were sacrificed after surgery 10 weeks. REF000943 ICD-11: FA05 Osteoarthritis CELL10008 chondrocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00374 D-mannose alleviates osteoarthritis (OA) progression by suppressing HIF-2a-mediated chondrocyte sensitivity to ferroptosis. Overexpression of HIF-2a in chondrocytes by Ad- Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. Also, the RNA and protein levels of the two key ferroptosis suppressors, Gpx4 and Slc7a11, were increased in Dmannosetreated chondrocytes. Suppressor Down regulation Up regulation Down regulation Driver Suppressor C57BL/6 J mice (8 weeks old, female) were purchased from Dossy Experimental Animal Limited Company (Chengdu, China). For surgery, mice were anaesthetized with pentobarbital sodium (100 mg/kg, injected intraperitoneally) and subjected to unilateral ACLT procedures. 28 The sham group received a skin incision and suturing without patellar dislocation or ligament transection. For virus injection, mice were intraarticularly injected with 1 x 109 pfu (8 ul) of mock or AdEpas1 virus after one week of surgery. For Fer1 (MCE, Monmouth Junction, HY100579) injection, mice were intraarticularly injected with 1 mg/kg Fer1 or with vehicle two weeks after surgery, the injection was repeated once a week. REF000508 ICD-11: FA05 Osteoarthritis CELL10008 chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00229 Ferric citrate induced ferroptosis in C2C12 cells, as well as impaired their differentiation from myoblasts to myotubes. Iron overload upregulated the expression of P53, which subsequently repressed the protein level of Slc7a11 (solute carrier family 7, member 11), a known ferroptosis-related gene. Targeting iron accumulation and ferroptosis might be a therapeutic strategy for treating sarcopenia. Inducer Up regulation Down regulation Down regulation Driver Suppressor The 8-week- and 40-week-old male SAMP8 mice were purchased from the model animal research center of Zhishan Institute of Healthcare Research Co., Ltd. (Beijing, China). All the mice were kept in an SPF grade animal facility at 24 with a relative humidity of 50%-60%, and in a light/dark cycle of 12 h/12 h. REF000296 ICD-11: FB32 Sarcopenia CELL00546 C2C12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00249 Carbonyl cyanide-m-chlorophenyl-hydrazine (CCCP) is a mitophagy agonist. Through adding mitophagy agonist CCCP to osteoblasts, we found the increase of ROS and lipid peroxidation while GPX4 decreased. FtMt inhibited the occurrence of ferroptosis in osteoblasts by reducing oxidative stress caused by excess ferrous ions, and FtMt deficiency induced mitophagy in the pathogenesis of type 2 diabetic osteoporosis (T2DOP). Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Forty-five SD rats (3 months old, 200 ± 20 g) were obtained from the Department of Experimental Animals in China Medical University (Animal Certificate Number: SCXK (Liaoning) 2008-0005). Fifteen rats grew as control while other thirty rats were established T2DOP model. The model rats were given a high-fat feed and 12 h/day water for 2 months. Then streptozotocin was intraperitoneally injected at 30 mg/kg. Seventy-two hours later, the model was successfully established when insulin sensitivity index decreased and fasting plasma glucose exceeded 7.8 mmol/L. Then all rats continue grew 3 months to cause osteoporosis. Thirty model rats were divided into two groups. One was fifteen T2DOP rats only, and other was fifteen T2DOP rats with deferoxamine (DFO) treatment (60 mg/kg/day, intraperitoneally inject, last for the last 1 month). REF000326 ICD-11: FB83 Type 2 diabetic osteoporosis CELL00269 hFOB 1.19 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00266 Guizhi Fuling Capsule (GFC) may attenuate estrogen-induced endometrial hyperplasia in mice through triggering ferroptosis via inhibiting p62 (SQSTM1)-Keap1-NRF2 pathway. GFC might act as a promising traditional Chinese medicine to treat endometrial hyperplasia. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor Female C57BL/6 mice (8-week-old) were purchased from Model Animal Research Center of Nanjing University (Nanjing, China). Fifteen mice were randomly divided into three groups: Olive oil group, Estradiol group and Estradiol + IKE group. The Estradiol group was subcutaneously injected estradiol (50 ug/kg/day), Estradiol + IKE group was subcutaneously injected estradiol and intraperitoneally injected IKE (50 mg/kg) for 21 days, while the Olive oil group received the same volume of olive oil. In the experiment of exploring the improvement of GFC to EH, twenty mice were randomly divided into four groups: Olive oil group, Estradiol group, 75 mg/kg GFC group and 150 mg/kg GFC group. Except for Olive oil group, mice were subcutaneously daily injected with estradiol (50 ug/kg/day) for 21 days, while the Olive oil group received the same volume of olive oil. 75 mg/kg GFC group and 150 mg/kg GFC group were treated with GFC intragastrical administration. REF000367 ICD-11: GA16 Endometrial hyperplasia CELL10160 Uterine tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00267 Guizhi Fuling Capsule (GFC) may attenuate estrogen-induced endometrial hyperplasia in mice through triggering ferroptosis via inhibiting p62 (SQSTM1)- Keap1-NRF2 pathway. GFC might act as a promising traditional Chinese medicine to treat endometrial hyperplasia. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor Female C57BL/6 mice (8-week-old) were purchased from Model Animal Research Center of Nanjing University (Nanjing, China). Fifteen mice were randomly divided into three groups: Olive oil group, Estradiol group and Estradiol + IKE group. The Estradiol group was subcutaneously injected estradiol (50 ug/kg/day), Estradiol + IKE group was subcutaneously injected estradiol and intraperitoneally injected IKE (50 mg/kg) for 21 days, while the Olive oil group received the same volume of olive oil. In the experiment of exploring the improvement of GFC to EH, twenty mice were randomly divided into four groups: Olive oil group, Estradiol group, 75 mg/kg GFC group and 150 mg/kg GFC group. Except for Olive oil group, mice were subcutaneously daily injected with estradiol (50 ug/kg/day) for 21 days, while the Olive oil group received the same volume of olive oil. 75 mg/kg GFC group and 150 mg/kg GFC group were treated with GFC intragastrical administration. REF000367 ICD-11: GA16 Endometrial hyperplasia CELL10160 Uterine tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00405 Renal REV-ERB protein was significantly increased in aristolochic acid I-treated mice. Furthermore, knockdown of Rev-erb by siRNA or SR8278 (a REV-ERB antagonist) treatment attenuated ALI-induced ferroptosis in mRTECs. SR8278 treatment enhanced the cell survival and GPX4 expression in ALI-treated mRTECs. Taken together, small molecule antagonism of REV-ERB alleviates aristolochic acid I-induced renal injury probably through inhibiting ferroptosis in mice. Inducer Up regulation Down regulation Down regulation Driver Suppressor Wild-type C57BL/6 mice (eight-week-old, male) were obtained from SPF Biotechnology (Beijing, China). Three sets of animal experiments were performed. In the first set of experiments, male wild-type mice (eight-week-old) were randomly assigned to three groups (n = 6 per group): control group, 2.5 mg/kg AAI group, and 5 mg/kg AAI group. The AAI groups of mice were intraperitoneally injected with AAI (2.5 or 5 mg/kg) once daily for 5 days. The control group of mice were treated with vehicle (corn oil). In the second set of experiments, male Rev-erbfl/fl and Rev-erbkKO mice (eight-week-old) were treated with AAI (5 mg/kg) or vehicle once daily for 5 days by intraperitoneal injection. In the third set of experiments, male wild-type mice (eight-week-old) were randomly divided into the following four groups (n = 6 per group): AAI + SR8278, AAI + DFO, AAI, and vehicle. REF000555 ICD-11: GB55 Aristolochic acid nephropathy CELL10151; CELL10149 mRTECs; M4100-57 Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00406 Renal REV-ERB protein was significantly increased in aristolochic acid I-treated mice. Furthermore, knockdown of Rev-erb by siRNA or SR8278 (a REV-ERB antagonist) treatment attenuated ALI-induced ferroptosis in mRTECs. SR8278 treatment enhanced the cell survival and GPX4 expression in ALI-treated mRTECs. Taken together, small molecule antagonism of REV-ERB alleviates aristolochic acid I-induced renal injury probably through inhibiting ferroptosis in mice. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Wild-type C57BL/6 mice (eight-week-old, male) were obtained from SPF Biotechnology (Beijing, China). Three sets of animal experiments were performed. In the first set of experiments, male wild-type mice (eight-week-old) were randomly assigned to three groups (n = 6 per group): control group, 2.5 mg/kg AAI group, and 5 mg/kg AAI group. The AAI groups of mice were intraperitoneally injected with AAI (2.5 or 5 mg/kg) once daily for 5 days. The control group of mice were treated with vehicle (corn oil). In the second set of experiments, male Rev-erbfl/fl and Rev-erbkKO mice (eight-week-old) were treated with AAI (5 mg/kg) or vehicle once daily for 5 days by intraperitoneal injection. In the third set of experiments, male wild-type mice (eight-week-old) were randomly divided into the following four groups (n = 6 per group): AAI + SR8278, AAI + DFO, AAI, and vehicle. REF000555 ICD-11: GB55 Aristolochic acid nephropathy CELL10151; CELL10149 mRTECs; M4100-57 Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00234 Legumain promotes chaperone-mediated autophagy of GPX4 therefore facilitates tubular ferroptosis in acute kidney injury (AKI). Legumain inhibitor RR-11a attenuates ferroptosis and tubular injury induced by ischemia-reperfusion injury (IRI). Suppressor Down regulation Up regulation Down regulation Driver Suppressor The genetic background of embryonic stem cells and the Flp mice used in this experiment was C57BL/6. Mice were randomly separated into experimental groups and control groups. (1) Bilateral IRI: mice (male, 8-10 weeks old) on the lgmnKO background or littermate control mice were anesthetized by an intraperitoneal (i.p.) injection of chloral hydrate and placed on a warm pad to retain their body temperature. A bilateral flank incision was made, both sides of the renal vessels were occluded with clamps for 40 min followed by removing the clamps to induce blood reperfusion. The same procedure was performed in the control group without vessel clamping. (2) Nephrotoxic folic acid-induced AKI: mice (female, 12-14 weeks old) received a single i.p. injection of folic acid at 250 mg/kg in 0.3 mol/L sodium bicarbonate or the vehicle. For therapeutic experiments, RR-11a was freshly dissolved in saline. Mice were administered an i.p. injection of 20 mg/kg RR-11a or the vehicle before ischemia. REF000302 ICD-11: GB60 Acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00439 Isoliquiritigenin (ISL) attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Male C57BL/6 mice (aged 6-8 weeks and weighing 22-25g) were obtained from the Experimental Animal Center, Sichuan Provincial Peoples Hospital, and were fed a standard laboratory diet. LPS and ISL were dissolved in normal saline and 0.5% Tween-20/saline, respectively. AKI mice were developed by intraperitoneal (i.p.) LPS injection. A total of 30 mice were randomly divided into six groups (n = 5): control, ISL, Fer, LPS, LPS plus ISL, and LPS plus Fer. An intraperitoneal injection of LPS (10 mg/kg) was made to induce septic AKI. ISL was administered via gavage at 50 mg/kg 30 min before LPS injection. Mice were dosed intraperitoneally with Fer (Ferrostatin-1, SML0583, Sigma-Aldrich, St. Louis, MO) at 5 mg/kg. Mice were sacrificed by cervical dislocation 8 h after LPS injection. Kidney tissue and serum samples were collected concurrently. REF000585 ICD-11: GB60 Acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01762 A JAK2 inhibitor Fedratinib downregulated TRIM21 expression and reduced damage both in vivo and in vitro, which is correlated with the upregulation of GPX4. Our study showed that loss of TRIM21 could alleviate ferroptosis induced by I/R, revealed the mechanism of ubiquitination degradation of GPX4 by TRIM21 and suggested TRIM21 is a potential target for the treatment of acute kidney injury (AKI). Suppressor Down regulation Up regulation Down regulation Driver Suppressor Mice were fasted for 12 h and anesthetized (1% pentobarbital sodium, i.p.) before surgery. Bilateral renal pedicles were clamped for 30 min, then remove the arterial clamps. The sham groups were treated in the same way, except for the clamping of the renal pedicle. Blood samples were collected 24 h after reperfusion, mice were killed, and kidney were collected for follow-up experiments. Fedratinib (5 mg/kg body weight) was injected (i.p.) into mice 24 h once in advance before surgery. REF000990 ICD-11: GB60 Acute kidney injury CELL00093 HK-2 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00076 Pretreatment of paricalcitol could also alleviated Erastin (an inducer of ferroptosis) induced cell death in HK-2 cell. Ferroptosis plays an important role in cisplatin induced acute kidney injury. VDR activation can protect against cisplatin induced renal injury by inhibiting ferroptosis partly via trans-regulation of GPX4. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor A total of 72 male C57BL/6 mice were purchased from Slyke jingda Biotechnology Company. They were randomly divided into five groups: Control group (n = 8), Cisplatin (20 mg/kg dissolved in saline) only group (n = 16), Cisplatin + paricalcitol (0.2 ug/kg dissolved in sterile water for injection and 20% propylene glycol) group (n = 16), Cisplatin + DMSO group (n = 16), Cisplatin + Fer-1 (5 mg/kg dissolved in DMSO) group (n = 16), were administered intraperitoneally. Cisplatin was injected once to mice, while Fer-1 was injected once an hour before cisplatin, and paricalcitol was injected once daily for five consecutive days before cisplatin. Each eight mice were sacrificed at 48 h and 72 h, respectively after cisplatin injection, and eight mice in the control group were sacrificed together with mice at 72 h. REF000129 ICD-11: GB60 Acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00543 Entacapone upregulates p62 (SQSTM1) expression and affects the p62-KEAP1-NRF2 pathway, thereby upregulating nuclear translocation of NRF2. This action results in increased expression of the downstream SLC7A11, and significant suppression of oxidative stress and ferroptosis. Entacapone may serve as a novel strategy to improve treatment of, and recovery from, ischemia/reperfusion-induced acute kidney injury (I/R-AKI). Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Male C57BL/6 mice (8-10 weeks; 20-25 g) were purchased from LINGCHANG BIOTECH (China). Mice were divided into four groups: (i) sham, (ii) I/R, (iii) I/R+entacapone, and (iv) I/R + Fer-1. Entacapone (15 mg/kg bodyweight) was dissolved in sodium carboxymethyl cellulose (0.5%) and administered (i.g.) to mice. Mice in the sham group were administered (i.g.) an equal volume of solvent. Fer-1 was dissolved in 5% dimethyl sulfoxide + 30% polyethylene glycol-400 + 60% saline and injected (i.p.). Mice were treated three times per day for 3 days in advance. Before I/R, mice were fasted for 12 h and anesthetized (1% pentobarbital sodium, i.p.). The abdomen was exposed and bilateral renal pedicles were clamped to induce renal I/R. After 25 min, the arterial clamps were removed. A body temperature of 37 was maintained throughout the procedure. The sham group underwent the same procedure except for clamping of the renal pedicle. Mice were killed 24 h after reperfusion, and kidney and blood samples were collected for experimentation. REF000756 ICD-11: GB60 Acute kidney injury CELL00093 HK2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00544 Entacapone upregulates p62 (SQSTM1) expression and affects the p62- KEAP1-NRF2 pathway, thereby upregulating nuclear translocation of NRF2. This action results in increased expression of the downstream SLC7A11, and significant suppression of oxidative stress and ferroptosis. Entacapone may serve as a novel strategy to improve treatment of, and recovery from, ischemia/reperfusion-induced acute kidney injury (I/R-AKI). Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor Male C57BL/6 mice (8-10 weeks; 20-25 g) were purchased from LINGCHANG BIOTECH (China). Mice were divided into four groups: (i) sham, (ii) I/R, (iii) I/R+entacapone, and (iv) I/R + Fer-1. Entacapone (15 mg/kg bodyweight) was dissolved in sodium carboxymethyl cellulose (0.5%) and administered (i.g.) to mice. Mice in the sham group were administered (i.g.) an equal volume of solvent. Fer-1 was dissolved in 5% dimethyl sulfoxide + 30% polyethylene glycol-400 + 60% saline and injected (i.p.). Mice were treated three times per day for 3 days in advance. Before I/R, mice were fasted for 12 h and anesthetized (1% pentobarbital sodium, i.p.). The abdomen was exposed and bilateral renal pedicles were clamped to induce renal I/R. After 25 min, the arterial clamps were removed. A body temperature of 37 was maintained throughout the procedure. The sham group underwent the same procedure except for clamping of the renal pedicle. Mice were killed 24 h after reperfusion, and kidney and blood samples were collected for experimentation. REF000756 ICD-11: GB60 Acute kidney injury CELL00093 HK2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00433 Downregulation of Cx43 expression by gap27 reduced acute kidney injury in the animal model by inhibiting cisplatin-induced ferroptosis. Therefore, our results indicated that downregulation of Cx43 can inhibit ferroptosis by restoring the level of SLC7A11 in the system xctransporter and alleviate cisplatin-induced acute kidney injury. Suppressor Down regulation Up regulation Down regulation Driver Suppressor Thirty-two male C57BL/6 mice (20 ± 2) g (Beijing Weitonglihua Experimental Animal Technology Co., Ltd.) were bred in individually ventilated cages (IVC) at SPF conditions, kept on a 12 h light/dark cycle, relative humidity conditions (40-70%) and controlled temperature (24 ± 2 ). After one-week acclimation mice were divided randomly into four groups: control group, cisplatin group (20 mg/kg cisplatin dissolved in saline), cisplatin + Fer-1 group (5 mg/kg Fer-1 dissolved in DMSO), and cisplatin + gap27 group (35 ug/kg gap27 dissolved in DMSO). There were eight animals in each group and 20 mg/kg cisplatin was given to each animal once by intraperitoneal injection except mice in the control group. Fer-1 and gap27 was administered 1 h before the injection of cisplatin. REF000583 ICD-11: GB60 Acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Glutathione metabolism (hsa00480); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01349 mmu_circRNA_0000309 silence mediates drug resistance to germacrone in Diabetic nephropathy mice. mmu_circRNA_0000309 sponges miR-188-3p, and subsequently upregulates GPX4 expression, inactivating ferroptosis-dependent mitochondrial function and podocyte apoptosis. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor C57BL/6J mice were purchased from Three Gorges University (Yichang, China), and C57BL/KsJ and male db/db mice were from Changzhou Cavins Laboratory Animal Co. Ltd. (Changzhou, China). All experiments were approved by the Animal Ethics Committee of Zhejiang Provincial People's Hospital, and performed according to specific institutional and national guidelines. The mice were divided into three groups: control C57BL/6J mice, db/db mice, and germacrone-treated db/db mice (db/db + Ger) (n = 10/each group). The db/db + Ger mice received germacrone treatment at a dosage of 10 mg/kg/day, while C57BL/6J mice and db/db mice had been given the same volumes of 0.9% saline simultaneously. REF000609 ICD-11: GB61 Diabetic nephropathy CELL00564 MPC5 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01350 mmu_circRNA_0000309 silence mediates drug resistance to germacrone in Diabetic nephropathy mice. mmu_circRNA_0000309 sponges miR-188-3p, and subsequently upregulates GPX4 expression, inactivating ferroptosis-dependent mitochondrial function and podocyte apoptosis. Suppressor Down regulation Up regulation Down regulation Driver Suppressor C57BL/6J mice were purchased from Three Gorges University (Yichang, China), and C57BL/KsJ and male db/db mice were from Changzhou Cavins Laboratory Animal Co. Ltd. (Changzhou, China). All experiments were approved by the Animal Ethics Committee of Zhejiang Provincial People's Hospital, and performed according to specific institutional and national guidelines. The mice were divided into three groups: control C57BL/6J mice, db/db mice, and germacrone-treated db/db mice (db/db + Ger) (n = 10/each group). The db/db + Ger mice received germacrone treatment at a dosage of 10 mg/kg/day, while C57BL/6J mice and db/db mice had been given the same volumes of 0.9% saline simultaneously. REF000609 ICD-11: GB61 Diabetic nephropathy CELL00564 MPC5 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique00716 Formononetin (FN) alleviates chronic kidney disease (CKD) by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD. In addition, FN also promoted the separation of the Nrf2/ Keap1 complex and enhanced Nrf2 nuclear accumulation. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium(30 mg/kg). Then, UUO surgery orsham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10% DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10% DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium (30 mg/kg). Then, UUO surgery or sham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10 % DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10 % DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. REF000929 ICD-11: GB61 Chronic kidney disease CELL10145 pTECs Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00243 Erastin and high glucose both induced ferroptosis in mesangial cells. Suppression of HMGB1 restored cellular proliferation, prevented ROS and LDH generation, decreased ACSL4, PTGS2, and NOX1, and increased GPX4 levels in mesangial cells. Furthermore, nuclear factor E2-related factor 2 (Nrf2) was decreased in diabetic nephropathy (DN) patients and high glucose-mediated translocation of HMGB1 in mesangial cells. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000317 ICD-11: GB61 Diabetic nephropathy CELL00575 SV40-MES 13 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell proliferation
unique00714 Formononetin (FN) alleviates chronic kidney disease (CKD) by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD. In addition, FN also promoted the separation of the Nrf2/Keap1 complex and enhanced Nrf2 nuclear accumulation. Suppressor Down regulation Up regulation Down regulation Driver Suppressor For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium(30 mg/kg). Then, UUO surgery orsham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10% DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10% DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium (30 mg/kg). Then, UUO surgery or sham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10 % DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10 % DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. REF000929 ICD-11: GB61 Chronic kidney disease CELL10145 pTECs Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00715 Formononetin (FN) alleviates chronic kidney disease (CKD) by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD. In addition, FN also promoted the separation of the Nrf2/Keap1 complex and enhanced Nrf2 nuclear accumulation. Suppressor Down regulation Up regulation Down regulation Driver Suppressor For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium(30 mg/kg). Then, UUO surgery orsham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10% DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10% DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium (30 mg/kg). Then, UUO surgery or sham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10 % DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10 % DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. REF000929 ICD-11: GB61 Chronic kidney disease CELL10145 pTECs Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01452 Renal dysfunction and renal tubular epithelial damage induced by Bisphenol A (BPA) are linked to ferroptosis, which depends on the activation of ferritinophagy through AMPK-mTOR- ULK1 axis. These findings revealed that after BPA treatment, FTH was significantly reduced and iron was accumulated. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor Balb/c mice aged 6-8 weeks were purchased from Liaoning Changsheng biotechnology co., Ltd. (Benxi, China). All animal experiments comply with the requirements of the Institutional Animal Care and Use Committee (IACUC) of Jilin University. The mice were housed in separate cages and given enough food and drinking water during the conditions of a 12-h light and dark cycle. The establishment of animal models is as previously described. REF000687 ICD-11: GB6Z Renal dysfunction CELL00556 TCMK-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique01189 Postoperative cognitive dysfunction (POCD) is a complication of the central nervous system (CNS) often occurred after surgery or anesthesia in the elder patients. Downregulation of MIB2 could alleviate the sevoflurane-anesthesia-induced cognitive dysfunction and neuron injury through reducing ferroptosis via GPX4. Inducer Up regulation Down regulation Down regulation Driver Suppressor Male C57BL/6 mice were obtained from Beijing HFK Bioscience Co., Ltd., China. The mice were then randomly separated into sham and sevoflurane administrated (SEV) groups, with each group containing 20 animals. In SEV groups, mice were placed in an anesthetizing chamber and exposed to 2.5% sevoflurane (CAS No. 28523-86-6, no. S2464, Selleck, Shanghai, China) with complete oxygen for 2 h, and sham group mice were conducted with the same procedure without sevoflurane exposure. REF000431 ICD-11: MB21 Postoperative cognitive dysfunction CELL10144 Primary Neuron Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00471 Tectorigenin exerts as a Smad3 inhibitor to suppress Smad3 activation through an Nox4-dependent mechanism. Tectorigenin protects against unilateral ureteral obstruction by inhibiting Smad3-mediated ferroptosis and fibrosis. Suppressor Down regulation Down regulation Up regulation Driver Driver The male C57BL/6 mice (8 weeks old, 22-25 g body weight) used in this study were purchased from Dashuo Bio-Technique Co. Ltd. (Chengdu, China) and were maintained in 12 hr of light/12 hr of darkness. The mice were randomly divided into the following 4 groups (n = 8 per group): Sham, UUO, UUO with tectorigenin (20 mg/kg/day, dissolved in saline with 10% dimethyl sulfoxide [DMSO]) or irbesartan (IRB, a positive control, 20 mg/kg/day) treatment. After anesthesia with 1% pentobarbital, the left ureter was exposed through the lower left incision on the midline of the back and blocked by two-point ligation with 40 silk thread as previously described. The Sham-operated mice underwent the same operation but absence of ligation. The tectorigenin and IRB group were administered intraperitoneally with drug daily for 7 consecutive days since surgery. Sham-operated mice and UUO mice were received the equal volume of solvent. REF000628 ICD-11: MG30 Unilateral ureteral obstruction CELL10151 Renal tubular epithelial cells Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01334 Melatonin administration reduced the level of circPtpn14 (mmu_circ_0000130), which functioned by acting as a miR-351-5p sponge to positively regulate the expression of the ferroptosis-related 5-lipoxygenase (5-LOX). In addition, melatonin alleviated longterm sleep disorders and improved neurological function in Traumatic brain injury (TBI) mice. Thus, these findings suggested that melatonin might potentially protect the injured brain by attenuating ferroptosis and ER stress. Suppressor Down regulation Down regulation Up regulation Driver Driver Male C57BL/6 mice aged 6-8 weeks were purchased from the Chongqing Medical University Animal Experiment Center (Chongqing, China). Mice were randomly allocated into three groups including sham group, TBI group, and melatonin treatment group. 30 mice were used for MRI and cerebral blood flow (CBF) monitoring at the 3rd and 7th day, with 5 in each group; 15 mice were used for EEG detection at the 14th and 30th days, training and testing inwater mazeduring the 25th-30th days, with 5 in each group. 15 mice were used for brain water content determination on the 3rd day, with 5 in each group. 9 mice were used for RNA sequencing, with 3 in each group; 75 mice were used for brain tissue acquisition, with 5 in each group with 5 time points (1st, 3rd, 7th, 14th, and 30th day after the operation). REF000604 ICD-11: NA07 Traumatic brain injury CELL00543 bEnd3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01335 Melatonin administration reduced the level of circPtpn14 (mmu_circ_0000130), which functioned by acting as a miR-351-5p sponge to positively regulate the expression of the ferroptosis-related 5-lipoxygenase (5-LOX). In addition, melatonin alleviated longterm sleep disorders and improved neurological function in Traumatic brain injury (TBI) mice. Thus, these findings suggested that melatonin might potentially protect the injured brain by attenuating ferroptosis and ER stress. Suppressor Up regulation Down regulation Down regulation Suppressor Driver Male C57BL/6 mice aged 6-8 weeks were purchased from the Chongqing Medical University Animal Experiment Center (Chongqing, China). Mice were randomly allocated into three groups including sham group, TBI group, and melatonin treatment group. 30 mice were used for MRI and cerebral blood flow (CBF) monitoring at the 3rd and 7th day, with 5 in each group; 15 mice were used for EEG detection at the 14th and 30th days, training and testing inwater mazeduring the 25th-30th days, with 5 in each group. 15 mice were used for brain water content determination on the 3rd day, with 5 in each group. 9 mice were used for RNA sequencing, with 3 in each group; 75 mice were used for brain tissue acquisition, with 5 in each group with 5 time points (1st, 3rd, 7th, 14th, and 30th day after the operation). REF000604 ICD-11: NA07 Traumatic brain injury CELL00543 bEnd3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00666 When we applied recombinant IL-17A in Sal+hyperoxia group mice, the protein levels of IL-17RA, Act1, TRAF6, p38 MAPK and p-p38 MAPK increased significantly, and the expression level of GPX4 significantly decreased. Therefore, we demonstrated that IL-17A/IL-17RA mediates ferroptosis of AECII, least in part, via Act1/TRAF6/p38 MAPK pathway, which is responsible for the protective effects of salidroside on hyperoxia-induced acute lung injury (HALI). Inducer Down regulation Down regulation Up regulation Suppressor Suppressor In our study, the 32 mice were randomly divided for four groups (n = 8 per group): (1) room-air-expose (sham), (2) hyperoxia-expose with Sal (Sal + Hyperoxia), (3) hyperoxia-exposed (Hyperoxia), (4) hyperoxia-exposed with Y-320 (an inhibitor of IL-17) (Y-320 + Hyperoxia). The mice exposed to normoxia groups were placed in room air with 21% oxygen, and the mice exposed to hyperoxia were placed in over 90% oxygen for 24 h. The continue exposure to over 90% oxygen was achieved in a self-made airtight box which attached to a medical oxygen cylinder, and the O2 level inside was continuously monitored with O2 analyzer, mice had free access to food and water. In the first three days before exposure to the hyperoxia, mice in the Sal + Hyperoxia group or Y-320 + Hyperoxia group were treated with Sal (100 mg/Kg) or Y-320 (2 mg/Kg) once orally every day, while the rest of groups were given equal isotonic saline. Based on the above experiments, eight 8-week-old KM mice were randomly divided into two groups: Sal + Hyperoxia group and Sal + Hyperoxia + IL-17A group. Sal + Hyperoxia + IL-17A group, mice were i.v. injected with 50 ug/kg of recombinant mouse IL-17A (210-17, Pepro Tech, USA). Animal were sacrificed following reperfusion, and lungs were stored at -80 until further experimental analysis. REF000893 ICD-11: NB32 Hyperoxia induced acute lung injury CELL10134 Lung tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00631 Astaxanthin protected LPS-induced cell inflammation and acute lung injury (ALI) in mice by inhibiting ferroptosis, and its effect was achieved through Keap1-Nrf2/HO-1 pathway. Therefore, our study indicates that ferroptosis will become a new target for the treatment of ALI, and astaxanthin is a potential drug for the treatment of ALI. Suppressor Down regulation Up regulation Down regulation Driver Suppressor 6-week-Babl/c female mice were randomized to the following three groups of seven mice each: vehicle group, LPS group, Astaxanthin plus LPS group. Astaxanthin plus LPS group mice were pretreated with astaxanthin (20 mg/kg) byi.v injectionfor daily for 7 consecutive days. Astaxanthin was dissolved in 2%DMSO (vol/vol), 40% PEG-400 (vol/vol), 2% Tween 80 (vol/vol), and 56% PBS (vol/vol). On the last day, the mice were intraperitoneally injected with 5 mg/kg LPS or normal saline 2 h after the injection of astaxanthin. After 6 h of LPS stimulation, mice were euthanized to collect the BALF, and lung tissue samples. BALF was collected three times through a tracheal cannula with autoclaved normal saline, instilled up to a total volume of 1.8 ml. REF000863 ICD-11: NB32 Acute lung injury CELL00553 RAW264.7 Ferroptosis (hsa04216) Cell ferroptosis
unique00630 Astaxanthin protected LPS-induced cell inflammation and acute lung injury (ALI) in mice by inhibiting ferroptosis, and its effect was achieved through Keap1-Nrf2/HO-1 pathway. Therefore, our study indicates that ferroptosis will become a new target for the treatment of ALI, and astaxanthin is a potential drug for the treatment of ALI. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor 6-week-Babl/c female mice were randomized to the following three groups of seven mice each: vehicle group, LPS group, Astaxanthin plus LPS group. Astaxanthin plus LPS group mice were pretreated with astaxanthin (20 mg/kg) byi.v injectionfor daily for 7 consecutive days. Astaxanthin was dissolved in 2%DMSO (vol/vol), 40% PEG-400 (vol/vol), 2% Tween 80 (vol/vol), and 56% PBS (vol/vol). On the last day, the mice were intraperitoneally injected with 5 mg/kg LPS or normal saline 2 h after the injection of astaxanthin. After 6 h of LPS stimulation, mice were euthanized to collect the BALF, and lung tissue samples. BALF was collected three times through a tracheal cannula with autoclaved normal saline, instilled up to a total volume of 1.8 ml. REF000863 ICD-11: NB32 Acute lung injury CELL00553 RAW264.7 Ferroptosis (hsa04216) Cell ferroptosis
unique00255 Ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and panaxydol (PX) might ameliorate LPS-induced inflammation via inhibiting ferroptosis. PX attenuates ferroptosis against LPS-induced acute lung injury via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for acute lung injury. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor Specific pathogen-free (SPF) male C57BL/6 mice (6-8 weeks old, 20-24 g body weight) were purchased from the Experimental Animal Center, Anhui Medical University (Hefei, China). All mice were randomly divided into five groups (8 mice every group): control group, LPS group, PX+LPS group (administered 20 mg/kg PX), Fe+LPS group (administered 15 mg/kg Fe-citrate (III)), and PX+Fe+LPS group (administered 20 mg/kg PX and 15 mg/kg Fe-citrate (III)). Fe-citrate (III) was dissolved in stroke-physiological saline solution (SPSS). PX was dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich), and further diluted in SPSS. Intravenous injection of Fe or/and intraperitoneal injection of PX were performed from day 0 to day 2. At 1 h after the final Fe and PX treatment, the mice were anesthetized with 30 mg/kg of pentobarbital sodium (Beijing Chemical Co., China) and then LPS (10 ug/mouse; InvivoGen, San Diego, CA, USA) or SPSS was injected into the trachea. REF000342 ICD-11: NB32 Acute lung injury CELL00076 BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Pathways in cancer (hsa05200) Cell ferroptosis
unique00342 Ulinastatin (UT1) plays a role in mitigation of Acetaminophen (APAP)-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression. Suppressor Up regulation Up regulation Up regulation Suppressor Suppressor Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection. REF000464 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL00304 LO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00178 (+)-clausenamide ((+)-CLA) specifically reacted with the Cys-151 residue of Keap1, which blocked Nrf2 ubiquitylation and resulted in an increased Nrf2 stability. Thus, (+)-CLA protects against acetaminophen-induced hepatotoxicity via inhibiting ferroptosis and activating the Keap1/Nrf2 pathway in a Cys-151-dependent manner. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor Male C57BL/6 mice aged 8-10 weeks were purchased from Guangdong Experimental Animal Center (Guangzhou, China). The animals were maintained on a 12 h light-dark cycle in a regulated temperature and humidity environment for 1 week before drug administration. (+)-CLA (50 mg/kg/day, i.g.) or fer-1 (2.5 umol/kg/day, i.p.)were administered for 7 consecutive days. To induce liver injury, mice were injected with erastin (100 mg/kg/day, i.p., twice a day) on both the 6th and 7th day, or a single dose of APAP (600 mg/kg/day, i.p.) on the 7th day after overnight food deprivation. The serum and livers were obtained for analysis. REF000236 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL00315; CELL00017; CELL00048; CELL00291 Hepa RG; SMMC-7721; HepaG2; Bel-7402 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Pathways in cancer (hsa05200) Cell ferroptosis
unique00565 Baicalin-pretreated MSCs (Ba-Exo) exerts a protective effect on liver function and activates the Keap1-NRF2 pathway via P62 (SQSTM1), thereby inhibiting ROS production and lipid peroxide-induced ferroptosis. Therefore, baicalin pretreatment is an effective and promising approach in optimizing the therapeutic efficacy of Exo in acute liver injury (ALI). Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor C57BL/6 mice at 6-8 weeks were intraperitoneally injected with D-GalN/LPS (1772-03-8/L2880, Sigma-Aldrich, USA) at a dose of 700 mg/kg and 10 ug/kg, respectively. The constructed D-GaIN/LPS-induced ALI model mice were named the model group, and the normal mice injected with phosphate-buffered saline (PBS) were named the blank group. After 1 h of LPS/D-GalN treatment, Exo and Ba-Exo (150 ug/mice) were injected into the tail vein of the mice in the Exo and Ba-Exo groups, respectively. Mice were sacrificed via anesthesia overdose 12 h after the intervention. Half of the liver tissue was fixed in paraformaldehyde, while the other half was frozen at 80 . Peripheral blood serum was stored at -80 . REF000793 ICD-11: NB91 Acute liver injury . Exosomes Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique00564 Baicalin-pretreated MSCs (Ba-Exo) exerts a protective effect on liver function and activates the Keap1-NRF2 pathway via P62 (SQSTM1), thereby inhibiting ROS production and lipid peroxide-induced ferroptosis. Therefore, baicalin pretreatment is an effective and promising approach in optimizing the therapeutic efficacy of Exo in acute liver injury (ALI). Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor C57BL/6 mice at 6-8 weeks were intraperitoneally injected with D-GalN/LPS (1772-03-8/L2880, Sigma-Aldrich, USA) at a dose of 700 mg/kg and 10 ug/kg, respectively. The constructed D-GaIN/LPS-induced ALI model mice were named the model group, and the normal mice injected with phosphate-buffered saline (PBS) were named the blank group. After 1 h of LPS/D-GalN treatment, Exo and Ba-Exo (150 ug/mice) were injected into the tail vein of the mice in the Exo and Ba-Exo groups, respectively. Mice were sacrificed via anesthesia overdose 12 h after the intervention. Half of the liver tissue was fixed in paraformaldehyde, while the other half was frozen at 80 . Peripheral blood serum was stored at -80 . REF000793 ICD-11: NB91 Acute liver injury . Exosomes Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique00340 Ulinastatin plays a role in mitigation of Acetaminophen (APAP)-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection. REF000464 ICD-11: NB91 Liver injury CELL00304 LO2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00341 Ulinastatin plays a role in mitigation of Acetaminophen (APAP)-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection. REF000464 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL00304 LO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00610 Xiaojianzhong (XJZ) significantly counteracted aspirin-induced gastric mucosal injury and inhibited oxidative stress and ferroptosis in mice. Upon examining SQSTM1/p62(p62)/ Kelch-like ECH-associated protein 1 (Keap1)/Nuclear Factor erythroid 2-Related Factor 2 (Nrf2), a well-known signaling pathway involved in the regulation of oxidative stress and ferroptosis, we found that its activation was significantly inhibited by aspirin treatment and that this signaling pathway was activated after XJZ intervention. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor C57BL/6 mice (Male, 6-8 weeks old, 20 g± 2 g) were purchased from Chengdu Yaokang Biotechnology Co., Ltd. (Chengdu, China). All animals were housed in the animal room of Shaanxi University ofTraditional Chinese Medicine, at a temperature of 22 ± 2 and a humidity of 40% ± 5%, alternating between light and dark. In the study, the mice were randomly divided into six groups (n = 10 in each group): the blank group, model group,XJZ high dose group, XJZ medium dose group, XJZ low dose group, and positive control (omeprazole) group. The mice in the model group were given Aspirin (300 mg/kg) via gavage for 14 days; the mice in the XJZ high dose group, XJZ medium dose group, and XJZ low dose group were given aspirin (300 mg/kg) by gavage in the morning and three different concentrations (12 g/kg, 6 g/kg, or 3 g/kg) of XJZ decoction by gavage in the afternoon; the mice in the positive control group were given aspirin (300 mg/kg) by gavage in the morning andomeprazole(20 mg/kg) by gavage in the afternoon. After the model was successfully constructed, the mice were anesthetized with isoflurane and gastric tissues were extracted for analysis. REF000836 ICD-11: NB91 Liver injury CELL10015 Gastric tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00369 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/ Sirt1 axis. Inducer Down regulation Up regulation Down regulation Suppressor Driver . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01256 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/Sirt1 axis. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00372 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/ Sirt1 axis. Inducer Down regulation Down regulation Up regulation Suppressor Marker/Suppressor . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01259 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/Sirt1 axis. Inducer Up regulation Down regulation Down regulation Driver Marker/Suppressor . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00373 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/ Sirt1 axis. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01260 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/Sirt1 axis. Inducer Up regulation Down regulation Down regulation Driver Suppressor . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00092 Furosine might decrease the activity of GPX4 via AR, thereby disrupting the conversion of peroxides into non-toxic reduced forms. Once GPX4 loses its reduction activity, excessivelipid peroxidationin kidney cells can lead to cell death by ferroptosis. To conclude, the study demonstrated for the first time the toxicity of furosine toward kidney injury. Inducer Up regulation Down regulation Down regulation Driver Suppressor A total of 60 ICR female mice (20 ± 2g, 5 mice/group) were divided into 12 groups (control and 10 furosine treatment groups). Furosine was dissolved in distilled water and a dose of 0.24 g/kg b.w. was administered by gavage or tail vein injection (0.2 mL volume per mouse) once at the beginning. This dose was chosen based on the median lethal dose (LD50) determined in previous acute toxicity experiments, in which the LD50 of furosine was 1.6 g/kg b.w. Mice were fasted for 4 h prior to dosing; animals were sacrificed at 0 (controls), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after administration, and kidney tissue was dissected and blood samples were collected. REF000147 ICD-11: NB92 Kidney injury CELL10143 Primary kidney cells Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00370 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/ Sirt1 axis. Inducer Down regulation Up regulation Down regulation Suppressor Driver . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01257 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/Sirt1 axis. Inducer Up regulation Up regulation Up regulation Driver Driver . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00077 Roxadustat (FG-4592) pretreatment is achieved mainly by decreasing ferroptosis at the early stage of FA-induced kidney injury via Akt/GSK-3-mediated Nrf2 activation, which retards the fibrosis progression. Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor C57BL/6 male mice, 6 to 8 weeks old, were purchased from Liaoning Changsheng Biotechnology Co. (Liaoning, China). The animal experiment was conducted in three parts. In the first part, mice were randomly divided into 4 groups (n = 12/group): (1) control group that received an intraperitoneal injection of saline, (2) FG-4592 group that received intraperitoneal injection of FG-4592 once (10 mg/kg, dissolved in DMSO at 50 mg/ml and then further diluted in sterile phosphate-buffered saline to 1 mg/ml), (3) FA group that received intraperitoneal injection of a single dose of FA (250 mg/kg, dissolved in 0.3 M sodium bicarbonate), and (4) FA + FG-4592 group that received FG-4592 two days prior to FA single-dose injection. Kidney specimens and blood samples were collected on the second day (n = 6/group) and the fourteenth day (n = 6/group) after FA injection for further examination. In the second part, mice were treated with a ferroptosis inhibitor (Fer-1). In the third part, mice were treated with a PI3K inhibitor (wortmannin). REF000133 ICD-11: NB92 FA-induced kidney injury CELL10148 Renal Tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique00371 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/ Sirt1 axis. Inducer Down regulation Up regulation Down regulation Suppressor Marker . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01258 CdCl2-initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. It is possible that the damage caused by cadmium results from the induced ferroptosis and apoptosis via the miR-34a-5p/Sirt1 axis. Inducer Up regulation Up regulation Up regulation Driver Marker . REF000507 ICD-11: NB92 CdCl2-induced renal toxicity CELL00597 PC12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00455 Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway. Inducer Up regulation Up regulation Up regulation Driver Driver Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500). REF000598 ICD-11: NB9Z Testicular injury CELL00558; CELL00559 Testicular injury; TM4 Sertoli Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); HIF-1 signaling pathway (hsa04066) Cell ferroptosis
unique00299 Lipoxin A4 (LXA4) enhanced the protein expression of p-AKT, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and haem-oxygenase-1 (HO-1) in primary spinal cord neurons. LXA4 exerted a neuroprotective effect in Erastin-induced ferroptosis of primary spinal cord neurons by activating the Akt/Nrf2/HO-1 signaling pathway. Thus, LXA4 may be a potential therapeutic agent for spinal cord injury (SCI). Suppressor Up regulation Up regulation Up regulation Suppressor Marker/Suppressor Pregnant C57BL/6 mouse was purchased from Laboratory Animal Center of Xinxiang Medical University. pregnant mouse was anesthetized with CO2 and sacrificed by cervical dislocation at embryonic day 15. All embryos were separated from pregnant mouse under aseptic conditions. Under dissection microscope, each embryo was quickly killed by cervical dislocation, and the spinal cord was isolated. The membrane of the spinal cord and dorsal root ganglion was removed from the spinal cord applying microforceps. Subsequently, the spinal cord was quickly cut into small pieces (1 mm3) using ultrafine microscissors. REF000419 ICD-11: ND51 Spinal cord injury CELL10146 Primary spinal cord neurons Fatty acid metabolism (hsa01212); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
dupunique01741 Sevoflurane could enhance 15LO2-PEBP1 interaction and activate ATM and its downstream P53/SAT1 pathway, which might be attributed to excessive p-ATM nuclear translocation, indicating a potential therapeutic target for ameliorating sevoflurane-induced neurotoxicity. Inducer Up regulation Up regulation Up regulation Driver Driver Pregnant rats were placed in a dedicated plastic chamber with ambient gas at a flow rate of 2L/min. Fer-1 solubilized in saline and 1% dimethyl sulfoxide (DMSO) and PD146176 (a specific 15LOX inhibitor) dissolved in corn oil containing 1% DMSO were administered intraperitoneally to rats at a dose of 5 mg/kg 1 h before each exposure, respectively. Similarly, 0.5 mg/kg Ku55933 (an ATM inhibitor), which is diluted in saline containing 1% DMSO, was intraperitoneally administered 2 h previously. REF000960 ICD-11: NE61 Sevoflurane induced neurotoxicity CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00789 Methamphetamine (METH) and HIV-1 lead to oxidative stress and their combined effect increases the risk of HIV-associated neurocognitive disorder (HAND), which may be related to the synergistic ferroptotic impairment in microglia. We found that METH and HIV-1 Tat reduced the expression of ferroptotic protein GPX4 and the cell viability and enhanced the expression of P53 and the level of ferrous iron, while the above indices were significantly improved with pretreatment of ferrostatin-1. Inducer . Down regulation . . Suppressor . REF001010 ICD-11: 1C60-1C62 HIV-associated neurocognitive disorder CELL00544 BV2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01781 Methamphetamine (METH) and HIV-1 lead to oxidative stress and their combined effect increases the risk of HIV-associated neurocognitive disorder (HAND), which may be related to the synergistic ferroptotic impairment in microglia. We found that METH and HIV-1 Tat reduced the expression of ferroptotic protein GPX4 and the cell viability and enhanced the expression of P53 and the level of ferrous iron, while the above indices were significantly improved with pretreatment of ferrostatin-1. Inducer Up regulation . . Driver . . REF001010 ICD-11: 1C60-1C62 HIV-associated neurocognitive disorder CELL00544 BV2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01406 NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. . . . Down regulation Driver Driver/Suppressor Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). The rats were housed under room temperatures (25 ± 2 and 12-h light/dark cycle) and given water and food ad libitum before the trial. Then, they were randomly assigned into the control group (n = 10), model group (n = 10), and model + miR-9-5p angomir group (n = 10). All animal procedures were performed under the Care and Use of Laboratory Animals guidelines and approved by the Guangdong Academy of Medical Sciences. According to a previous study, sepsis was induced by the cecal ligation and puncture (CLP) method. Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000648 ICD-11: 1G40-1G41 Sepsis CELL00543 bEnd.3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01552 Sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate sepsis-associated encephalopathy (SAE) by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis. And NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. . . . Down regulation Suppressor Driver/Suppressor Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000763 ICD-11: 1G40-1G41 Sepsis-associated encephalopathy CELL00543 bEnd.3 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01404 NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. . . . Up regulation Suppressor Driver/Suppressor Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). The rats were housed under room temperatures (25 ± 2 and 12-h light/dark cycle) and given water and food ad libitum before the trial. Then, they were randomly assigned into the control group (n = 10), model group (n = 10), and model + miR-9-5p angomir group (n = 10). All animal procedures were performed under the Care and Use of Laboratory Animals guidelines and approved by the Guangdong Academy of Medical Sciences. According to a previous study, sepsis was induced by the cecal ligation and puncture (CLP) method. Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000648 ICD-11: 1G40-1G41 Sepsis CELL00543 bEnd.3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01551 Sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate sepsis-associated encephalopathy (SAE) by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis. And NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. . . . Up regulation Driver Driver/Suppressor Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000763 ICD-11: 1G40-1G41 Sepsis-associated encephalopathy CELL00543 bEnd.3 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00625 In both animal and cell studies, Acetaminophen reduced iron content, ROS, glutamate antiporter (xCT), 4-hydroxy-2-nonenal (4-HNE) levels but increased GPX4 expression. Our findings suggest that APAP reduces sepsis-induced cognitive impairment by reducing ferroptosis, which is mediated by the GPX4 signaling pathway. Suppressor . Up regulation . . Suppressor Healthy male C57BL/6J mice, weighing 22-24 g, 6 weeks old, were purchased from Tianyao Biotechnology Company (Tianjin, China) and housed in an environment free of specific pathogenic bacteria: temperature 22-24 , relative humidity 50%-70%, alternating day and night every 12 h, and free access to water. The cecal ligation and puncture (CLP) approach was used to establish septic mouse models. The survival rates for 7 days were determined. The Morris water maze (MWM) was utilized to assess cognitive function. Hematoxylin and eosin (HE) staining identified histopathologic alterations in hippocampal tissue. REF000855 ICD-11: 1G40-1G41 Sepsis-associated encephalopathy CELL10017; CELL00549 Hippocampal tissue; HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00665 In conclusion, irisin could ameliorate inflammatory microenvironment in Sepsis-associated encephalopathy by suppressing hippocampus ferroptosis via the Nrf2/GPX4 signaling pathway. Suppressor . Up regulation . . Suppressor Eight-week-old wild-type (WT) and Nrf2-knockout (Nrf2-/-) littermate male mice on a C57BL/6J background were purchased from Cyagen (Suzhou, China.) and maintained at the Centre for Animals of Wuhan University (Wuhan, China). Before the experiment, the mice were separated and given light and dark cycles for 12 h, 22 ± 0.5 temperature, 60 ± 10% humidity, and free accessed to food and water for at least 1 week. Mice were randomly distributed into sham, CLP, CLP + Irisin (Ir group) and CLP + Irisin + Era (Ir + Era group) groups. REF000892 ICD-11: 1G40-1G41 Sepsis-associated encephalopathy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00115 The attenuation of sepsisinduced HO1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dexmedetomidine alleviates sepsis induced myocardial cellular injury. Suppressor . Up regulation . . Suppressor A total of 32 male C57BL/6 mice (25 g, 8 weeks old) were obtained from the Guangdong Medical Lab Animal Center and housed in the Laboratory Animal Service Center (Jinan University, Guangdong, China). Mice were anesthetized with isoflurane (RWD Life Science) inhalation at the concentration of 2.5% for anesthetic induction and then at 1% for anesthetic maintenance until the end of the CLP. During the experiment, the body temperature was kept at 36-38 with a heating pad. Anesthetized mice were subjected to midline laparotomy. The cecum was carefully separated to avoid blood vessels damage and the cecum was identified and punctured twice with a 22-gauge needle. Then, the abdominal cavity was closed with two epithelium layers, followed by a normal saline injection subcutaneously for resuscitation before mice were returned to the cage. REF000171 ICD-11: 1G40-1G41 Sepsis CELL10161 Ventricular tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00675 Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment. Suppressor . Up regulation . . Suppressor Briefly, female BALB/c mice (6-8 weeks, weighing 20-25 g, purchased from Hunan SJA Laboratory Animal Co., Ltd., Changsha, Hunan, China) were raised in specific pathogen-free conditions under controlled temperature (23-25 ) and humidity (40-80%) as well as a 12 h dark/light cycle for 1 week of acclimation. They were fed a standard chow diet and waterad libitum. Mice were anaesthetised with 2% isoflurane inhalation and underwent moderate caecal ligation and puncture in accordance with a previously reported protocol (Rittirsch etal.2009). Meanwhile, mice in the control groups were subjected to a sham operation. Buprenorphin (0.05 mg/kg) was injected for postoperative analgesia, and all mice were placed in cages immediately after the surgical procedures with free access to water and food (Rittirsch etal. 2009). REF000898 ICD-11: 1G40-1G41 Sepsis CELL00557 MLE-12 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00116 The attenuation of sepsisinduced HO1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dexmedetomidine alleviates sepsis induced myocardial cellular injury. Suppressor . Up regulation . . Driver/Suppressor A total of 32 male C57BL/6 mice (25 g, 8 weeks old) were obtained from the Guangdong Medical Lab Animal Center and housed in the Laboratory Animal Service Center (Jinan University, Guangdong, China). Mice were anesthetized with isoflurane (RWD Life Science) inhalation at the concentration of 2.5% for anesthetic induction and then at 1% for anesthetic maintenance until the end of the CLP. During the experiment, the body temperature was kept at 36-38 with a heating pad. Anesthetized mice were subjected to midline laparotomy. The cecum was carefully separated to avoid blood vessels damage and the cecum was identified and punctured twice with a 22-gauge needle. Then, the abdominal cavity was closed with two epithelium layers, followed by a normal saline injection subcutaneously for resuscitation before mice were returned to the cage. REF000171 ICD-11: 1G40-1G41 Sepsis CELL10161 Ventricular tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01598 The mmu-miR-7212-5p-Hmox1 axis in ferroptosis and m6A RNA methylation regulators may have potential clinical significance for the future treatment of Sepsis-associated acute kidney injury (SA-AKI). . . . Down regulation Driver Suppressor C57BL/6 mice (male, 6-8 weeks old) were purchased from Guangdong Yaokang Biotechnology Co., Ltd. (China). According to a common sepsis protocol, we used the cecal ligation and puncture (CLP) method to construct a model of sepsis. For RNA sequencing, 5 mice were randomly divided into 2 groups: the CLP group (n = 3) and the sham group (n = 2). We anesthetized mice in the CLP group with 24% isoflurane. Under aseptic conditions, a 2-cm midline laparotomy was created below the diaphragm to expose the cecum. Two-thirds of the cecum was ligated with a 5-0 silk suture and punctured twice using a 22-gauge needle. The cecum was gently squeezed to extrude a small amount of feces through the perforation site. Animals were resuscitated with 1 mL of subcutaneous saline after CLP. The procedures of the sham group (controls) were the same as the CLP group, except for the ligation and perforation. The mice were sacrificed via neck fracture 6 hours after CLP, and the kidneys were taken for subsequent RNA sequencing. REF000804 ICD-11: 1G40 Sepsis-associated acute kidney injury CELL00556 TCMK-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01451 MiR-124-3p can regulate LPCAT3 expression and affect lipid metabolism, which leads to ferroptosis. These results could provide the scientific basis for early diagnosis and renal replacement therapy in sepsis-associated acute renal injury. . . . Down regulation Suppressor Driver . REF000686 ICD-11: 1G40 Sepsis-associated acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00674 Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment. Suppressor . Up regulation . . Marker/Suppressor Briefly, female BALB/c mice (6-8 weeks, weighing 20-25 g, purchased from Hunan SJA Laboratory Animal Co., Ltd., Changsha, Hunan, China) were raised in specific pathogen-free conditions under controlled temperature (23-25 ) and humidity (40-80%) as well as a 12 h dark/light cycle for 1 week of acclimation. They were fed a standard chow diet and waterad libitum. Mice were anaesthetised with 2% isoflurane inhalation and underwent moderate caecal ligation and puncture in accordance with a previously reported protocol (Rittirsch etal.2009). Meanwhile, mice in the control groups were subjected to a sham operation. Buprenorphin (0.05 mg/kg) was injected for postoperative analgesia, and all mice were placed in cages immediately after the surgical procedures with free access to water and food (Rittirsch etal. 2009). REF000898 ICD-11: 1G40-1G41 Sepsis CELL00557 MLE-12 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00664 In conclusion, irisin could ameliorate inflammatory microenvironment in sepsis-associated encephalopathy by suppressing hippocampus ferroptosis via the Nrf2/GPX4 signaling pathway. Suppressor . Up regulation . . Marker/Suppressor Eight-week-old wild-type (WT) and Nrf2-knockout (Nrf2-/-) littermate male mice on a C57BL/6J background were purchased from Cyagen (Suzhou, China.) and maintained at the Centre for Animals of Wuhan University (Wuhan, China). Before the experiment, the mice were separated and given light and dark cycles for 12 h, 22 ± 0.5 temperature, 60 ± 10% humidity, and free accessed to food and water for at least 1 week. Mice were randomly distributed into sham, CLP, CLP + Irisin (Ir group) and CLP + Irisin + Era (Ir + Era group) groups. REF000892 ICD-11: 1G40-1G41 Sepsis-associated encephalopathy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00470 MCTR1 effectively alleviates sepsis-associated acute kidney injury, at least in part, by inhibiting ferroptosis. Mechanistically, MCTR1 activates the Nrf2, which may contribute to the inhibition of ferroptosis. Suppressor . Up regulation . . Marker/Suppressor Male C57BL/6 mice aged 8-12 weeks, weighing about 25 g, were purchased from Shanghai Experimental Animal Center of China. The mice were anesthetized with isoflurane. The abdomen area was disinfected after shaving. A 1 cm midline incision was made on the lower abdomen skin to expose the cecum. A 5-0 silk thread was used to ligate the midpoint between the distal pole and the bottom of the cecum. A 21 g needle was used to penetrate the cecum twice from the mesenteric toward the antimesenteric direction. After the wound was sutured, 0.25% ropivacaine was injected subcutaneously for postoperative analgesia. The mice were immediately resuscitated by injecting prewarmed normal saline 1 ml subcutaneously. REF000627 ICD-11: 1G40 Sepsis-associated acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01405 NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. . . . Down regulation Driver Marker/Suppressor/Driver Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). The rats were housed under room temperatures (25 ± 2 and 12-h light/dark cycle) and given water and food ad libitum before the trial. Then, they were randomly assigned into the control group (n = 10), model group (n = 10), and model + miR-9-5p angomir group (n = 10). All animal procedures were performed under the Care and Use of Laboratory Animals guidelines and approved by the Guangdong Academy of Medical Sciences. According to a previous study, sepsis was induced by the cecal ligation and puncture (CLP) method. Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000648 ICD-11: 1G40-1G41 Sepsis CELL00543 bEnd.3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01550 Sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate sepsis-associated encephalopathy (SAE) by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis. And NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. . . . Down regulation Suppressor Marker/Suppressor/Driver Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000763 ICD-11: 1G40-1G41 Sepsis-associated encephalopathy CELL00543 bEnd.3 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01403 NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. . . . Up regulation Suppressor Marker/Suppressor/Driver Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). The rats were housed under room temperatures (25 ± 2 and 12-h light/dark cycle) and given water and food ad libitum before the trial. Then, they were randomly assigned into the control group (n = 10), model group (n = 10), and model + miR-9-5p angomir group (n = 10). All animal procedures were performed under the Care and Use of Laboratory Animals guidelines and approved by the Guangdong Academy of Medical Sciences. According to a previous study, sepsis was induced by the cecal ligation and puncture (CLP) method. Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000648 ICD-11: 1G40-1G41 Sepsis CELL00543 bEnd.3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01549 Sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate sepsis-associated encephalopathy (SAE) by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis. And NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. . . . Up regulation Driver Marker/Suppressor/Driver Thirty specific-pathogen-free (SPF) male C57BL/6 rats at 8 weeks weighing 200-250 g were obtained from the Experimental Animal Center of Sun Yat-sen University (Guangzhou, China). Briefly, we anesthetized the rats with 5% chloral hydrate (0.6 ml/100 g body weight) and made a 1.5 cm midline incision on the anterior abdomen to expose the cecum. Then, the cecum was ligated at 30%, punctured twice with a No.4 surgical needle to extrude the fecal content. Finally, 1 ml of normal saline was used for resuscitation. The rats in miR-9-5p angomir group were injected with 100 ng/ul miR-9-5p angomir (RiboBio, Guangzhou, China) into caudal vein (model + miR-9-5p angomir). The rats in the control group experienced the same procedure without ligation and puncture. REF000763 ICD-11: 1G40-1G41 Sepsis-associated encephalopathy CELL00543 bEnd.3 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01521 Resveratrol inhibited ferroptosis by upregulating miR-149 and downregulating HMGB1, thus improving endotoxemia-induced myocardial injury in mice. Suppressor Down regulation . . Driver . Clean male C57BL/6 mice (8-10 wk old, weighing 25-29 g) were purchased from Beijing HFK Bioscience Co. Ltd. The 90 mice were randomly assigned into nine groups after 1 wk of adaptive feeding with 10 mice in each group: normal group (intraperitoneally injected with the same amount of PBS), LPS group [intraperitoneally injected with 15 mg/kg LPS (Sigma-Aldrich, St. Louis, Cat. No. L2880)], LPS + Rsv group (intraperitoneally injected with 15 mg/kg LPS and pretreated with 50 mg/kg resveratrol; 30), LPS + antagomiR-NC group [intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL antagomiR-NC group (Merck, Darmstadt, Germany)], LPS + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Rsv + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1), and LPS + Rsv + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1. REF000736 ICD-11: 1G40 Sepsis CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique01520 Resveratrol inhibited ferroptosis by upregulating miR-149 and downregulating HMGB1, thus improving endotoxemia-induced myocardial injury in mice. Suppressor Up regulation . . Suppressor . Clean male C57BL/6 mice (8-10 wk old, weighing 25-29 g) were purchased from Beijing HFK Bioscience Co. Ltd. The 90 mice were randomly assigned into nine groups after 1 wk of adaptive feeding with 10 mice in each group: normal group (intraperitoneally injected with the same amount of PBS), LPS group [intraperitoneally injected with 15 mg/kg LPS (Sigma-Aldrich, St. Louis, Cat. No. L2880)], LPS + Rsv group (intraperitoneally injected with 15 mg/kg LPS and pretreated with 50 mg/kg resveratrol; 30), LPS + antagomiR-NC group [intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL antagomiR-NC group (Merck, Darmstadt, Germany)], LPS + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Rsv + miR-149 antagomiR group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 0.4 pmol/uL miR-149 antagomiR), LPS + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1), and LPS + Rsv + Fer-1 group (intraperitoneally injected with 15 mg/kg LPS, pretreated with 50 mg/kg resveratrol, and simultaneously injected with 2.5 umol/kg ferroptosis inhibitor ferrostatin-1. REF000736 ICD-11: 1G40 Sepsis CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00169 Dihydrotanshinone I (DHI) inhibited the proliferation of human glioma cells. Following treatment of the U251 and U87 cells with DHI, changes in the expression levels of ferroptosis-associated proteins were observed; the expression level of GPX4 decreased and that of ACSL-4 increased. DHI also increased the levels of LDH and MDA in the human glioma cells and reduced the GSH/GSSG ratio. Inducer . Up regulation . . Driver . REF000224 ICD-11: 2A00 Glioma CELL10068; CELL00295; CELL00043 HEB; U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01209 miR-670-3p level was elevated in human glioblastoma, but decreased upon ferroptotic stimulation. Mechanistically, ACSL4 was required for the regulation on ferroptosis and growth of glioblastoma cells by miR-670-3p. Moreover, U87MG and A172 cells treated with miR-670-3p inhibitor showed an increased chemosensitivity to TMZ. . . . Down regulation Suppressor Driver . REF000466 ICD-11: 2A00 Glioblastoma CELL00323; CELL00068; CELL00272; CELL10031 U87MG; A172; SVGp12; HA1800 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01087 MiR-18a/ALOXE3 axis exerts tumor promoting functions by regulating ferroptosis and migration of glioblastoma cells. Mechanistically, miR-18a directly targeted ALOXE3 and suppressed its expression and functions in GBM cells. . . . Down regulation Suppressor Driver The 8-week-old male nude mice were randomly divided into two groups (6 mice per group). The investigators were not blinded to the experimental groups. Orthotopic implantation of GBM cells into the hippocampus of nude mice was performed as we previously described (n = 6). Mice were intraperitoneally injected with luciferin (150 mg/kg; catalog #P1043; Promega) and subjected to IVIS Spectrum in vivo imaging system (PerkinElmer) to determine the intracranial tumor size. REF000322 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique00081 Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma. Inducer . Up regulation . . Driver 1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively. REF000134 ICD-11: 2A00 Glioma CELL00043; CELL00243 U251; U373 mTOR signaling pathway (hsa04150); Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique01674 CircLRFN5 can be used as a potential Glioblastoma biomarker and become a target for molecular therapies or ferroptosis-dependent therapy in GBM. Mechanistically, circLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression in GSCs, which is a ferroptosis suppressor via generating the antioxidant tetrahydrobiopterin (BH4). . . . Up regulation Suppressor Suppressor Five-week-old female BALB/c nude mice were purchased from Shanghai Jihui Laboratory Animal Care Co., Ltd (Shanghai, China). All mice were bred in the Laboratory Animal Center of Shanghai Tenth Peoples Hospital under specific pathogen-free conditions. The animal experiments were performed by the Animal Care Committee of Shanghai Tenth Peoples Hospital. Briefly, each group contains five mice, and 5 x 104 GSCs were injected orthotopically into the mouse brain at 2 mm lateral and 2 mm anterior to the bregma with a stereotaxic apparatus. Then the survival time of each mouse was calculated, and the tumor volume was calculated according to the formula: V = (D x d2) / 2, where D represents the longest diameter and d represents the shortest diameter. REF000884 ICD-11: 2A00 Glioblastoma CELL10187; CELL10188; CELL10189; CELL10190; CELL10191; CELL10192 WHO grade IV specimens (GSC51, GSC52, GSC53, GSC55, GSC56 and GSC58) Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01673 CircLRFN5 can be used as a potential Glioblastoma biomarker and become a target for molecular therapies or ferroptosis-dependent therapy in GBM. Mechanistically, circLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression in GSCs, which is a ferroptosis suppressor via generating the antioxidant tetrahydrobiopterin (BH4). . . . Down regulation Driver Suppressor Five-week-old female BALB/c nude mice were purchased from Shanghai Jihui Laboratory Animal Care Co., Ltd (Shanghai, China). All mice were bred in the Laboratory Animal Center of Shanghai Tenth Peoples Hospital under specific pathogen-free conditions. The animal experiments were performed by the Animal Care Committee of Shanghai Tenth Peoples Hospital. Briefly, each group contains five mice, and 5 x 104 GSCs were injected orthotopically into the mouse brain at 2 mm lateral and 2 mm anterior to the bregma with a stereotaxic apparatus. Then the survival time of each mouse was calculated, and the tumor volume was calculated according to the formula: V = (D x d2) / 2, where D represents the longest diameter and d represents the shortest diameter. REF000884 ICD-11: 2A00 Glioblastoma CELL10187; CELL10188; CELL10189; CELL10190; CELL10191; CELL10192 WHO grade IV specimens (GSC51, GSC52, GSC53, GSC55, GSC56 and GSC58) Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01501 Rescue experiments indicated that ATXN8OS modulated TMZ-resistance of glioma through GLS2. In conclusion, ATXN8OS mediated ferroptosis and regulated the TMZ-resistance of glioma via ADAR/GLS2 pathway. . . . Up regulation Driver Driver Nude mice (four-week-old, female, 3/group) were purchased from Model Animal Research Center of Nanjing University. 2.5 x 105 luciferase labeled pcDNA3.1-ATXN8OS/GLS2 were transfected into U251 cells. After 48 h, transfected cells were injected stereotactically into thebrainof nude mice. In the first week after operation, TMZ was given to treat nude mice by oral gavage (66 mg/kg per day for 5 days), with vehicle as control. Bioluminescence imaging (IVIS Spectrum; PerkinElmer, USA) was applied for confirming the formation of intracranial tumor. 28 days late, all the mice were sacrificed. The resected tumors were measure at Lipid ROS and intracellular iron level. The whole experiments were approved by ethic committee of Shanxi Provincial Peoples Hospital. REF000723 ICD-11: 2A00 Glioma CELL00235; CELL00043 U251TR; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique01500 Rescue experiments indicated that ATXN8OS modulated TMZ-resistance of glioma through GLS2. In conclusion, ATXN8OS mediated ferroptosis and regulated the TMZ-resistance of glioma via ADAR/GLS2 pathway. . . . Up regulation Driver Driver Nude mice (four-week-old, female, 3/group) were purchased from Model Animal Research Center of Nanjing University. 2.5 x 105 luciferase labeled pcDNA3.1-ATXN8OS/GLS2 were transfected into U251 cells. After 48 h, transfected cells were injected stereotactically into thebrainof nude mice. In the first week after operation, TMZ was given to treat nude mice by oral gavage (66 mg/kg per day for 5 days), with vehicle as control. Bioluminescence imaging (IVIS Spectrum; PerkinElmer, USA) was applied for confirming the formation of intracranial tumor. 28 days late, all the mice were sacrificed. The resected tumors were measure at Lipid ROS and intracellular iron level. The whole experiments were approved by ethic committee of Shanxi Provincial Peoples Hospital. REF000723 ICD-11: 2A00 Glioma CELL00235; CELL00043 U251TR; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique00157 Sodium selenite (SS) down-regulates ferroptosis regulators; solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPx4), while it up-regulates iron accumulation and lipid peroxidation (LPO) in Glioblastoma. Inducer . Down regulation . . Suppressor . REF000211 ICD-11: 2A00 Glioblastoma CELL00323; CELL00049; CELL00002; CELL00051; CELL00096; CELL00272; CELL00068; CELL00095; CELL00087 U87MG; HeLa; MCF-7; PC3; HT-29; SVG P12; A172; HT-1080; HCT-116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00477 NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11. Inducer . Down regulation . . Suppressor Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 106 U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm3, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks. REF000635 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 NF-kappa B signaling pathway (hsa04064); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00125 Dihydroartemisinin (DHA) had a selective killing effect on glioblastoma, which was associated with over-expression of transferrin receptors. The primary mechanism by which DHA caused ferroptosis was down-regulation of GPX4 and the following lipid ROS accumulation. Inducer . Down regulation . . Suppressor . REF000179 ICD-11: 2A00 Glioblastoma CELL00295; CELL00068 U87; A172 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01632 Dihydroartemisinin could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma. Inducer . Down regulation . . Suppressor All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days. REF000843 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique00168 Dihydrotanshinone I (DHI) inhibited the proliferation of human glioma cells. Following treatment of the U251 and U87 cells with DHI, changes in the expression levels of ferroptosis-associated proteins were observed; the expression level of GPX4 decreased and that of ACSL-4 increased. DHI also increased the levels of LDH and MDA in the human glioma cells and reduced the GSH/GSSG ratio. Inducer . Down regulation . . Suppressor . REF000224 ICD-11: 2A00 Glioma CELL10068; CELL00295; CELL00043 HEB; U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01631 Dihydroartemisinin could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma. Inducer . Up regulation . . Driver All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days. REF000843 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Ferroptosis (hsa04216) Cell ferroptosis
unique00051 Lapatinib and siramesine was the most effective tyrosine kinase inhibitor and lysosome disruptor drug combination in inducing synergistic cell death in A549 and U87 cells. This cell death was through ferroptosis mediated by ROS and reduced expression of HO-1 in glioma cells. Inducer . Down regulation . . Driver/Suppressor . REF000101 ICD-11: 2A00 Glioma CELL00295; CELL00045 U87; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00052 Lapatinib and siramesine was the most effective tyrosine kinase inhibitor and lysosome disruptor drug combination in inducing synergistic cell death in A549 and U87 cells. This cell death was through ferroptosis mediated by ROS and reduced expression of HO-1 in glioma cells. Inducer . Down regulation . . Driver/Suppressor . REF000101 ICD-11: 2A00 Glioma CELL00295; CELL00045 U87; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01074 COPZ1 knockdown also led to the increase in nuclear receptor coactivator 4 (NCOA4), resulting in the degradation of ferritin, and a subsequent increase in the intracellular levels of ferrous iron and ultimately ferroptosis.The COPZ1/NCOA4/FTH1 axis is therefore a novel therapeutic target for the treatment of human glioblastoma. . . . Down regulation Suppressor Driver Mice were divided into two groups (10 mice per group) and anesthetized with an intraperitoneal injection (80 uL) containing ketamine HCl (25 mg/mL), xylazine (2.5 mg/mL), and 14.25% ethyl alcohol (diluted 1:3 in 0.9% NaCl). U87MG-NC and U87MG-sh-COPZ1#1 glioma cells (106 cells diluted in 10 uL PBS per animal) were injected into the right frontal lobes of each mouse using the following coordinates: 1 mm anterior and 2.5 mm lateral to the bregma, at a depth of 2 mm. REF000301 ICD-11: 2A00 Glioblastoma CELL00323; CELL00043; CELL00068; CELL00107; CELL00506 U87MG; U251; A172; LN229; T98 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00015 Pseudolaric acid B (PAB) improved intracellular iron by upregulation of transferrin receptor. The increased iron activated Nox4, which resulted in overproduction of H2O2and lipid peroxides. Moreover, PAB depleted intracellular GSH via p53-mediated xCT pathway, which further exacerbated accumulation of H2O2and lipid peroxides. Thus, PAB triggers ferroptosis in glioma cells and is a potential medicine for glioma treatment. Inducer . Up regulation . . Driver Twenty athymic BALB/c nude mice (aged 4 weeks, weight 20-22 g, from Shanghai laboratory animal Center, Shanghai, China) were housed in a specific pathogen-free environment. A total of 1 x 106 logarithmically growing C6 cells in 100 uL of PBS were subcutaneously injected into the right flank of each mouse. Therapeutic experiments were started when the tumor reached about 150 mm3 after about 7 days. The mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 5/group), PAB at the dosage of 10 mg/kg body weight (n = 10/group) and 20 mg/kg body weight (n = 10/group) in the same volume 50 uL once a days for 8 times. REF000040 ICD-11: 2A00 Glioma CELL00044; CELL00043; CELL00610 SHG-44;U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00045 Ibuprofen could induce ferroptosis of glioblastoma cells via downregulation of Nrf2 signaling pathway and is a potential drug for glioma treatment. All the data suggested that Nrf2 could regulate the expression of GPX4 and SLC7A11 in glioma cells. Inducer . Down regulation . . Marker/Suppressor In the intracranial glioma model, U87MG cells (5 x 105) were intracerebrally injected into the left side (bregma: 1 mm; lateral: 2 mm; ventral: 3 mm) of the brains of nude mice. Two weeks after tumor cell transplantation, mouse brains were scanned to detect tumor formation using a 3.0-T scanner (GE Signa HD MRI Systems). Then, mice were divided randomly into two groups (n = 6/group) and treated with vehicle control (PBS), oribuprofen (20 mg/kg), in 100 ul of PBS given i.p. 1x/day, 5 days/week. REF000089 ICD-11: 2A00 Glioma CELL00323; CELL00043 U87MG; U251MG Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01494 LINC01564 promotes the temozolomide (TMZ) resistance of glioma cells by upregulating NFE2L2 expression to inhibit ferroptosis. LINC01564 promotes MAPK8 mRNA stability by recruiting SRSF1, and MAPK8 was positively correlated with NFE2L2 and its targets, proving its mediation of NFE2L2. . . . Up regulation Suppressor Marker/Suppressor BALB/c nude mice (female, four-week-old) were purchased from the Nanjing Medical University Experimental Animal Department. Female mice were randomly divided into test group and control group. 2.5 x 105 LN229/TMZ cells transfected with sh-MAPK8-1 or sh-LINC01564-1 were injected into the brain of mice in test group, taking the mice injected with sh-NC-transfected ones as control. Seven days later, the mice were treated with TMZ (66 mg/kg per day, 5 days/cycle, 4 cycles in total) as a monotherapy. Tumor volume was monitored every three days in the period of TMZ treatment. The mice were killed 28 days after the injection. Tumors were excised from mice for observation and weighing as well as the detection of the level of ROS, iron (Fe2+) and proteins (i.e., NFE2L2, NQO1, FTH1 and HO-1). REF000717 ICD-11: 2A00 Glioma CELL00107; CELL00043; CELL10042 LN229; U251; NHAs Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01493 LINC01564 promotes the temozolomide (TMZ) resistance of glioma cells by upregulating NFE2L2 expression to inhibit ferroptosis. LINC01564 promotes MAPK8 mRNA stability by recruiting SRSF1, and MAPK8 was positively correlated with NFE2L2 and its targets, proving its mediation of NFE2L2. . . . Up regulation Suppressor Marker/Suppressor BALB/c nude mice (female, four-week-old) were purchased from the Nanjing Medical University Experimental Animal Department. Female mice were randomly divided into test group and control group. 2.5 x 105 LN229/TMZ cells transfected with sh-MAPK8-1 or sh-LINC01564-1 were injected into the brain of mice in test group, taking the mice injected with sh-NC-transfected ones as control. Seven days later, the mice were treated with TMZ (66 mg/kg per day, 5 days/cycle, 4 cycles in total) as a monotherapy. Tumor volume was monitored every three days in the period of TMZ treatment. The mice were killed 28 days after the injection. Tumors were excised from mice for observation and weighing as well as the detection of the level of ROS, iron (Fe2+) and proteins (i.e., NFE2L2, NQO1, FTH1 and HO-1). REF000717 ICD-11: 2A00 Glioma CELL00107; CELL00043; CELL10042 LN229; U251; NHAs Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01492 LINC01564 promotes the temozolomide (TMZ) resistance of glioma cells by upregulating NFE2L2 expression to inhibit ferroptosis. LINC01564 promotes MAPK8 mRNA stability by recruiting SRSF1, and MAPK8 was positively correlated with NFE2L2 and its targets, proving its mediation of NFE2L2. . . . Up regulation Suppressor Marker/Suppressor BALB/c nude mice (female, four-week-old) were purchased from the Nanjing Medical University Experimental Animal Department. Female mice were randomly divided into test group and control group. 2.5 x 105 LN229/TMZ cells transfected with sh-MAPK8-1 or sh-LINC01564-1 were injected into the brain of mice in test group, taking the mice injected with sh-NC-transfected ones as control. Seven days later, the mice were treated with TMZ (66 mg/kg per day, 5 days/cycle, 4 cycles in total) as a monotherapy. Tumor volume was monitored every three days in the period of TMZ treatment. The mice were killed 28 days after the injection. Tumors were excised from mice for observation and weighing as well as the detection of the level of ROS, iron (Fe2+) and proteins (i.e., NFE2L2, NQO1, FTH1 and HO-1). REF000717 ICD-11: 2A00 Glioma CELL00107; CELL00043; CELL10042 LN229; U251; NHAs Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00359 Temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells. The results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Inducer . Up regulation . . Driver . REF000487 ICD-11: 2A00 Glioblastoma CELL10069 TG905 Ferroptosis (hsa04216) Cell ferroptosis
unique01833 Amplifying IRP1 signals can reverse TMZ resistance and suppress tumor growthin vivovia inhibiting NFKB2 in the noncanonical NF-kB signaling pathway. In addition, NFKB2 affected TMZ sensitivity of glioblastoma by modulating the expression of LCN2 and FPN1. . . . Up regulation Suppressor Marker/Suppressor Four-to five-week-old female BALB/c nude mice were obtained from the Laboratory Animal Center, Southern Medical University. To study the role of IRP1 in TMZ resistance, the mice were randomly divided into four groups (n = 6 per group) (U87TR, U87TR + TMZ, U87TR-lvIRP1, U87TR-lvIRP1 + TMZ). To establish the GBM models, IRP1 overexpress or control U87TR cells (5 x 105 cells per mice in 3 uL PBS) transfected with luciferase lentivirus were injected into the mice brain under the guidance of a stereotactic instrument at coordinates relative to bregma: 2.0 mm posterior, 2.0 mm lateral, and 3.0 mm ventral. REF001054 ICD-11: 2A00 Glioblastoma CELL00579; CELL00578; CELL00506; CELL00295; CELL00043; CELL00107; CELL00068; CELL00351 N9; N33; NHA; T98; U87; U251; LN229; A172; U118 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique01593 miR-147a targets SLC40A1 to induce ferroptosis in human glioblastoma in vitro. Mechanistically, miR-147a directly bound to the 3'-untranslated region of SLC40A1 and inhibited SLC40A1-mediated iron export, thereby facilitating iron overload, lipid peroxidation, and ferroptosis. . . . Down regulation Driver Marker/Suppressor . REF000801 ICD-11: 2A00 Glioblastoma CELL00323; CELL00068; CELL10031; CELL00272 U87MG; A172; HA1800; SVGp12 Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique01391 CircCDK14 promotes the migration, invasion and proliferation of glioma cells in vitroas well as tumorigenesisin vivo. An evaluation of the underlying mechanism revealed that circCDK14 sponged miR-3938 to upregulate oncogenic gene PDGFRA expression. After knockdown of circCDK14 in glioma cells, protein levels of SLC7A11 and GPX4 decreased significantly and Fp became more sensitivity. . . . Up regulation Suppressor Suppressor 4-week-old female BALB/c nude mice were acquired from the National Laboratory Animal Center (Shanghai, China). Overall, 10 mice (n = 5 each group) were implanted with U251 cells stably knockdown circCDK14 by lentiviruses carrying sh-circCDK14 (Wanleibio, China), or control U251 cells with lentiviruses carrying sh-NC (Wanleibio, China). 5 x 106 cells were resuspended in phosphatebuffered saline (100 ul) and Matrigel substrate (100 ul) and injected into the right flank of nude mice. Tumor volume was documented once 7 days after implantation. REF000639 ICD-11: 2A00 Glioma CELL10068; CELL00392; CELL00295; CELL00043 HEB; SF126; U87; U251 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01389 CircCDK14 promotes the migration, invasion and proliferation of glioma cells in vitroas well as tumorigenesisin vivo. An evaluation of the underlying mechanism revealed that circCDK14 sponged miR-3938 to upregulate oncogenic gene PDGFRA expression. After knockdown of circCDK14 in glioma cells, protein levels of SLC7A11 and GPX4 decreased significantly and Fp became more sensitivity. . . . Down regulation Driver Suppressor 4-week-old female BALB/c nude mice were acquired from the National Laboratory Animal Center (Shanghai, China). Overall, 10 mice (n = 5 each group) were implanted with U251 cells stably knockdown circCDK14 by lentiviruses carrying sh-circCDK14 (Wanleibio, China), or control U251 cells with lentiviruses carrying sh-NC (Wanleibio, China). 5 x 106 cells were resuspended in phosphatebuffered saline (100 ul) and Matrigel substrate (100 ul) and injected into the right flank of nude mice. Tumor volume was documented once 7 days after implantation. REF000639 ICD-11: 2A00 Glioma CELL10068; CELL00392; CELL00295; CELL00043 HEB; SF126; U87; U251 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01390 CircCDK14 promotes the migration, invasion and proliferation of glioma cells in vitroas well as tumorigenesisin vivo. An evaluation of the underlying mechanism revealed that circCDK14 sponged miR-3938 to upregulate oncogenic gene PDGFRA expression. After knockdown of circCDK14 in glioma cells, protein levels of SLC7A11 and GPX4 decreased significantly and Fp became more sensitivity. . . . Up regulation Suppressor Suppressor 4-week-old female BALB/c nude mice were acquired from the National Laboratory Animal Center (Shanghai, China). Overall, 10 mice (n = 5 each group) were implanted with U251 cells stably knockdown circCDK14 by lentiviruses carrying sh-circCDK14 (Wanleibio, China), or control U251 cells with lentiviruses carrying sh-NC (Wanleibio, China). 5 x 106 cells were resuspended in phosphatebuffered saline (100 ul) and Matrigel substrate (100 ul) and injected into the right flank of nude mice. Tumor volume was documented once 7 days after implantation. REF000639 ICD-11: 2A00 Glioma CELL10068; CELL00392; CELL00295; CELL00043 HEB; SF126; U87; U251 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00476 NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11. Inducer Down regulation . . Suppressor . Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 106 U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm3, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks. REF000635 ICD-11: 2A00 Glioblastoma CELL00295; CELL00043 U87; U251 NF-kappa B signaling pathway (hsa04064); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00613 Our hypothesis and results provided proof that boric acid prevent tumor progression by regulation of ferroptosis, apoptosis and semaphorin signaling pathway. BA was found to have more effective on SEMA3F/NP2 upregulated against C6 untreated cells. What's more, the novel anticancer candidate drug effect of BA were principally associated with the ACSL4/GPX4, TOS/TAS biochemical marker and SEMA3F/NP2 signaling pathways. Dose-decently BA induced oxidative and ferroptosis in Glioblastoma multiform. Inducer Up regulation . . Driver . . REF000839 ICD-11: 2A00 Glioblastoma CELL00593 C6 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00614 Our hypothesis and results provided proof that boric acid prevent tumor progression by regulation of ferroptosis, apoptosis and semaphorin signaling pathway. BA was found to have more effective on SEMA3F/NP2 upregulated against C6 untreated cells. What's more, the novel anticancer candidate drug effect of BA were principally associated with the ACSL4/GPX4, TOS/TAS biochemical marker and SEMA3F/NP2 signaling pathways. Dose-decently BA induced oxidative and ferroptosis Glioblastoma multiform. Inducer Up regulation . . Driver . . REF000839 ICD-11: 2A00 Glioblastoma CELL00593 C6 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01567 miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells. Upregulation of miR-127-5p increased LDH, MDA, and ROS levels and Fe2+ content and inhibited the expression of GPX4 protein. . . . Up regulation Suppressor Suppressor Meningioma model mice were constructed as follows: after abdominal skin disinfection, 1% pentobarbital sodium (135 pL) was intraperitoneally injected into the nude mice. The head of the nude mice was fixed with a stereotaxometer, and two ear needles were symmetrically fixed in the bony parts slightly in front of each ear of the nude mice. The skin of the head of nude mice was cut approximately 0.6 cm lengthwise at 5 mm after the intersection of the inner canthal line and sagittal midline. The skin and fascia on both sides of the incision were bluntly separated with forceps to fully expose the skull. The location of the drill hole was determined according to the stereotactic anatomical map of the head: 0.5 mm behind the intersection of the coronal and sagittal suture and 2.5 mm to the right of the midline. The electric drill drilled a hole of approximately 1 mm at this position. The cells of the third generation of the logarithmic growth stage were taken. The cell suspension was absorbed with a 10 uL microsyringe, and the needle was slowly injected vertically to a depth of approximately 1.5 mm. The cell suspension (5 x 105 cells/100 uL) was slowly injected, and the needle remained for 2 min after injection before being slowly withdrawn. REF000776 ICD-11: 2A01 Meningiomas CELL10030; CELL10018; CELL10030; CELL00465; CELL10078 HMCs; HUM-iCell-n002; iCell; IOMM-Lee; CTCC-400-0154 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique01566 miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells. Upregulation of miR-127-5p increased LDH, MDA, and ROS levels and Fe2+ content and inhibited the expression of GPX4 protein. . . . Down regulation Driver Suppressor Meningioma model mice were constructed as follows: after abdominal skin disinfection, 1% pentobarbital sodium (135 pL) was intraperitoneally injected into the nude mice. The head of the nude mice was fixed with a stereotaxometer, and two ear needles were symmetrically fixed in the bony parts slightly in front of each ear of the nude mice. The skin of the head of nude mice was cut approximately 0.6 cm lengthwise at 5 mm after the intersection of the inner canthal line and sagittal midline. The skin and fascia on both sides of the incision were bluntly separated with forceps to fully expose the skull. The location of the drill hole was determined according to the stereotactic anatomical map of the head: 0.5 mm behind the intersection of the coronal and sagittal suture and 2.5 mm to the right of the midline. The electric drill drilled a hole of approximately 1 mm at this position. The cells of the third generation of the logarithmic growth stage were taken. The cell suspension was absorbed with a 10 uL microsyringe, and the needle was slowly injected vertically to a depth of approximately 1.5 mm. The cell suspension (5 x 105 cells/100 uL) was slowly injected, and the needle remained for 2 min after injection before being slowly withdrawn. REF000776 ICD-11: 2A01 Meningiomas CELL10030; CELL10018; CELL10030; CELL00465; CELL10078 HMCs; HUM-iCell-n002; iCell; IOMM-Lee; CTCC-400-0154 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique00637 Subsequent studies have revealed that Polygonatum cyrtonemaHua Polysaccharides (PCP) alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. PCP has the development potential as a new drug candidate for treating CNS diseases. Suppressor . Up regulation . . Suppressor . REF000872 ICD-11: 2A02 CNS diseases CELL00544 BV2 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00636 Subsequent studies have revealed that Polygonatum cyrtonemaHua Polysaccharides (PCP) alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. PCP has the development potential as a new drug candidate for treating CNS diseases. Suppressor . Up regulation . . Marker/Suppressor . REF000872 ICD-11: 2A02 CNS diseases CELL00544 BV2 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00182 Ferroptosis may account for the main mechanisms of how decitabine induced death of myelodysplastic syndrome (MDS) cells. Decitabine-induced ROS raise leads to ferroptosis in MDS cells by decreasing GSH level and GPX4 activity. Inducer . Down regulation . . Suppressor C57BL/6 mice were purchased from Vital River (Beijing, China) at 6 to 8 weeks of age. Twenty mice were housed with five individuals per cage and used at a weight of approximately 20.0-22.0 g. They were randomly divided into four groups, five in each group, namely control group, low-dose group, middle-dose group, and high-dose group. The low-, middle-, and high-dose group mice were administered an intraperitoneal injection of 0.2-ml iron dextran at a concentration of 6.25, 12.5, and 25 mg/ml, respectively, every 3 days for 10 weeks to establish iron overload model. At the same time, normal saline was given to the control group. REF000240 ICD-11: 2A3Z Myelodysplastic syndrome CELL00064; CELL00373 SKM-1; MUTZ-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell necroptosis
unique00877 Dihydroartemisinin (DHA) strongly inhibited the viability of acute myeloid leukemia (AML) cell lines and arrest cell cycle at G0/G1 phase. ISCU over-expression robustly alleviated the iron starvation response through regulating the expression of IRPs and downstream FTH. ISCU significantly attenuated DHA induced ferroptosis by regulating iron metabolism, rescuing the mitochondrial function and increasing the level of GSH. . . . Up regulation Suppressor Marker/Suppressor BALB/c Nude Mice (4 weeks old) were obtained from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with HL60 cells (1 x 107, suspended in 0.1 mL PBS). After tumors reached 100-200 mm3, the mice were randomly assigned to two groups. DHA was administered intraperitoneal injection once a day at 50 mg/kg body weight and the mice in normal control were received equal amounts of vehicle (10% DMSO in sterile corn oil). On the 28th day, mice were euthanized. The tumor volumes were measured every 4 days with a caliper. REF000057 ICD-11: 2A60 Acute myeloid leukemia CELL00035; CELL00588; CELL00038 HL60; KG1; THP-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation; Cell cycle
unique00484 Sulforaphane triggers different types of PCD in a concentration-dependent manner on the two tested acute myeloid leukemia cell lines. Deepening the molecular mechanisms on U-937 cells, we discovered that at lower concentrations, SFN induces apoptosis; at higher concentrations, SFN elicits ferroptosis, characterized by the depletion of intracellular GSH, the downregulation of GPX4 protein expression, and lipid peroxidation. Inducer . Down regulation . . Suppressor . REF000643 ICD-11: 2A60 Acute myeloid leukemia CELL00039; CELL00058 U-937; MV4-11 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00741 We investigated and characterized its antileukemic potential in vitro, disclosing its ability to trigger ferroptosis. Specifically, perillaldehyde induced lipid peroxidation, decreased glutathione peroxidase 4 protein expression, and depleted intracellular glutathione on HL-60 promyelocytic leukemia cells. Inducer . Down regulation . . Suppressor . REF000964 ICD-11: 2A60 Acute myeloid leukemia CELL00059; CELL00083; CELL00042; CELL00035 Jurkat; DLD-1; SHSY5Y; HL-60 Glutathione metabolism (hsa00480) Cell ferroptosis
unique00233 APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia (AML). The association of APR-246 with induction of ferroptosis (either by pharmacological compounds, or genetic inactivation of SLC7A11 or GPX4) had a synergistic effect on the promotion of cell death, both in vivo and ex vivo. Inducer . Down regulation . . Suppressor Xenograft tumors were generated by randomly injecting 1 x 106 MOLM14 shCTRL or shSLC7A11 cells into the tail veins of NOD/SCID IL-2 receptor g-chain-null mice (NSG) aged 6-9 weeks. Fourteen days after injection, doxycycline (200 mg/mL) and sucrose (1% weight:volume) were added to the drinking water of these animals. After 3 days, the mice were randomly treated with a daily intraperitoneal injection of APR-246 (100 mg/kg) or vehicle (phosphate-buffered saline [PBS]) for 4 days. REF000299 ICD-11: 2A60 Acute myeloid leukemia CELL00035; CELL00311; CELL00406; CELL00058; CELL00386; CELL00396; CELL00036; CELL00038; CELL00457; CELL00064; CELL00037; CELL00020 HL60; MOLM14; SET2; MV4-11; OCI-AML2; OCI-AML3; K562; THP1; UT7-EPO; SKM1; NB4; KASUMI Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00989 Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects acute myeloid leukemia cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells. . . . Down regulation Driver Suppressor Six- to 12-week-old Aldh-mut and Aldh-Ctrl mice were used to generate MLL-AF9 leukemia through retroviral transduction. This was transplanted into lethally irradiated (9 Gy) primary leukemic C57BL/6J mice and then into sublethally irradiated (4.5 Gy) secondary leukemic C57BL/6J mice. Forty-eight hours after injection into secondary recipients, these mice received 3 doses of polyinosinic-polycytidylic acid (GE Healthcare) on alternate days. REF000182 ICD-11: 2A60 Acute myeloid leukemia CELL00035; CELL00311; CELL00372; CELL00037; CELL00207; CELL00038 HL60; MOLM-14; MONOMAC-6; NB4; NOMO-1; THP1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00540 Honokiol decreased the viability of the targeted Acute myeloid leukemia cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. And HMOX1 was a critical target in honokiol-induced ferroptosis. Inducer . Up regulation . . Driver . REF000750 ICD-11: 2A60 Acute myeloid leukemia CELL00038; CELL00039; CELL00064 THP-1; U-937; SKM-1 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00129 ATPR, a novel all-trans retinoic acid (ATRA) derivative, has been extensively developed to show superior anticancer effect than ATRA in acute myeloid leukemia (AML). ATPR-induced ferroptosis was regulated by autophagy via iron homeostasis, especially Nrf2. Inducer . Down regulation . . Marker/Suppressor Six- to seven-week-old female NCG mice were obtained from the Nanjing model animal research institute (Nanjing, China). Mice were raised in individually ventilated cages of Anhui Medical University (Hefei, China). Then, an injection of NB4 cells (5 x 106/100 ul) suspended in chilled Matrigel and PBS (1:1) was given into the right flank of each mouse. For each experiment, the animals (n = 12) were randomly allocated into the two groups and treated with solvent or 10 mg/kg ATPR (intraperitoneal injection, once every other day) for 7 days. REF000188 ICD-11: 2A60 Acute myeloid leukemia CELL00037; CELL00035; CELL00039 NB4; HL-60; U937 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00254 Indole-3-pyruvate (I3P) suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program in Childhood acute monocytic leukemia. And I3P elevated the activation of compensatory gene expression as indicated by increased protein amounts of SLC7A11 and HO-1, two important target genes of anti-oxidative stress pathways. Suppressor . Up regulation . . Suppressor . REF000340 ICD-11: 2A60 Childhood acute monocytic leukemia CELL00038; CELL00337; CELL00057; CELL00095; CELL00554; CELL00049 THP-1; RS4; HEK293T; HT-1080; NIH3T3; Hela Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00962 Since KDM3B has been shown to associate with acute myeloid leukemia (AML). KDM3B protects cells from Erastininduced ferroptosis through transcriptional upregulation of SLC7A11 via interaction with ATF4. . . . Up regulation Suppressor Suppressor . REF000139 ICD-11: 2A60 Acute myeloid leukemia CELL00095; CELL00004; CELL00038 HT-1080; 293; THP-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00878 Dihydroartemisinin (DHA) strongly inhibited the viability of acute myeloid leukemia (AML) cell lines and arrest cell cycle at G0/G1 phase. Mechanistically, DHA induced autophagy by regulating the activity of AMPK/mTOR/p70S6k signaling pathway, which accelerated the degradation of ferritin, increased the labile iron pool, promoted the accumulation of cellular ROS and eventually led to ferroptotic cell death. Inducer Up regulation . . Driver . BALB/c Nude Mice (4 weeks old) were obtained from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with HL60 cells (1 x 107, suspended in 0.1 mL PBS). After tumors reached 100-200 mm3, the mice were randomly assigned to two groups. DHA was administered intraperitoneal injection once a day at 50 mg/kg body weight and the mice in normal control were received equal amounts of vehicle (10% DMSO in sterile corn oil). On the 28th day, mice were euthanized. The tumor volumes were measured every 4 days with a caliper. REF000057 ICD-11: 2A60 Acute myeloid leukemia CELL00035; CELL00588; CELL00038 HL60; KG1; THP-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation; Cell cycle
unique00041 Typhaneoside (TYP) significantly triggered autophagy in acute myeloid leukemia (AML) cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately. Inducer Up regulation . . Driver . 4-week-old BALB/c malenude mice(Peking University Health Science Center, Beijing, China) were subcutaneously injection with HL60 cells (1 x 107). After tumor volume reached 50 mm3, mice were randomly divided into 4 groups (n = 16/group). TYP was administered intraperitoneal injection once a day at 10, 20 and 30 mg/kg body weight and the mice in normal control group were received equal amounts of 10% DMSO in sterile corn oil. REF000076 ICD-11: 2A60 Acute myeloid leukemia CELL00495; CELL00035; CELL00037; CELL00036; CELL00057 Kas-1; HL60; NB4; K562; 293T Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation; Cell apoptosis; Cell autophagy
unique00763 Dihydroartemisinin (DHA) activated zinc metabolism signaling, especially the upregulation of metallothionein (MT). DHA activates ferritinophagy and subsequent ferroptosis in AML and that MTs are involved in glutathione regenerating and antioxidant response in Acute Myeloid Leukemia. Inducer Up regulation . . . . . REF000985 ICD-11: 2A60 Acute myeloid leukemia CELL00311; CELL00386; CELL00035; CELL00406; CELL00058; CELL00036; CELL00038; CELL00457; CELL00064; CELL00037; CELL00020 MOLM-14; OCI-AML2; HL-60; SET2; MV4-11; K562; THP-1; UT7-EPO; SKM1; NB4; KASUMI-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01806 EZH2 inhibition upregulated-TfR-1 dysregulation leads to drug resistance in EZH2 WT diffuse large B-cell lymphoma (DLBCL). On the other hand, EZH2i impaired the occurrence of ferroptosis by upregulating the heat shock protein family A (Hsp70) member 5 (HSPA5) and stabilizing glutathione peroxidase 4 (GPX4), a ferroptosis suppressor. . . . Up regulation Suppressor Suppressor All animal experiments were approved by the Institutional Animal Care and Use Committee of Shanghai Institute of Materia Medica and performed in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care. Tumors were measured twice weekly and volumes were calculated using the formula TV=length x width2 x 1/2. REF001036 ICD-11: 2A81 Diffuse large B-cell lymphoma CELL00180; CELL00234; CELL00399; CELL00057 KARPAS-422; U-2932; WILL-2; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00021 Imidazole ketone erastin (IKE) is a potent, selective, and metabolically stable system xc- (SLC7A11)inhibitor. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model. Inducer . Down regulation . . Suppressor NOD/SCID mice (12-weeks of age and ~28 g weight) were weighed before injection and divided into groups of 3 mice per cage. Mice were dosed using three different routes, IP and PO with 50 mg/kg IKE, and IV with 17 mg/kg IKE. Samples were collected at 0, 1, 3, 4, and 8 h from three mice per time point. Additionally, three mice per group were used as controls by administration with equivalent amount of vehicle 1 by IP, PO, and IV, and samples were collected at 8 h. At the appropriate time, mice were sacrificed by CO2 asphyxiation for 3 min and ~0.5 mL of blood was collected via cardiac puncture. REF000060 ICD-11: 2A81 Diffuse large B-cell lymphoma CELL00346; CELL00314; CELL00242; CELL00407; CELL00397; CELL00398; CELL00356; CELL00539; CELL00039; CELL00363; CELL00524; CELL00234; CELL00443; CELL00442; CELL00357; CELL00231; CELL00227; CELL00180 SUDHL-1; SUDHL-2; SUDHL-6; SUDHL-8; SUDHL-10; SUDHL-16; A3/KAW; RIVA; Ly8; U937; DOHH-2; HBL-1; U2932; SUDHL-7; SUDHL-9; A4/FUK; WSU-NHL; SUDHL-5; Karpas422 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01805 EZH2 inhibition upregulated-TfR-1 dysregulation leads to drug resistance in EZH2 WT diffuse large B-cell lymphoma (DLBCL). On the other hand, EZH2i impaired the occurrence of ferroptosis by upregulating the heat shock protein family A (Hsp70) member 5 (HSPA5) and stabilizing glutathione peroxidase 4 (GPX4), a ferroptosis suppressor. . . . Down regulation Suppressor Marker/Suppressor/Driver All animal experiments were approved by the Institutional Animal Care and Use Committee of Shanghai Institute of Materia Medica and performed in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care. Tumors were measured twice weekly and volumes were calculated using the formula TV=length x width2 x 1/2. REF001036 ICD-11: 2A81 Diffuse large B-cell lymphoma CELL00180; CELL00234; CELL00399; CELL00057 KARPAS-422; U-2932; WILL-2; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00278 Dimethyl fumarate (DMF) induces lipid peroxidation and thus ferroptosis, particularly in GCB diffuse large B-cell lymphoma (DLBCL). In ABC DLBCL cells, which are addicted to NF-kB and STAT3 survival signaling, DMF treatment efficiently inhibits the activity of the IKK complex and Janus kinases . Inducer Down regulation . . Suppressor . For the VFN-D1 patient-derived and the HBL-1 xenograft mouse models, adult female NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were implanted subcutaneously with 1 x 107 cells in PBS (300 ul). Once mice developed palpable tumors, the animals were randomized into control, DMF (daily i.p. treatment with 500 ul of 3 mg/ml DMF in PBS), ABT-199 (daily p.o. treatment with 100 mg/kg in ethanol/PhosalG/PEG400) or DMF+ABT-199 treated groups. REF000388 ICD-11: 2A81 Diffuse large B-cell lymphoma CELL00052; CELL00045; CELL00053; CELL00095; CELL00012; CELL00609; CELL00017; CELL00057 MCL; A431; A549; HaCaT; HT1080; Huh7; SK-MEL-28; SMMC-7721; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01283 Artesunate (ART) was found to exert its effects via inhibition of STAT3 activation. ART may induce apoptosis and cell cycle arrest to inhibit cell proliferation, and regulate autophagy and ferroptosis via impairing the STAT3 signaling pathway in diffuse large B cell lymphoma (DLBCL) cells. Inducer Down regulation . . Suppressor . Female NOD/SCID mice (age, 6 weeks; body weight, 20 ± 2 g) were purchased from Beijing Huafukang Biotechnology Co., Ltd., maintained under pathogen-free conditions and allowed free access to sterilized food and water. After a week of adaptation to their surroundings, 1 x 107 U2932 cells were subcutaneously injected into the right flank near the hind leg of each mouse. Following the growth of palpable tumors (tumor volume of 50-100 mm3), the mice were randomly divided into two groups (n = 5 mice/group) and treated with 100 ul normal saline (NS) or ART (120 mg/kg/day) via intraperitoneal injection. REF000536 ICD-11: 2A81 Diffuse large B-cell lymphoma CELL00234; CELL00314; CELL00129; CELL00242; CELL00057 U2932; SU-DHL2; SU-DHL4; SU-DHL6; 293T JAK-STAT signaling pathway (hsa04630); Ferroptosis (hsa04216); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique01818 Ginsenoside Rh4 inhibited SIRT2 expression in multiple myeloma (MM) cells. The overexpression of SIRT2 reversed the effects of ginsenoside Rh4 on cell proliferation, cell apoptosis, cycle arrest and ferroptosis in MM. Overall, ginsenoside Rh4 inhibited the malignant progression of MM and induced ferroptosis by regulating SIRT2. Inducer Down regulation . . Suppressor . . REF001048 ICD-11: 2A83.1 Multiple myeloma CELL00206 NCI-H929 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis; Cell cycle
unique01775 Mechanistically, the direct binding of Nitidine chloride (NC) to ABCB6 suppressed PI3K/AKT signaling pathway to promote ferroptosis. In conclusion, ABCB6 can be a potential therapeutic target and prognostic biomarker in Multiple myeloma (MM), while NC can be considered a novel drug for MM treatment. Inducer . . . Suppressor . Male BALB/c nude mice, aged 5 weeks, were procured from Guangzhou Ruige biology Model Animal Research Center (No. 44827200001656, Guangzhou, China). Tumor xenograft assay was performed by dissolving SP2/0 cells in PBS (1 x 106/200 uL) and subcutaneously inoculating them into the right flank of mice. After the tumor reached 50 mm3, the tumor-bearing mice were randomly separated into three groups and intraperitoneally administered with NC (4.6 or 6 mg/kg) every two days. Body masses and tumor sizes were determined every day. Subsequently, the mice were sacrificed, and the inhibition of tumor growth and the tumor masses were determined. Later, visceral organs and tumors from every group were harvested and immobilized in paraformaldehyde (4%). All murine experimental procedures conformed to the National Institute of Health Guide for the Care and Use of Laboratory Animals. REF001006 ICD-11: 2A83.1 Multiple myeloma CELL00138; CELL00001; CELL00570 U266; 8226; SP2/0 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00282 Using T cell acute lymphoblastic leukemia (T-ALL) cell lines Jurkat and Molt-4 as model system, Hydnocarpin D (HD) suppressed T-ALL proliferationin vitro, via induction of cell cycle arrest and subsequent apoptosis. Furthermore, HD increased the MAP1LC3B (LC3-II) levels and the formation of autophagolysosome vacuoles, both of which are markers for autophagy. Inducer Up regulation . . Driver . . REF000394 ICD-11: 2A90 T-cell acute lymphoblastic leukemia CELL00059; CELL00041; CELL00319 Jurkat; Molt-4; CAM-191 Ferroptosis (hsa04216); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00684 Triptolide inhibited Nrf2 expression and induced leukemia cell ferroptosis, as evidenced by increased ROS levels and lipid oxidation as well as decreased glutathione peroxidase 4 expression. Therefore, it is plausible that triptolide can promote leukemia cell sensitivity to DOX via downregulation of Nrf2 expression. Inducer . Down regulation . . Marker/Suppressor . REF000906 ICD-11: 2B33 Myeloid leukaemia CELL00036; CELL00035; CELL00057 K562; HL-60; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01164 PAQR3 inhibited proliferation and aggravated ferroptosis in acute lymphoblastic leukemia through modulation Nrf2 stability. This study suggested that PAQR3 may serve as an effective biological marker for ALL treatment. . . . Down regulation Driver Marker/Suppressor . REF000402 ICD-11: 2B33 Acute lymphoblastic leukemia CELL00146; CELL00041; CELL00435; CELL00059 MOLT3; MOLT4; CEMC1; Jurkat Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00895 HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice. . . . Up regulation Driver Marker Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection. REF000067 ICD-11: 2B33 Myeloid leukaemia CELL00035; CELL00037; CELL00105; CELL00039; CELL00038 HL-60; NB4; KG-1; U937; THP-1 Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy
unique00894 HMGB1 could be a potential drug target for therapeutic interventions in leukemia.Importantly, these data were further supported by our in vivo experiment, in which xenografts formed by HMGB1 knockdown HL-60/NRASQ61L cells had lower PTGS2 and TfR1 expression than that in control mice. . . . Up regulation Driver Marker/Suppressor/Driver Seven- to eight-week male NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice that weighed about 20 g were purchased from Xiangya Medical College Animal Laboratory (Changsha, China). Indicated HL-60/NRASQ61L cells were subcutaneously injected into the dorsal flanks right of the midline in NOD/SCID mice (weight, approximately 20 g). At day seven, mice were intraperitoneal injected with erastin (20 mg/kg i.v., three times a week) for two weeks. Erastin was dissolved in the vehicle (2% DMSO and 98% PBS) and prepared by Ultrasonic Cleaner (Fisher Scientific, Hampton, NH). A final volume of 300 uL of erastin was applied via intraperitoneal injection. REF000067 ICD-11: 2B33 Myeloid leukaemia CELL00035; CELL00037; CELL00105; CELL00039; CELL00038 HL-60; NB4; KG-1; U937; THP-1 Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy
unique01823 MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4. . . . Down regulation Suppressor Driver The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse). REF001051 ICD-11: 2B51 Osteosarcoma CELL00245; CELL00131; CELL00113; CELL00134; CELL00055; CELL10086 h143B; SW1353; MG-63; SaOS-2; U2OS; HOB Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01825 MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4. . . . Up regulation Driver Driver The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse). REF001051 ICD-11: 2B51 Osteosarcoma CELL00245; CELL00131; CELL00113; CELL00134; CELL00055; CELL10086 h143B; SW1353; MG-63; SaOS-2; U2OS; HOB Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00472 Ursolic acid inhibited tumour cell proliferation and promoted the apoptosis of a variety of osteosarcoma cells. Mechanistic studies showed that ursolic acid degraded ferritin by activating autophagy and induced intracellular overload of ferrous ions, leading to ferroptosis. Ferritin, which includes ferritin light peptide 1 (FTL1) and ferritin heavy peptide 1 (FTH1). Inducer . Down regulation . . Marker/Suppressor NU/NU mice (the Fourth Military Medical University, Shaanxi, China) were injected with 143B cells (100 uL, 5 x 107 cells/mL, i.h.). Seven days after the injection, the mice were divided into 6 different groups (n= 3) and intraperitoneally injected with different drugs twice a week. Then, on day 28, the mice were sacrificed, and the tumours in the different groups were weighed. Body weight and tumour size were measured every 3 days from day 7 to day 28. The tumour tissue was fixed with 4% paraformaldehyde, embedded in paraffin, and cut into 4 um thick sections for haematoxylin-eosin (H&E) and immunofluorescence staining. REF000630 ICD-11: 2B51 Osteosarcoma CELL00094; CELL00245 HOS; 143B Ferroptosis (hsa04216); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis; Cell autophagy
unique00420 Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression. Inducer . Down regulation . . Marker/Suppressor . REF000563 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00094 MG63; HOS Ferroptosis (hsa04216) Cell ferroptosis
unique00473 Ursolic acid inhibited tumour cell proliferation and promoted the apoptosis of a variety of osteosarcoma cells. Mechanistic studies showed that ursolic acid degraded ferritin by activating autophagy and induced intracellular overload of ferrous ions, leading to ferroptosis. Ferritin, which includes ferritin light peptide 1 (FTL1) and ferritin heavy peptide 1 (FTH1). Inducer . Down regulation . . Suppressor NU/NU mice (the Fourth Military Medical University, Shaanxi, China) were injected with 143B cells (100 uL, 5 x 107 cells/mL, i.h.). Seven days after the injection, the mice were divided into 6 different groups (n= 3) and intraperitoneally injected with different drugs twice a week. Then, on day 28, the mice were sacrificed, and the tumours in the different groups were weighed. Body weight and tumour size were measured every 3 days from day 7 to day 28. The tumour tissue was fixed with 4% paraformaldehyde, embedded in paraffin, and cut into 4 um thick sections for haematoxylin-eosin (H&E) and immunofluorescence staining. REF000630 ICD-11: 2B51 Osteosarcoma CELL00094; CELL00245 HOS; 143B Ferroptosis (hsa04216); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis; Cell autophagy
unique00421 Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression. Inducer . Down regulation . . Suppressor . REF000563 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00094 MG63; HOS Ferroptosis (hsa04216) Cell ferroptosis
unique00815 By promoting the Fe accumulation, ROS formation, MDA production and suppressing the ratio of GSH/GSSG, baicalin was found to trigger ferroptosis in Osteosarcoma and ferroptosis inhibitor ferrostatin-1 (Fer-1) successfully reversed these suppressive effects, indicating that ferroptosis participated in the baicalin mediated anti-OS activity. Mechanistically, baicalin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced its stability via inducing ubiquitin degradation, which suppressed the Nrf2 downstream targets GPX4 and xCT expression, and led to stimulating ferroptosis. Inducer . Down regulation . . Suppressor A total of 24 BALB/c-nude mice (4-5 weeks old) were purchased and MG63 cells were injected into the right tibial bone marrow cavity of mice in a volume of 1 x 106/100 ul. When the tumor volume was visible, all animals were randomly divided into four groups (n = 6): the control (10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline) group, the baicalin (200 mg/kg/day) group, the Fer-1 (0.8 mg/kg/day) group and Fer-1 + baicalin group. The baicalin and Fer-1 were intraperitoneally administered every day for two consecutive weeks and tumor sizes were measured every two days. REF001033 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00245; CELL10020 MG63; 143B; hBMSCs Ferroptosis (hsa04216) Cell ferroptosis
unique01824 MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4. . . . Up regulation Suppressor Suppressor The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse). REF001051 ICD-11: 2B51 Osteosarcoma CELL00245; CELL00131; CELL00113; CELL00134; CELL00055; CELL10086 h143B; SW1353; MG-63; SaOS-2; U2OS; HOB Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01826 MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of osteosarcoma (OS) cells. The overexpression of ZEB1 caused the lower expression level of ACSL4 and higher expression level of xCT and GPX4. . . . Down regulation Driver Suppressor The OS model of nude mice was constructed using the CDTX model. After transfection, the h143B cells were prepared into a single-cell suspension and subcutaneously injected into the left proximal tibia of 36 (3 mice per group) 4-weeks-old nude mice (1 x 107 cells per mouse). REF001051 ICD-11: 2B51 Osteosarcoma CELL00245; CELL00131; CELL00113; CELL00134; CELL00055; CELL10086 h143B; SW1353; MG-63; SaOS-2; U2OS; HOB Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00487 MiR-1287-5p directly bound to the 3'-untranslated region of glutathione peroxidase 4 (GPX4) to inhibit its protein level and activity, and that GPX4 overexpression completely abolished the miR-1287-5p mimic-mediated ferroptotic induction and tumor suppression. The findings prove that miR-1287-5p promotes ferroptosis of osteosarcoma cells through inhibiting GPX4. . . . Down regulation Driver Suppressor . REF000649 ICD-11: 2B51 Osteosarcoma CELL00269; CELL00134; CELL00055 hFOB1.19; SaOS2; U2OS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00236 3,5-bis((E)-2-fluorobenzylidene)piperidin-4-one hydrochloride (EF24) upregulated HMOX1 to suppress GPX4 expression to induce ferroptosis by increasing MDA level, ROS level and intracellular ferric ion level. Thus, EF24 might serve as a potential agent for the treatment of HMOX1-positive osteosarcoma patients. Inducer . Up regulation . . Driver/Suppressor . REF000304 ICD-11: 2B51 Osteosarcoma CELL00055; CELL00134 U2os; Saos-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00728 Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. Inducer . Up regulation . . Driver . REF000947 ICD-11: 2B51 Osteosarcoma CELL00057; CELL00113; CELL00055; CELL00014 293T17; MG63; U2-OS; HOS-MNNG Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00814 By promoting the Fe accumulation, ROS formation, MDA production and suppressing the ratio of GSH/GSSG, baicalin was found to trigger ferroptosis in Osteosarcoma and ferroptosis inhibitor ferrostatin-1 (Fer-1) successfully reversed these suppressive effects, indicating that ferroptosis participated in the baicalin mediated anti-OS activity. Mechanistically, baicalin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced its stability via inducing ubiquitin degradation, which suppressed the Nrf2 downstream targets GPX4 and xCT expression, and led to stimulating ferroptosis. Inducer . Down regulation . . Marker/Suppressor A total of 24 BALB/c-nude mice (4-5 weeks old) were purchased and MG63 cells were injected into the right tibial bone marrow cavity of mice in a volume of 1 x 106/100 ul. When the tumor volume was visible, all animals were randomly divided into four groups (n = 6): the control (10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline) group, the baicalin (200 mg/kg/day) group, the Fer-1 (0.8 mg/kg/day) group and Fer-1 + baicalin group. The baicalin and Fer-1 were intraperitoneally administered every day for two consecutive weeks and tumor sizes were measured every two days. REF001033 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00245; CELL10020 MG63; 143B; hBMSCs Ferroptosis (hsa04216) Cell ferroptosis
unique00727 Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells. Inducer . Up regulation . . Marker . REF000947 ICD-11: 2B51 Osteosarcoma CELL00057; CELL00113; CELL00055; CELL00014 293T17; MG63; U2-OS; HOS-MNNG Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00419 Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 (SLC11A2) expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression. Inducer . Up regulation . . Driver . REF000563 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00094 MG63; HOS Ferroptosis (hsa04216) Cell ferroptosis
unique00308 SLC7A11 overexpression could restored the proliferation and migration abilities inhibited by Tirazamine. Thus, TPZ could inhibit the proliferation and migration of osteosarcoma cells, and induce ferroptosis in part through inhibiting SLC7A11. Inducer . Down regulation . . Suppressor . REF000436 ICD-11: 2B51 Osteosarcoma CELL00245; CELL00014; CELL00055 143B; MNNG/Hos; U2OS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01110 KDM4A regulates SLC7A11 transcription and osteosarcoma cell ferroptosis by controlling H3K9me3 demethylation in the promoter region of SLC7A11. The findings suggestes that KDM4A activity may be a potential therapeutic target for future OS treatment. . . . Up regulation Suppressor Suppressor For the xenograft mouse model, 1 x 106 OS 143B cells in 100 uL PBS were subcutaneously injected with 1 x 106 OS cells. For the OS lung metastasis model and in vivo imaging, 1 x 106 143B cells in 10 uL PBS were injected orthotopically into the medullary cavity of the tibia of mice. For bioluminescent imaging, we used 143B cells stably expressing luciferase, and the luciferase substrate D-Luciferin (Selleck, China) was retro-orbitally injected before imaging on days 7 and 21. REF000353 ICD-11: 2B51 Osteosarcoma CELL00245; CELL00094 143B; HOS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell metastasis
unique01713 LncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. In conclusion, our findings highlight the involvement of lncRNA SNHG14 in ferroptosis and chemotherapy resistance of nutlin3a-resistant NR-SJSA1 cells, thus shedding new insight on how to overcome drug resistance in osteosarcoma cells and improve treatment efficacy. . . . Down regulation Driver Suppressor . REF000932 ICD-11: 2B51 Osteosarcoma CELL00220 NR-SJSA1 Ferroptosis (hsa04216) Cell ferroptosis
unique01712 LncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. In conclusion, our findings highlight the involvement of lncRNA SNHG14 in ferroptosis and chemotherapy resistance of nutlin3a-resistant NR-SJSA1 cells, thus shedding new insight on how to overcome drug resistance in osteosarcoma cells and improve treatment efficacy. . . . Up regulation Suppressor Suppressor . REF000932 ICD-11: 2B51 Osteosarcoma CELL00220 NR-SJSA1 Ferroptosis (hsa04216) Cell ferroptosis
unique00418 Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression. Inducer . Up regulation . . Marker/Suppressor/Driver . REF000563 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00094 MG63; HOS Ferroptosis (hsa04216) Cell ferroptosis
unique00787 Zoledronic acid (ZOL) induces ferroptosis by upregulating POR expression to increase ROS levels and upregulate lipid peroxidation levels in osteosarcoma cells. POR may be used as a therapeutic target to inhibit osteosarcoma. Inducer Up regulation . . Driver . All animal experimentation was approved by the Ethics Committee of The Eighth Affiliated Hospital of Sun Yat-sen University. Each group consisted of five female BALB/c nude 4-week-old mice, and the studies were run twice. 143B cells were treated with ZOL or DMEM containing 10% FBS for 2 days. Two sets of BALB/c nude mice were used in the study (ZOL group and NC group). The ZOL group and NC group were subcutaneously injected with ZOL-treated 143B cells or normal 143B cells, respectively, to form xenograft tumors. After 2 weeks, we subcutaneously injected 100 ul ZOL (100 ug/kg) into the experimental group and 100 ul saline into the NC group twice a week. Then, after 4 weeks, mice from both groups were humanely killed, the tumor diameter was measured, and the tumor tissue was stained with HE. REF001005 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00245 MG63; 143B Ferroptosis (hsa04216) Cell ferroptosis
unique00838 The resulting dependency of ZEB1-high cells on lipid-peroxidase activity is most effectively exploited by direct inhibition of GPX4 in Fibrosarcoma. . . . Down regulation Driver Suppressor Xenografts for LOXIMVI sgEGFP (WT) and LOXIMVI sgGPX4 (KO) cells were established by injecting 10 million cells in a 1:1 PBS:Matrigel mixture containing 2.5 uM ferrostatin-1 into the flanks of athymic mice (NRC Nude, Taconic). Animals were dosed daily with 2 mg kg-1 ferrostatin-1 by intraperitoneal injections. Tumour volume was measured twice a week. REF000020 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00189; CELL00139; CELL00431; CELL00365; CELL10037; CELL10064; CELL00002; CELL00201; CELL00172; CELL00528; CELL00527; CELL10105; CELL10106 HT-1080; LOXIMVI; WI38; RKN; KP4; Mesenchymal stem cells (MSCs); HUVECs; CD34; BJeH foreskin fibroblasts; MCF-7; H358; HCC4006; M000921; M980513; AA01; AA02 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00014 FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. FINO2 both indirectly inhibits GPX4 enzymatic function and directly oxidizes iron, ultimately causing widespread lipid peroxidation in Fibrosarcoma. Inducer . Down regulation . . Suppressor . REF000039 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00475; CELL10062; CELL00081 HT-1080; BJ-5ta; BJ-eLR; CAKI-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00959 IDH2 is major enzyme that produces NADPH, which is essential for GSH turnover. The data suggest that decreased growth of tumors with IDH2-knockdown is due to inhibition of Gpx4 followed by a shortage of GSH, resulting in ferroptotic cell death in Fibrosarcoma. . . . Up regulation Suppressor Suppressor Eight week-old male nude mice weighing approximately 21-23 g were divided into two groups (DMSO group and erastin group) with 5 mice per group. Each mouse was injected with 5 x 106 cells transfected non-targeting shRNA and idh2-targeting shRNA on the left and right hind legs, respectively. Erastin was administered intraperitoneally at 5 mg/kg for 15 consecutive days starting on the same day as tumor injection. REF000136 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00009 HT1080; Hepa1-6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01010 Reduced NCOA4 expression resulted from a lower rate of hypoxic NCOA4 transcription combined with a micro RNA 6862-5p-dependent degradation of NCOA4 mRNA, the latter being regulated by c-jun N-terminal kinase (JNK). Pharmacological inhibition of JNK under hypoxia increased NCOA4 and prevented FTMT induction in Fibrosarcoma. . . . Down regulation Suppressor Driver . REF000216 ICD-11: 2B53 Fibrosarcoma CELL00095 HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00892 Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma. . . . Down regulation Driver Suppressor Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 106 tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 106 luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse. REF000064 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00069; CELL00555; CELL00584 HT-1080; A375; B16-F0; Mouse ovarian cancer cell line ID8 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00891 Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma. . . . Down regulation Driver Suppressor Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 106 tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 106 luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse. REF000064 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00069; CELL00555; CELL00584 HT-1080; A375; B16-F0; Mouse ovarian cancer cell line ID8 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01053 Hyperactive mutation of PI3K-AKT-mTOR signaling protects cancer cells from oxidative stress and ferroptotic death through SREBP1/SCD1-mediated lipogenesis, and combination of mTORC1 inhibition with ferroptosis induction shows therapeutic promise of preclinical models in Fibrosarcoma. . . . Up regulation Suppressor Suppressor For the in vivo xenograft mouse model, 17-b-estradiol 60-d release pellets (Innovative Research of America) were implanted subcutaneously into the left flank 7 d before tumor inoculation. GPX4 iKO BT474 cells were inoculated by injecting 5 x 106 cells in 50% Matrigel subcutaneously in the right flank of 6- to 8-wk-old female athymicnu/numice (Envigo). For PC-3 tumor models, male athymic nu/nu mice aged 5 to 6 wk were injected in the right flank with 5 x 106 PC-3 cells. REF000270 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00005; CELL00111; CELL00078; CELL00002; CELL00135; CELL00323; CELL00048; CELL00051; CELL00065; CELL00045; CELL00056; CELL00107; CELL00060 HT1080; MDA-MB-231; MDA-MB-453; BT474; MCF7; T47D; U87MG; HepG2; PC-3; DU145; A549; NCI-H1299; LN229; SK-MEL-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique01052 Hyperactive mutation of PI3K-AKT-mTOR signaling protects cancer cells from oxidative stress and ferroptotic death through SREBP1/SCD1-mediated lipogenesis, and combination of mTORC1 (RPTOR is a core component of mTORC1) inhibition with ferroptosis induction shows therapeutic promise of preclinical models in Fibrosarcoma. . . . Up regulation Suppressor Suppressor Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection). REF000270 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00005; CELL00111; CELL00078; CELL00002; CELL00135; CELL00323; CELL00048; CELL00051; CELL00065; CELL00045; CELL00056; CELL00107; CELL00060 HT1080; MDA-MB-231; MDA-MB-453; BT474; MCF7; T47D; U87MG; HepG2; PC-3; DU145; A549; NCI-H1299; LN229; SK-MEL-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique01297 MS4A15 regulation of anti-ferroptotic lipid reservoirs provides a key resistance mechanism that is distinct from antioxidant and lipid detoxification pathways. And Scd1 and Fads2 are counterregulated with Ms4a15 OE in Fibrosarcoma. . . . Up regulation Suppressor Suppressor . REF000549 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00143; CELL00002; CELL00005; CELL00057; CELL00195; CELL00049; CELL00045 HT1080; Calu-1; MCF-7; MDA-MB-231; HEK293T; H1975; HeLa; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell migration
unique00966 DO264, a selective inhibitor of the lyso- and ox-phosphatidylserine (PS) lipase ABHD12, enhances ferroptotic death caused by RSL3 in fibrosarcoma cells, an inhibitor of the lipid peroxidase GPX4. Inducer Down regulation . . Suppressor . . REF000151 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00227 HT1080; SU-DHL-5 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01043 Iron-dependent and competitive protein labeling by FIPC-1 was demonstrated in a quantitative chemoproteomic workflow that identified several saturable protein targets in fibrosarcoma cells, including P4HB and NT5DC2. Inducer Down regulation . . Suppressor . . REF000257 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00069 HT-1080; A375; AK210 Ferroptosis (hsa04216) Cell ferroptosis
unique01042 Iron-dependent and competitive protein labeling by FIPC-1 was demonstrated in a quantitative chemoproteomic workflow that identified several saturable protein targets in fibrosarcoma cells, including P4HB and NT5DC2. Inducer Down regulation . . Suppressor . . REF000257 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00069 HT-1080; A375; AK210 Ferroptosis (hsa04216) Cell ferroptosis
unique00028 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC- and -selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor . Down regulation . . Driver . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00035 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC- and -selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor . Down regulation . . Driver . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00031 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC- and -selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor . Down regulation . . Driver . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00036 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC- and -selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor . Down regulation . . Driver . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00029 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX, including NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor . Down regulation . . Driver . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00027 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a (PRKCA) and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor Down regulation . . Driver . . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00026 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a (PRKCA) and b-selective inhibitor Go-6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor Down regulation . . Driver . . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00034 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX, including NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor Down regulation . . Driver . . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00033 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX, including NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor Down regulation . . Driver . . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00030 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX, including NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor Down regulation . . Driver . . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00032 Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX, including NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death. Suppressor Down regulation . . Driver . . REF000071 ICD-11: 2B55 Rhabdomyosarcoma CELL00213; CELL00389; CELL00054; CELL00525; CELL00241; CELL00534; CELL00393; CELL00424 RD; RH18; RH30; RH36; RH41; T 174; TE 381.T; Kym-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01778 Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the GIC and suppressing stemness. BBR induces cell death in gastrointestinal cancer cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH. Inducer . Up regulation . . Driver Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 107 in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day. REF001007 ICD-11: 2B5B Gastrointestinal cancer CELL00562; CELL00280; CELL00561 HT29; TMK-1; CT26 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique01776 Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the GIC and suppressing stemness. BBR induces cell death in gastrointestinal cancer cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH. Inducer . Down regulation . . Suppressor Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 107 in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day. REF001007 ICD-11: 2B5B Gastrointestinal cancer CELL00562; CELL00280; CELL00561 HT29; TMK-1; CT26 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique00946 Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis. . . . Up regulation Suppressor Suppressor . REF000114 ICD-11: 2B5B Upper gastrointestinal adenocarcinoma CELL00119; CELL00114; CELL00327 OE33; MKN45; STKM2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00945 Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis. . . . Down regulation Driver Suppressor . REF000114 ICD-11: 2B5B Upper gastrointestinal adenocarcinoma CELL00119; CELL00114; CELL00327 OE33; MKN45; STKM2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01777 Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the gastrointestinal cancer and suppressing stemness. BBR induces cell death in GIC cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH. Inducer . Down regulation . . Suppressor Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 107 in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day. REF001007 ICD-11: 2B5B Gastrointestinal cancer CELL00562; CELL00280; CELL00561 HT29; TMK-1; CT26 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique00259 Cucurbitacin B caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. The study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer. Inducer . Down regulation . . Suppressor The animal experiment was performed in accordance with protocols approved by the Institutional Animal Care and Use Committee of Guangzhou Medical University. BALB/c nude mice (5 weeks old, female, Guangdong Medical Laboratory Animal Centre, China) were used for animal experiments. Approximately 4 million CNE1 cells were injected subcutaneously into the right flank of each mouse. Palpable solid tumours developed within a month after tumour cell inoculation, and mice were randomly allocated to four different groups (five mice /group) as follows: control (PBS) group, CuB treatment groups [0.5 mg/kg (low-dose) group and 1 mg/kg (high-dose) group] and gemcitabine (GEM, 25 mg/kg) group. Mice received intraperitoneal injections of PBS, CuB, and gemcitabine 3 times weekly. REF000348 ICD-11: 2B6B Nasopharyngeal cancer CELL00002; CELL00070; CELL00480; CELL00048; CELL00249; CELL00250 MCF-7; A2780; CNE1; HepG2; H157; HCT-8 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell migration; Cell invasion
unique00273 Cephalosporin antibiotics showed highly specific and selective anticancer activity on nasopharyngeal carcinoma CNE2 cells both in vitro and vivo with minimal toxicity. Pathway analyses indicate apoptotic and the ErbB-MAPK-p53 signaling pathways are significantly enriched. HMOX1 represents the top one ranked upregulated gene by COS and overlaps with 16 of 42 enriched apoptotic signaling pathways. Inhibition of HMOX1 significantly reduced the anticancer efficacy of cefotaxime in CNE2 cells. Inducer . Up regulation . . Driver/Suppressor 6-8 week old male balb/cnude micewere purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Nasopharyngeal carcinoma CNE2 cells were collected during logarithmic growth and rinsed with PBS twice and resuspended to a density of 1 x 107 cells/ml using fresh and cooled DMEM/F12 medium (free of FBS and antibiotics). Each mouse was inoculated subcutaneously with a 0.1 ml cell suspension on the right-side flank. Tumor-bearing mice were used for in vivo anticancer studies 8 days after inoculation when the average tumor volume reached ~200 mm3. REF000378 ICD-11: 2B6B Nasopharyngeal cancer CELL00045; CELL00518; CELL00048; CELL00087; CELL00124; CELL00481; CELL00043; CELL00002; CELL00036; CELL00401 A549; XWLC05; HepG2; HCT116; SGC7901; CNE2; U251; MCF7; K562; ECV304 Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01834 Lupeol significantly elevated AMPK phosphorylation, and reduced the levels of p-IB and nuclear NF-kB p65 (RELA). Lupeol exerted the anti-cancer impacts by inducing oxidative stress, ferroptosis and apoptosis, and suppressing inflammation via the AMPK/NF-kB pathway in nasopharyngeal carcinoma. Inducer Down regulation . . Suppressor . BALB/c nude mice (6-week-old) were purchased from Junke biology Co., Ltd (Nanjing, China). All mice were individually housed and had free access to food and water. Then, 58?F and CNE1 cells (5x106 cells in 200 l medium) were inoculated into right flank of mice. Mice were divided into 2 groups: sham group and 10 mg/kg lupeol group (5 mice per group). Specifically, mice of the 10 mg/kg lupeol group were intraperitoneally administrated with lupeol (10 mg/kg, every 3 days) referring to previous studies [Citation23,Citation24]. Mice in the sham group received an equivalent volume of PBS. At day 40 after lupeol treatment, mice were euthanized by cervical dislocation after anesthetizing with 3% isoflurane. The tumor volume and weight were recorded, respectively. Animal experiments were conducted following the approval of the Ethics Committee of Shenzhen Peoples Hospital (No. SYXK(YUE)2017-0174). REF000726 ICD-11: 2B6B Nasopharyngeal cancer . . Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00527 The current findings highlight that carnosic acid may re-sensitize cisplatin-resistant cells to cisplatin by inducing ferroptosis, which involves the inactivation of Nrf2/HO-1/xCT pathway. Hence, this research may support a promising therapeutic approach to overcome chemoresistance in Oral squamous cell carcinoma. Inducer . Down regulation . . Suppressor . REF000727 ICD-11: 2B6E.0 Oral squamous cell carcinoma . . Ferroptosis (hsa04216) Cell ferroptosis
unique00526 The current findings highlight that carnosic acid may re-sensitize cisplatin-resistant cells to cisplatin by inducing ferroptosis, which involves the inactivation of Nrf2/HO-1/xCT pathway. Hence, this research may support a promising therapeutic approach to overcome chemoresistance in Oral squamous cell carcinoma. Inducer . Down regulation . . Marker/Suppressor . REF000727 ICD-11: 2B6E.0 Oral squamous cell carcinoma . . Ferroptosis (hsa04216) Cell ferroptosis
unique01278 EZH2 inhibits the ferroptosis of tongue squamous cell carcinoma cells by inhibiting miR-125b-5p and enhancing SLC7A11. MiR-125b-5p regulates ferroptosis in TSCC cells by targeting SLC7A11. . . . Up regulation Suppressor Suppressor . REF000530 ICD-11: 2B6E Tongue squamous cell carcinoma CELL00300; CELL00537; CELL00159; CELL00219; CELL10100 Tca-8113; TSCCa; CAL-27; SCC-9; TEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01410 Low expression of miR-34c-3p in oral squamous cell carcinoma, negatively regulating SLC7A11 expression, promoting ferroptosis, and suppressing cell proliferation. . . . Down regulation Driver Suppressor . REF000656 ICD-11: 2B6E.0 Oral squamous cell carcinoma CELL00218; CELL00159; CELL00033 SCC-25; CAL-27; HOK Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01279 EZH2 inhibits the ferroptosis of tongue squamous cell carcinoma cells by inhibiting miR-125b-5p and enhancing SLC7A11. MiR-125b-5p regulates ferroptosis in TSCC cells by targeting SLC7A11. . . . Down regulation Driver Suppressor . REF000530 ICD-11: 2B6E Tongue squamous cell carcinoma CELL00300; CELL00537; CELL00159; CELL00219; CELL10100 Tca-8113; TSCCa; CAL-27; SCC-9; TEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01241 CircFNDC3B attenuated ferroptosis of Oral squamous cell carcinoma (OSCC) cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC. . . . Down regulation Driver Suppressor The tumorigenicity analysis was conducted in BALB/c nude mice (6-weeks-old, male). The mice were maintained at pathogen-free condition. The 5 x 106 CAL27 cells were treated with control shRNA or circFNDC3B shRNA and subcutaneously injected into the nude mice (N = 5). The mice were sacrificed after 30 days and the tumor volume was calculated using the formula of (length x width2)/2. REF000489 ICD-11: 2B6E.0 Oral squamous cell carcinoma CELL00159; CELL00217 CAL27; SCC15 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01240 CircFNDC3B attenuated ferroptosis of Oral squamous cell carcinoma (OSCC) cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC. . . . Up regulation Suppressor Suppressor The tumorigenicity analysis was conducted in BALB/c nude mice (6-weeks-old, male). The mice were maintained at pathogen-free condition. The 5 x 106 CAL27 cells were treated with control shRNA or circFNDC3B shRNA and subcutaneously injected into the nude mice (N = 5). The mice were sacrificed after 30 days and the tumor volume was calculated using the formula of (length x width2)/2. REF000489 ICD-11: 2B6E.0 Oral squamous cell carcinoma CELL00159; CELL00217 CAL27; SCC15 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00204 Modulation of GPX4 and HMOX1 by 5-aminolevulinic acid (5-ALA) induced ferroptosis in esophageal squamous cell carcinoma (ESCC). Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. Thus, 5-ALA could be a promising new therapeutic agent for ESCC. Inducer . Down regulation . . Suppressor KYSE30 cells were subcutaneously inoculated with 5 x 106 cells per site into both flanks on day 0. At 1 week after transplantation, tumor-bearing mice were randomly assigned to one of the following three groups: (1) saline as a control, (2) 10 mg/kg/day of 5-ALA, or (3) 30 mg/kg/day of 5-ALA. The treatment groups were orally administered 5-ALA once daily for 4 weeks, and the control group was orally administered saline during the same period. REF000268 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00184; CELL00186; CELL00114 KYSE30; KYSE510; MKN45 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00940 The correlation between DNAJB6 level and lymph node metastasis in esophageal squamous cell carcinoma (ESCC) patient was negative. Overexpressing DNAJB6a shows tumor-suppressive effects in vitro and in vivo. In addition, DNAJB6a overexpression was accompanied together with a remarkable reduction in the protein levels of GPX4 and phosphorylated AKT (p-AKT). . . . Down regulation Driver Suppressor Female BALB/c athymic nude mice (4 weeks of age) were obtained from the HFK Bioscience Co, Beijing. To generate murine subcutaneous tumors, 2 x 106 Eca109 cells and KYSE 150 cells in 100 ul PBS were injected subcutaneously on the left of the nude mices dorsal midline. The xenografts were measured every 4 days. REF000109 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00026; CELL00302; CELL00367; CELL00368 TE-1; Eca9706; Eca109; KYSE150; KYSE450 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01382 CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathwaysviamiR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11. . . . Up regulation Suppressor Suppressor BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 106) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. REF000629 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00187; CELL10061 EC9706; KYSE70; normal human esophageal epithelial cells (HEEC) Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell invasion
unique01574 CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. GPX4 protein levels were increased by silencing of circBCAR3. And circBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p. . . . Down regulation Driver Suppressor Nude mice of both sexes (age: 6-8 weeks, weight: 22-25 g) were purchased from HUNAN SJA LABRATORY ANIMAL CO., LTD (Hunan, China). The EC109 cells stably expressing sh-circBCAR3 or sh-nc were established by infection with corresponding lentivirus vectors. 1 x 106 mL-1 (100 uL) cells were subcutaneously inoculated into the nude mice. The tumor volumes had been measured from day 5 to day 25. On day 25, the xenograft tumors were removed surgically, and the tumor weight was detected. REF000781 ICD-11: 2B70 Esophageal cancer CELL00302 EC109 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01646 CARS1 significantly inhibited cell proliferation, and the ability of migration and invasion promoted the relative level of MDA and ROS and decreased GPX4 expression level in two esophageal squamous cell carcinoma(ESCC) cell lines. . . . Down regulation Driver Suppressor . REF000854 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00184; CELL00185 KYSE-30; KYSE-410 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01573 CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. GPX4 protein levels were increased by silencing of circBCAR3. And circBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p. . . . Up regulation Suppressor Suppressor Nude mice of both sexes (age: 6-8 weeks, weight: 22-25 g) were purchased from HUNAN SJA LABRATORY ANIMAL CO., LTD (Hunan, China). The EC109 cells stably expressing sh-circBCAR3 or sh-nc were established by infection with corresponding lentivirus vectors. 1 x 106 mL-1 (100 uL) cells were subcutaneously inoculated into the nude mice. The tumor volumes had been measured from day 5 to day 25. On day 25, the xenograft tumors were removed surgically, and the tumor weight was detected. REF000781 ICD-11: 2B70 Esophageal cancer CELL00302 EC109 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01381 CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathwaysvia miR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11. . . . Down regulation Driver Suppressor BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 106) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. REF000629 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00187; CELL10061 EC9706; KYSE70; normal human esophageal epithelial cells (HEEC) Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell invasion
unique01584 OIP5-AS1 inhibition significantly inhibited Oesophageal cancer (EC) cell viability and proliferation, induced ferroptosis, and downregulated GPX4 levels, while GPX4 reversed these effects. . . . Up regulation Suppressor Suppressor . REF000788 ICD-11: 2B70 Oesophageal carcinoma CELL00302; CELL00282; CELL00228; CELL00259; CELL10043 Eca109; TE-13; TE-1; TTN; normal oesophageal epithelial cell line HEEC Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01380 CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathwaysviamiR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11. . . . Up regulation Suppressor Suppressor BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 106) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. REF000629 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00187; CELL10061 EC9706; KYSE70; normal human esophageal epithelial cells (HEEC) Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell invasion
unique01572 CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. GPX4 protein levels were increased by silencing of circBCAR3. And circBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p. . . . Down regulation Driver Suppressor Nude mice of both sexes (age: 6-8 weeks, weight: 22-25 g) were purchased from HUNAN SJA LABRATORY ANIMAL CO., LTD (Hunan, China). The EC109 cells stably expressing sh-circBCAR3 or sh-nc were established by infection with corresponding lentivirus vectors. 1 x 106 mL-1 (100 uL) cells were subcutaneously inoculated into the nude mice. The tumor volumes had been measured from day 5 to day 25. On day 25, the xenograft tumors were removed surgically, and the tumor weight was detected. REF000781 ICD-11: 2B70 Esophageal cancer CELL00302 EC109 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00205 Modulation of GPX4 and HMOX1 by 5-aminolevulinic acid (5-ALA) induced ferroptosis in esophageal squamous cell carcinoma (ESCC). Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. Thus, 5-ALA could be a promising new therapeutic agent for ESCC. Inducer . Down regulation . . Driver/Suppressor KYSE30 cells were subcutaneously inoculated with 5 x 106 cells per site into both flanks on day 0. At 1 week after transplantation, tumor-bearing mice were randomly assigned to one of the following three groups: (1) saline as a control, (2) 10 mg/kg/day of 5-ALA, or (3) 30 mg/kg/day of 5-ALA. The treatment groups were orally administered 5-ALA once daily for 4 weeks, and the control group was orally administered saline during the same period. REF000268 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00184; CELL00186; CELL00114 KYSE30; KYSE510; MKN45 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00642 In summary, allicin may induce cell death in esophageal squamous cell carcinoma (ESCC) cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Furthermore, ATG5 and ATG7 expression increased in tumors after allicin treatment. In contrast, NCOA4 expression increased, but the protein level of FTH1 and TfR1 decreased in tumors after allicin treatment. Inducer . Up regulation . . Driver All mice were housed in a specific pathogen-free environment under a standard 12 h light-dark cycle at 25 and had ad libitum access to food and water. Approximately 4 x 106 KYSE510 cells in 100 uL of normal saline were subcutaneously injected into the right flank of mice (n = 20 in total). All mice were allocated to a control or 10 mg/kg allicin group (n = 10 per group), as previously described (Suddek 2014). The mice were orally administered allicin or normal saline once daily for 28 days. REF000874 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00186; CELL00268 TE-1; KYSE-510; Het-1A mTOR signaling pathway (hsa04150); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01394 ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11. . . . Down regulation Driver Suppressor . REF000641 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00228; CELL00302; CELL00268 Ec9706; TE-1; EC109; Het-1A Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique01396 ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11. . . . Up regulation Suppressor Suppressor . REF000641 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00228; CELL00302; CELL00268 Ec9706; TE-1; EC109; Het-1A Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique01392 ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11. . . . Down regulation Driver Suppressor . REF000641 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00228; CELL00302; CELL00268 Ec9706; TE-1; EC109; Het-1A Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique01395 ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, 3SLC3A2, and SLC7A11. . . . Down regulation Driver Suppressor . REF000641 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00228; CELL00302; CELL00268 Ec9706; TE-1; EC109; Het-1A Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique01379 CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathwaysviamiR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11. . . . Up regulation Suppressor Suppressor BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 106) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. REF000629 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00187; CELL10061 EC9706; KYSE70; normal human esophageal epithelial cells (HEEC) Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell invasion
unique01378 CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathways via miR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11. . . . Down regulation Driver Suppressor BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 106) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. REF000629 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00187; CELL10061 EC9706; KYSE70; normal human esophageal epithelial cells (HEEC) Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell invasion
unique01397 ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11. . . . Up regulation Suppressor Suppressor . REF000641 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00228; CELL00302; CELL00268 Ec9706; TE-1; EC109; Het-1A Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique01648 Downregulation of BBOX1-AS1 inhibits cell proliferation, and metastasis accelerates cell apoptosis and ferroptosis in esophageal squamous cell cancer by upregulating miR-513a-3p to reduce SLC7A11 expression. These findings may provide novel insights into the diagnosis and treatment of ESCC. . . . Down regulation Driver Suppressor . REF000856 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL10012 Esophageal squamous cell cancer tissues Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01393 ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11. . . . Down regulation Driver Suppressor . REF000641 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00228; CELL00302; CELL00268 Ec9706; TE-1; EC109; Het-1A Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique01647 Downregulation of BBOX1-AS1 inhibits cell proliferation, and metastasis accelerates cell apoptosis and ferroptosis in esophageal squamous cell cancer by upregulating miR-513a-3p to reduce SLC7A11 expression. These findings may provide novel insights into the diagnosis and treatment of ESCC. . . . Up regulation Suppressor Suppressor . REF000856 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL10012 Esophageal squamous cell cancer tissues Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01377 CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathwaysviamiR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11. . . . Up regulation Suppressor Suppressor BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 106) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. REF000629 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00026; CELL00187; CELL10061 EC9706; KYSE70; normal human esophageal epithelial cells (HEEC) Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell invasion
unique00641 In summary, allicin may induce cell death in esophageal squamous cell carcinoma (ESCC) cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Furthermore, ATG5 and ATG7 expression increased in tumors after allicin treatment. In contrast, NCOA4 expression increased, but the protein level of FTH1 and TfR1 decreased in tumors after allicin treatment. Inducer . . . Driver . All mice were housed in a specific pathogen-free environment under a standard 12 h light-dark cycle at 25 and had ad libitum access to food and water. Approximately 4 x 106 KYSE510 cells in 100 uL of normal saline were subcutaneously injected into the right flank of mice (n = 20 in total). All mice were allocated to a control or 10 mg/kg allicin group (n = 10 per group), as previously described (Suddek 2014). The mice were orally administered allicin or normal saline once daily for 28 days. REF000874 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00186; CELL00268 TE-1; KYSE-510; Het-1A mTOR signaling pathway (hsa04150); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00639 In summary, allicin may induce cell death in esophageal squamous cell carcinoma (ESCC) cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Furthermore, ATG5 and ATG7 expression increased in tumors after allicin treatment. In contrast, NCOA4 expression increased, but the protein level of FTH1 and TfR1 decreased in tumors after allicin treatment. Inducer Down regulation . . Suppressor . All mice were housed in a specific pathogen-free environment under a standard 12 h light-dark cycle at 25 and had ad libitum access to food and water. Approximately 4 x 106 KYSE510 cells in 100 uL of normal saline were subcutaneously injected into the right flank of mice (n = 20 in total). All mice were allocated to a control or 10 mg/kg allicin group (n = 10 per group), as previously described (Suddek 2014). The mice were orally administered allicin or normal saline once daily for 28 days. REF000874 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00186; CELL00268 TE-1; KYSE-510; Het-1A mTOR signaling pathway (hsa04150); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00640 In summary, allicin may induce cell death in esophageal squamous cell carcinoma (ESCC) cells by activating AMPK/mTOR-mediated autophagy and ferroptosis. Furthermore, ATG5 and ATG7 expression increased in tumors after allicin treatment. In contrast, NCOA4 expression increased, but the protein level of FTH1 and TfR1 decreased in tumors after allicin treatment. Inducer . . . Driver . All mice were housed in a specific pathogen-free environment under a standard 12 h light-dark cycle at 25 and had ad libitum access to food and water. Approximately 4 x 106 KYSE510 cells in 100 uL of normal saline were subcutaneously injected into the right flank of mice (n = 20 in total). All mice were allocated to a control or 10 mg/kg allicin group (n = 10 per group), as previously described (Suddek 2014). The mice were orally administered allicin or normal saline once daily for 28 days. REF000874 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00186; CELL00268 TE-1; KYSE-510; Het-1A mTOR signaling pathway (hsa04150); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01616 The study demonstrates that eprenetapopt targets cancer cells through GSH depletion and inhibiting cysteine desulfurase activity of NFS1, leading to iron-dependent, nonapoptotic ferroptosis. The combination of eprenetapopt with dietary serine and glycine restriction synergizes to inhibit esophageal xenograft tumor growth. Inducer Up regulation . . Driver . For FLO-1 LM cell line xenografts, 5 x 106 cells suspended in 100 ul of 1:1 PBS and Matrigel (BD Biosciences) were subcutaneously injected into the right flank of ~6 week-old female nonobese diabeticsevere combined immunodeficient interleukin-2RKO (NSG) mice. PDXs were established and implanted into a dorsal intramuscular pocket of NSG mice as previously described. Mice were randomized to SG deplete or control chow ad libitum (AIN93G rodent diet, Specialty Feeds, Australia) and dosed with eprenetapopt (100 mg/kg) or 0.9% saline, intraperitoneally injected daily, once tumors reached 100 mm3. Tumor volume was assessed blinded to treatment group with caliper measurements every 3 to 4 days and calculated using the formula (length x weight2)/2. Metastatic spread was determined by bioluminescence imaging as previously described involving weekly monitoring using the Xenogen IVIS 100 Imaging System (Caliper Life Science). At experimental end point (tumor volume > 1400 mm3), the whole mouse and its organs were imaged to determine the extent and distribution of metastases. Tumors were weighed and tumor growth inhibition was calculated with the formula [1 - (Tf- Ti)/mean(Cf - Ci)] x 100, where Tf, Ti, Cf, and Ci represent final (f) and initial (i) tumor volume of drug treated (T) and control (C) animals, respectively. REF000829 ICD-11: 2B70 Esophageal cancer CELL00056; CELL00395; CELL00402; CELL00057 H1299; OACM5.1; FLO-1; 293T Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00925 Overexpression and knockdown of PLIN2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. PLIN2 modulated Ferroptosis pathway through regulating transcription factors-PRDM11 and IPO7:ACSL3 was a critical gene involved in abnormal lipid metabolism, ALOX15 facilitated apoptosis and necrosis. . . . Down regulation Suppressor Driver/Suppressor SGC7901 cell line transfected with OvPLIN2, ShPLIN2 and Control were injected subcutaneously into the nude mice (BALB/c nu/nu, female, 5 weeks old, Beijing Huafukang Biotechnology Co. Ltd. China) which were anaesthetized with 1% Sodium pentobarbital. The long diameter a and short diameter b of mouse tumor and the weights were measured every 4-5 days, and the relative tumor volumes (RTV) were calculated according to formula 0.5 x a x b x b. REF000092 ICD-11: 2B72 Gastric cancer CELL00124; CELL00290 SGC7901; MGC803 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01511 Schematic diagram showing that HIF-1 induces lncRNA-CBSLR to recruit YTHDF2 protein and CBS mRNA to form CBSLR/ YTHDF2/CBS complex, which in turn decreases CBS mRNA stability in an m6A dependent manner. The decreased CBS expression reduced methylation of ACSL4 protein, thus, the protein is degraded via the ubiquitination-proteasome pathway. Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. . . . Down regulation Suppressor Driver Female non-obese diabetic severe combined immune-deficient mice at 5 weeks of age were divided into indicated groups and injected subcutaneously at either side of flank area with indicated cell lines (1 x 106 cells) suspended in 0.1 ml phosphate-buffered saline (PBS). Tumor sizes in all groups were measured every 3 days using Vernier calipers and calculated using the following formula: (length x width2)/2. For the xenograft Cisplatin treatment assay, day 0 was designed when tumors reached around 50 mm3 in volume. DDP 7 mg/kg or carrier (PBS, 100 uL)) was injected intraperitoneally 1 time per week. 21 days after treatment, all mice were sacrificed and tumors were harvested and weighed. Representative images were presented, and all experiments were repeated at least 3 times. REF000731 ICD-11: 2B72 Gastric cancer CELL00114; CELL00193 MKN45; MKN28 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01512 Schematic diagram showing that HIF-1 induces lncRNA-CBSLR to recruit YTHDF2 protein and CBS mRNA to form CBSLR/ YTHDF2/CBS complex, which in turn decreases CBS mRNA stability in an m6A dependent manner. The decreased CBS expression reduced methylation of ACSL4 protein, thus, the protein is degraded via the ubiquitination-proteasome pathway. Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. . . . Up regulation Driver Driver Female non-obese diabetic severe combined immune-deficient mice at 5 weeks of age were divided into indicated groups and injected subcutaneously at either side of flank area with indicated cell lines (1 x 106 cells) suspended in 0.1 ml phosphate-buffered saline (PBS). Tumor sizes in all groups were measured every 3 days using Vernier calipers and calculated using the following formula: (length x width2)/2. For the xenograft Cisplatin treatment assay, day 0 was designed when tumors reached around 50 mm3 in volume. DDP 7 mg/kg or carrier (PBS, 100 uL)) was injected intraperitoneally 1 time per week. 21 days after treatment, all mice were sacrificed and tumors were harvested and weighed. Representative images were presented, and all experiments were repeated at least 3 times. REF000731 ICD-11: 2B72 Gastric cancer CELL00114; CELL00193 MKN45; MKN28 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00924 Overexpression and knockdown of PLIN2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. PLIN2 modulated Ferroptosis pathway through regulating transcription factors-PRDM11 and IPO7:ACSL3 was a critical gene involved in abnormal lipid metabolism, ALOX15 facilitated apoptosis and necrosis. . . . Down regulation Suppressor Driver SGC7901 cell line transfected with OvPLIN2, ShPLIN2 and Control were injected subcutaneously into the nude mice (BALB/c nu/nu, female, 5 weeks old, Beijing Huafukang Biotechnology Co. Ltd. China) which were anaesthetized with 1% Sodium pentobarbital. The long diameter a and short diameter b of mouse tumor and the weights were measured every 4-5 days, and the relative tumor volumes (RTV) were calculated according to formula 0.5 x a x b x b. REF000092 ICD-11: 2B72 Gastric cancer CELL00124; CELL00290 SGC7901; MGC803 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00154 Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. Inducer . Up regulation . . Marker/Driver All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 106 BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points. REF000207 ICD-11: 2B72 Gastric cancer CELL00261; CELL00023 BGC-823; NCI-H87 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01195 CPEB1 overexpression reduced the expression of twist1, an inhibitor of activating transcription factor 4 (ATF4), thereby activating the ATF4/ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 (CHAC1) pathway (CHAC1, a molecule known to induce GSH degradation). Furthermore, re-expression of twist1 in gastric cancer cells impaired the effects of CPEB1 overexpression in presence of erastin. . . . Up regulation Driver Marker/Driver Healthy male nude mice for 5 weeks were randomly divided into four groups, namely: A: Lv-NC + Vehicle group, B: Lv-NC + Erastin group, C: Lv-exCPEB1 + Vehicle group, and D: Lv-exCPEB1 + Erastin group. The living environment of nude mice in each group was 12 h light and 12 h dark, the temperature was 22 ± 1, the humidity was 45-55%. The model was established 1 week after adaptive feeding. GC cells (1 x 106) with stable overexpression of CPEB1 at the logarithmic growth stage were selected and injected subcutaneously in nude mice. When the tumor volume reached 100 mm3, nude mice in groups B and D were injected intraperitoneally with Erastin (30 mg/kg) twice a day (morning and night, respectively), and the tumor tissue diameter and volume were measured and calculated every 3 days after administration. REF000444 ICD-11: 2B72 Gastric cancer CELL00071; CELL00006; CELL00011; CELL00174; CELL00322 AGS; SNU-1; Hs-746T; HGC-27; GES-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01784 For the first time, our results have demonstrated that Polyphyllin I exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosisviaregulating NRF2/FTH1 pathway. Inducer . Down regulation . . Marker/Suppressor A subcutaneous gastric tumor model was established by subcutaneously injecting 1 x 106 AGS cells or 2 x 106 MKN-45 cells near the right axilla of mice. Seven days after tumor cell inoculation, mice received daily i. p. Injection of PPI (3 mg/kg, dissolved in 1% DMSO + 5% PEG300 + 5% Tween 80 + 89% deionized water), as described previously, or the control solution with the same solvent. Mice were weighed at day 15, while tumor volumes were measured every 3 days and calculated using a formula: length x width2/2. REF001013 ICD-11: 2B72 Gastric cancer CELL00114; CELL00071 MKN-45; AGS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00761 We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1 in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. Inducer . Up regulation . . Marker The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software. REF000984 ICD-11: 2B72 Gastric cancer CELL00208; CELL00192; CELL00114; CELL00174; CELL00257 NUGC-3; MKN-1; MKN-45; HGC-27; NUGC-4 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00294 Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM. Suppressor . Up regulation . . Suppressor . REF000413 ICD-11: 2B72 Gastric cancer CELL00254; CELL00257 MKN74; NUGC4 Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00628 Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in gastric cancer cells. This study revealed the molecular biological mechanism by which Atranorin@SPION inhibit the in vitro and in vivo activity of GCSCs, that is, Atranorin@SPION reduced the expression of members of the Xc-/GPX4 axis and reduced their mRNA 5-hydroxymethylcytidine modification, finally induced ferroptosis of GCSCs. Inducer . Down regulation . . Suppressor NOD-scid mice (NOD.CB17-Prkdcscid/NcrCrl) aged 6-7 weeks and weighing 20-22 g were used in the experiment. The animal study was performed at the Shanghai University of Traditional Chinese Medicine with approval from the Institutional Animal Care and Use Committee in accordance with the institutional guidelines. All mice were randomly divided into two groups, and each group consisted of four mice. In experimental group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul Atranorin@SPION (10 mg/kg) every 2 days. In control group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul SPION (10 mg/kg) alone every 2 days. After 2 months, the mice were sacrificed, and their tumors were excised. REF000861 ICD-11: 2B72 Gastric cancer CELL10014 Gastric cancer tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00502 6-Thioguanine was identified as a potential ferroptosis inducer in gastric cancer cells for the first time. It could inactivate system xc, block the generation of GSH, down-regulate the expression of GPX4, increase the level of Lipid ROS, and finally trigger the Fe-2+-mediated ferroptosis in MGC-803 and AGS cell lines. Inducer . Down regulation . . Suppressor Female BALB/c nude mice (6-7 weeks, 17-18 g) were purchased from Hunan Slack Scene of Laboratory Animal Co., Ltd. and used to establish the xenograft mouse model with 5 x 106 exponentially growing MGC-803 cells inoculated subcutaneously into the right forelimb for each mouse. Once the volume of tumors reached 100 mm3, the mice were divided into 3 groups: solvent control; 6-TG (10 mg/kg/day); 6-TG (10 mg/kg/day) + Fer-1(50 mg/kg/day). REF000682 ICD-11: 2B72 Gastric cancer CELL00290; CELL00071 MGC-803; AGS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00574 The pro-ferroptotic role of XN4 in gastric cancer (GC) might enable it to become a promising drug for GC treatment in the future despite the need for extensive research. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown. Inducer . Down regulation . . Suppressor . REF000800 ICD-11: 2B72 Gastric cancer CELL00124; CELL00261; CELL00322 SGC-7901; BGC-823; GES-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00324 (6R,6aR,9S,11bS,14R)-4,4-Dimethyl-8-methylene-7,11,12-trioxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl valinate (a2), a new JDA derivative, inhibited the growth of gastric cancer cells. Importantly, compounda2decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity ofa2. Furthermore, a2caused ferrous iron accumulation through the autophagy pathway, prevention of which rescueda2induced ferrous iron elevation and cell growth inhibition. Inducer . Down regulation . . Suppressor Male nude mice (ages 6-8 weeks) used in the studies were purchased from Hunan SJA Laboratory Animal Co. (Changsha, China). Male nude mice were subcutaneously injected with MGC-803cells into the right flank of mouse. Once the tumor volume reached 100-200 mm3, mice were randomly divided into 5 groups (6 mice/group) and administered with saline,a2(5, 10, and 20 mg/kg), or 5-fluorouracil (5-FU, 15mg/kg) once a day for 21 daysviatail vein injection. REF000447 ICD-11: 2B72 Gastric cancer CELL00174; CELL00290; CELL00261; CELL00071; CELL00322 HGC-27; MGC-803; BGC-823; AGS; GES1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique00101 Actinidia chinensis Planch (ACP) increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype. Inducer . Down regulation . . Suppressor Wild type AB strain of zebrafish (Danio rerio) was obtained from Southern Medical University. The HGC-27 cells labeled with EGFP were resuspended in PBS in the concentration of 5*107/ml. 10 nl cell suspension containing approximately 300 cells were loaded into capillary needles and injected into the abdominal perivitelline space of zebrafish embryos by a nanoliter injector (Narishige, Tokyo, Japan). After injection, the tumor-bearing embryos were transferred into a 24-well plate and acclimated in embryo water at 35 for 24 h and then incubated at 0, 90, 180 mg/ml ACP decoction for 48 h. REF000154 ICD-11: 2B72 Gastric cancer CELL00174 HGC-27 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration
unique00758 We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer (GC) cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. Inducer . Down regulation . . Suppressor The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software. REF000984 ICD-11: 2B72 Gastric cancer CELL00208; CELL00192; CELL00114; CELL00174; CELL00257 NUGC-3; MKN-1; MKN-45; HGC-27; NUGC-4 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00851 Silencing CDO1 inhibited erastin-induced ferroptosis in gastric cancer cells both in vitro and in vivo. Mechanistically, c-Myb (MYB) transcriptionally regulated CDO1, and inhibition of CDO1 expression upregulated GPX4 expression. . . . Down regulation Driver Suppressor 1 x 106 BGC823 control or CDO1 short hairpin (sh)RNA treated cells in 150 ul PBS were injected subcutaneously right of the dorsal midline in athymic nude mice. Once the tumors reached 80 to 100 mm3 at day 10, mice were allocated randomly into groups of five and treated with erastin (30 mg/kg intraperitoneally, twice every other day). REF000031 ICD-11: 2B72 Gastric cancer CELL00071; CELL00261; CELL00114; CELL00124; CELL00290 AGS; BGC823; MKN45; SGC7901; MGC803 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00850 Silencing CDO1 inhibited erastin-induced ferroptosis in gastric cancer cells both in vitro and in vivo. Mechanistically, c-Myb transcriptionally regulated CDO1, and inhibition of CDO1 expression upregulated GPX4 expression. . . . Down regulation Driver Suppressor 1 x 106 BGC823 control or CDO1 short hairpin (sh)RNA treated cells in 150 ul PBS were injected subcutaneously right of the dorsal midline in athymic nude mice. Once the tumors reached 80 to 100 mm3 at day 10, mice were allocated randomly into groups of five and treated with erastin (30 mg/kg intraperitoneally, twice every other day). REF000031 ICD-11: 2B72 Gastric cancer CELL00071; CELL00261; CELL00114; CELL00124; CELL00290 AGS; BGC823; MKN45; SGC7901; MGC803 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01252 SIRT6 inhibition led to the inactivation of the Keap1/Nrf2 signalling pathway and downregulation of GPX4. The overexpression of GPX4 or activation of Keap1/Nrf2 reverses the effects of the downregulation of SIRT6 on sorafenib-induced ferroptosis. Thus, targeting the SIRT6/Keap1/Nrf2/GPX4 signalling pathway may be a potential strategy for overcoming sorafenib resistance in gastric cancer. . . . Up regulation Suppressor Suppressor . REF000502 ICD-11: 2B72 Gastric cancer CELL00023; CELL00174 NCIN87; HGC-27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Pathways in cancer (hsa05200) Cell ferroptosis
unique00293 Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM. Suppressor . Up regulation . . Driver/Suppressor . REF000413 ICD-11: 2B72 Gastric cancer CELL00254; CELL00257 MKN74; NUGC4 Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00760 We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. Inducer . Up regulation . . Driver The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software. REF000984 ICD-11: 2B72 Gastric cancer CELL00208; CELL00192; CELL00114; CELL00174; CELL00257 NUGC-3; MKN-1; MKN-45; HGC-27; NUGC-4 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00572 The pro-ferroptotic role of XN4 in gastric cancer (GC) might enable it to become a promising drug for GC treatment in the future despite the need for extensive research. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown. Inducer . Up regulation . . Driver . REF000800 ICD-11: 2B72 Gastric cancer CELL00124; CELL00261; CELL00322 SGC-7901; BGC-823; GES-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01783 For the first time, our results have demonstrated that Polyphyllin I exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosisviaregulating NRF2/FTH1 pathway. Inducer . Down regulation . . Marker/Suppressor A subcutaneous gastric tumor model was established by subcutaneously injecting 1 x 106 AGS cells or 2 x 106 MKN-45 cells near the right axilla of mice. Seven days after tumor cell inoculation, mice received daily i. p. Injection of PPI (3 mg/kg, dissolved in 1% DMSO + 5% PEG300 + 5% Tween 80 + 89% deionized water), as described previously, or the control solution with the same solvent. Mice were weighed at day 15, while tumor volumes were measured every 3 days and calculated using a formula: length x width2/2. REF001013 ICD-11: 2B72 Gastric cancer CELL00114; CELL00071 MKN-45; AGS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00153 Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. Inducer . Up regulation . . Marker All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 106 BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points. REF000207 ICD-11: 2B72 Gastric cancer CELL00261; CELL00023 BGC-823; NCI-H87 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00573 The pro-ferroptotic role of XN4 in gastric cancer (GC) might enable it to become a promising drug for GC treatment in the future despite the need for extensive research. Moreover, GPX4 levels decreased, but NOX4 and ferroptosis-related protein PTGS2 levels increased in GC cells following XN4 treatment, which was nullified by NOX4 knockdown. Inducer . Up regulation . . Marker . REF000800 ICD-11: 2B72 Gastric cancer CELL00124; CELL00261; CELL00322 SGC-7901; BGC-823; GES-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00629 Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in gastric cancer cells. This study revealed the molecular biological mechanism by which Atranorin@SPION inhibit the in vitro and in vivo activity of GCSCs, that is, Atranorin@SPION reduced the expression of members of the Xc-/GPX4 axis and reduced their mRNA 5-hydroxymethylcytidine modification, finally induced ferroptosis of GCSCs. Inducer . Down regulation . . Suppressor NOD-scid mice (NOD.CB17-Prkdcscid/NcrCrl) aged 6-7 weeks and weighing 20-22 g were used in the experiment. The animal study was performed at the Shanghai University of Traditional Chinese Medicine with approval from the Institutional Animal Care and Use Committee in accordance with the institutional guidelines. All mice were randomly divided into two groups, and each group consisted of four mice. In experimental group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul Atranorin@SPION (10 mg/kg) every 2 days. In control group, approximately 1 x 105 GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul SPION (10 mg/kg) alone every 2 days. After 2 months, the mice were sacrificed, and their tumors were excised. REF000861 ICD-11: 2B72 Gastric cancer CELL10014 Gastric cancer tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00102 Actinidia chinensis Planch (ACP) increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype. Inducer . Down regulation . . Suppressor Wild type AB strain of zebrafish (Danio rerio) was obtained from Southern Medical University. The HGC-27 cells labeled with EGFP were resuspended in PBS in the concentration of 5*107/ml. 10 nl cell suspension containing approximately 300 cells were loaded into capillary needles and injected into the abdominal perivitelline space of zebrafish embryos by a nanoliter injector (Narishige, Tokyo, Japan). After injection, the tumor-bearing embryos were transferred into a 24-well plate and acclimated in embryo water at 35 for 24 h and then incubated at 0, 90, 180 mg/ml ACP decoction for 48 h. REF000154 ICD-11: 2B72 Gastric cancer CELL00174 HGC-27 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration
unique01693 Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells. . . . Up regulation Suppressor Suppressor Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 106 ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks. REF000912 ICD-11: 2B72 Gastric cancer CELL00322; CELL00124; CELL00174; CELL00071; CELL00290; CELL00114 GES-1; SGC7901; HGC27; AGS; MGC803; MKN45 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01583 HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability of SLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells. . . . Up regulation Suppressor Suppressor For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle. REF000786 ICD-11: 2B72 Gastric cancer CELL00071; CELL00290 AGS; MGC-803 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00971 GDF15 knockdown promotes erastin-induced ferroptosis in gastric cancer cell MGC803 by attenuating the expression of SLC7A11 and the function of system Xc-. . . . Up regulation Suppressor Suppressor . REF000155 ICD-11: 2B72 Gastric cancer CELL00290 MGC803 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01694 Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells. . . . Up regulation Suppressor Suppressor Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 106 ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks. REF000912 ICD-11: 2B72 Gastric cancer CELL00322; CELL00124; CELL00174; CELL00071; CELL00290; CELL00114 GES-1; SGC7901; HGC27; AGS; MGC803; MKN45 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01183 MiR-375 reduced the stemness of gastric cancer cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis. . . . Down regulation Driver Suppressor Four- to eight-week-old female BALB/c nude mice were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). For the tumor-limiting dilution assay, 1 x 107, 5 x 106, and 2.5 x 106 of LV3-miR-375 cells, LV3-SLC7A11 cells, LV3-shSLC7A11 cells, LV3-miR-375-SLC7A11 cells, and LV3-NC cells (BGC-823 and SGC-7901) were subcutaneously implanted into the underarm of mice. Fifteen days later, all mice were euthanized and tumor tissues were collected and weighed. For metastasis experiment, mouse models were established by intravenous injection of cells. Three mice per group were injected with 2 x 106 cells in 200 uL RPMI-1640 serum-free media. Six weeks after injection, mice were sacrificed for collecting lung tissues. REF000422 ICD-11: 2B72 Gastric cancer CELL00124; CELL00261; CELL00322 SGC-7901; BGC-823; GES-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell stemness
unique01638 circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis. . . . Down regulation Driver Suppressor . REF000850 ICD-11: 2B72 Gastric cancer CELL00114; CELL00071; CELL00011; CELL00023; CELL00174 MKN-45; AGS; Hs-746T; N87; HGC-27 Ferroptosis (hsa04216) Cell ferroptosis
unique01582 HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability ofSLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells. . . . Up regulation Suppressor Suppressor For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle. REF000786 ICD-11: 2B72 Gastric cancer CELL00071; CELL00290 AGS; MGC-803 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01637 circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis. . . . Up regulation Suppressor Suppressor . REF000850 ICD-11: 2B72 Gastric cancer CELL00114; CELL00071; CELL00011; CELL00023; CELL00174 MKN-45; AGS; Hs-746T; N87; HGC-27 Ferroptosis (hsa04216) Cell ferroptosis
unique00759 We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. Inducer . Up regulation . . Driver The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software. REF000984 ICD-11: 2B72 Gastric cancer CELL00208; CELL00192; CELL00114; CELL00174; CELL00257 NUGC-3; MKN-1; MKN-45; HGC-27; NUGC-4 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01450 BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in gastric cancer by affecting VDAC3 ubiquitination. . . . Down regulation Driver Suppressor Four- to six-week-old nude mice (BALB/c) were purchased from Jiangsu Jicui Yaokang Biotechnology Co. Ltd. (Nanjing, China) and then randomly divided into 3 groups (n = 5 per group). PO-BDNF-AS-HGC-27 cells, PONC-BDNF-AS-HGC-27 cells, or PO-BDNF-AS + PO-FBXW7-HGC-27 cells (5 x 106) were suspended in 100 ul DMEM and subcutaneously injected into the flanks of the mice in each group. After 10 days, we measured the tumor size every week using digital Vernier calipers and calculated the tumor volume based on the formula: volume = 1/2 x (width2 x length). On the 30th day or when the tumor became larger than 1.5 cm in diameter, the mice were sacrificed. Subsequently, the subcutaneous graft tumors were removed for further experiments. For the intraabdominal tumor model, we randomly divided the mice into two groups (n = 6 per group). PO-BDNF-AS-HGC-27 cells or PONC-BDNF-AS-HGC-27 cells (8 x 106) were suspended in 150 uL DMEM and intraperitoneally injected into the mice in each group (weight, approximately 18.0-19.0 g). Five weeks after injection, the mice were euthanized and necropsied to assess abdominal tumor burden and tumor location. Finally, we detected the mRNA and protein expression levels of relevant genes in the tumor tissues by RT-PCR and western blotting assays. REF000684 ICD-11: 2B72 Gastric cancer CELL00071; CELL00174; CELL00261; CELL00290; CELL00114; CELL00322 AGS; HGC-27; BGC-823; MGC-803; MKN-45; GES-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01449 BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in gastric cancer by affecting VDAC3 ubiquitination. . . . Up regulation Suppressor Suppressor Four- to six-week-old nude mice (BALB/c) were purchased from Jiangsu Jicui Yaokang Biotechnology Co. Ltd. (Nanjing, China) and then randomly divided into 3 groups (n = 5 per group). PO-BDNF-AS-HGC-27 cells, PONC-BDNF-AS-HGC-27 cells, or PO-BDNF-AS + PO-FBXW7-HGC-27 cells (5 x 106) were suspended in 100 ul DMEM and subcutaneously injected into the flanks of the mice in each group. After 10 days, we measured the tumor size every week using digital Vernier calipers and calculated the tumor volume based on the formula: volume = 1/2 x (width2 x length). On the 30th day or when the tumor became larger than 1.5 cm in diameter, the mice were sacrificed. Subsequently, the subcutaneous graft tumors were removed for further experiments. For the intraabdominal tumor model, we randomly divided the mice into two groups (n = 6 per group). PO-BDNF-AS-HGC-27 cells or PONC-BDNF-AS-HGC-27 cells (8 x 106) were suspended in 150 uL DMEM and intraperitoneally injected into the mice in each group (weight, approximately 18.0-19.0 g). Five weeks after injection, the mice were euthanized and necropsied to assess abdominal tumor burden and tumor location. Finally, we detected the mRNA and protein expression levels of relevant genes in the tumor tissues by RT-PCR and western blotting assays. REF000684 ICD-11: 2B72 Gastric cancer CELL00071; CELL00174; CELL00261; CELL00290; CELL00114; CELL00322 AGS; HGC-27; BGC-823; MGC-803; MKN-45; GES-1 Ferroptosis (hsa04216) Cell ferroptosis
unique00295 Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM. Suppressor . Up regulation . . Suppressor . REF000413 ICD-11: 2B72 Gastric cancer CELL00254; CELL00257 MKN74; NUGC4 Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01821 Amentoflavone suppressed the proliferation and induced ferroptotic cell death in gastric cancer cells via miR-496/ATF2 axis, indicating a novel therapeutic approach for GC patients. Inducer Down regulation . . Suppressor . The BALB/c nude mice (n = 15, 4-6 weeks old) were purchased from Charles River Labs and kept under controlled conditions. Then 1 x 106 AGS cells were inoculated subcutaneously into nude mice. When the tumor reached to 100 mm3, mice were randomly divided into three groups, the control group was intraperitoneally injected with saline, the AF group was intraperitoneally injected with AF at dosages of 80 mg/kg/day, and AF + anti-miR-496 group received intraperitoneal injection, followed by the administration of miR-496 antagonist via intra-tumor injection once a week for 4 weeks. REF001050 ICD-11: 2B72 Gastric cancer CELL10067; CELL00071; CELL00174 GSE-1; AGS; HGC-27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01739 The current work studied the role of Dexmedetomidine (DEX) in gastric cancer cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC. Inducer Down regulation . . Suppressor . Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections. REF000957 ICD-11: 2B72 Gastric cancer CELL00006; CELL00071; CELL00322 SNU1; AGS; GES-1 Ferroptosis (hsa04216) Cell ferroptosis
unique00762 We identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in gastric cancer cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cellsin vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1in vitro, which suggested that suggest that PB may increase the level of Fe2+by transporting Fe3+into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. Inducer Up regulation . . Driver . The nude mice were raised in our laboratory for a week before the experiment. Then, 5 x 106 MKN-1 cells were subcutaneously injected to establish the subcutaneous xenograft tumour model in nude mice. When the maximum diameter of the xenograft tumours grew steadily to 1 cm, they were dissected completely and cut into 1 mm3 tissue fragments. Then, the tissue fragment was inserted into the surface of the serosa on the greater curvature of the stomach. Different doses of PB (2.5 mg/kg or 5.0 mg/kg) were given by intraperitoneal injection once a day for 3 weeks. The control group was given the same volume of vehicle. The positive control group was given 5-Fu at the dose of 10 mg/kg. The body weight and tumour size of nude mice were recorded. Mice were administered fluorescein substrate (150 mg/kg) intraperitoneally for in vivo imaging twice a week on a Xenogen IVIS 200 imaging system (Caliper Life Sciences, USA). The tumour inhibition rate was analysed using LT Living Image 4.3 Software. REF000984 ICD-11: 2B72 Gastric cancer CELL00208; CELL00192; CELL00114; CELL00174; CELL00257 NUGC-3; MKN-1; MKN-45; HGC-27; NUGC-4 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01822 Amentoflavone suppressed the proliferation and induced ferroptotic cell death in gastric cancer cells via miR-496/ATF2 axis, indicating a novel therapeutic approach for GC patients. Inducer Up regulation . . Driver . The BALB/c nude mice (n = 15, 4-6 weeks old) were purchased from Charles River Labs and kept under controlled conditions. Then 1 x 106 AGS cells were inoculated subcutaneously into nude mice. When the tumor reached to 100 mm3, mice were randomly divided into three groups, the control group was intraperitoneally injected with saline, the AF group was intraperitoneally injected with AF at dosages of 80 mg/kg/day, and AF + anti-miR-496 group received intraperitoneal injection, followed by the administration of miR-496 antagonist via intra-tumor injection once a week for 4 weeks. REF001050 ICD-11: 2B72 Gastric cancer CELL10067; CELL00071; CELL00174 GSE-1; AGS; HGC-27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01740 The current work studied the role of Dexmedetomidine (DEX) in Gastric cancer (GC) cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC. Inducer Down regulation . . Suppressor . Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections. REF000957 ICD-11: 2B72 Gastric cancer CELL00006; CELL00071; CELL00322 SNU1; AGS; GES-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01738 The current work studied the role of Dexmedetomidine (DEX) in Gastric cancer (GC) cells and discovered that DEX suppressed GC growth by causing ferroptosis. Furthermore, the circ0008035/miR-302a/E2F7 axis was involved in DEX-induced ferroptotic cell death in GC. Inducer Up regulation . . Driver . Female BALB/c nude mice (4-6 weeks old) were obtained from Beijing Institute of Life Sciences (Beijing, China) and the mice were maintained under the standard conditions. AGS cells (2 x 106 cells/mL) were suspended in 100 ul of PBS and were subcutaneously injected in the right flank of mice. After 1 week, mice were divided into four groups (n = 5): Ctrl, 0.5 ug/kg, 1.0 ug/kg, and 2.0 ug/kg groups. The mice were intraperitoneally injected with DEX once a day for 15 days. Mice in the control group were injected with the same amount of normal saline. Tumor size was measured every 2 days and calculated with the formula: 0.5 x length x width2. After the last DEX injection was completed, mice were euthanized with sodium pentobarbital (100 mg/kg) and then sacrificed by decapitation. The tumor tissues were isolated and weighted. Immunohistochemistry for Ki67 and TUNEL assay were performed on paraffin-embedded xenograft tumor tissue sections. REF000957 ICD-11: 2B72 Gastric cancer CELL00006; CELL00071; CELL00322 SNU1; AGS; GES-1 Ferroptosis (hsa04216) Cell ferroptosis
unique00865 BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis in Colon cancer. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib). Inducer . Up regulation . . Driver To generate murine subcutaneous tumors, 5 x 106 HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 106 KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female). REF000045 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00120; CELL00095; CELL00143; CELL00049; CELL00057 HCT116; PANC1; HT1080; Calu-1; HeLa; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
dupunique01592 RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4 in colon carcinoma cells, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis. . . . Down regulation Driver Suppressor . REF000796 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00049; CELL00057; CELL00307 HCT116; Hela; HEK293T; HIEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01590 RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis in Colon carcinoma. . . . Up regulation Suppressor Suppressor . REF000796 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00049; CELL00057; CELL00307 HCT116; Hela; HEK293T; HIEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01591 RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis in Colon carcinoma. . . . Down regulation Driver Suppressor . REF000796 ICD-11: 2B90 Colon carcinoma CELL00087; CELL00049; CELL00057; CELL00307 HCT116; Hela; HEK293T; HIEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00330 Honokiol reduced the viability of Colon cancer (CC) cell lines by increasing ROS and Fe2+levels. HNK decreased the activity of Glutathione Peroxidase 4 (GPX4) but did not affect system Xc-. Thus, HNK can induce ferroptosis in CC cells by reducing the activity of GPX4. Inducer . Down regulation . . Suppressor Ten BALB/c nude mice (male, 4 weeks old, 18.0 ± 2.0 g) were randomly divided into two groups for the in vivo xenograft assay. Mice were injected with 5 x 106 RKO cells with stable overexpression GPX4 (described Lv-GPX4 group), control vector (described Lv-NC group). Cells were subcutaneously injected into the right anterior axilla of mice in both groups. Mice then received HNK (0.5 mg/kg/w) by intraperitoneal injection for 4 weeks. The subcutaneous tumor volumes in the nude mice in the two groups were recorded every two days. REF000452 ICD-11: 2B90 Colon cancer CELL00223; CELL00562; CELL00190; CELL00087; CELL00250; CELL00122; CELL00018 SW48; HT29; LS174T; HCT116; HCT8; RKO; SW480 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00570 Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer. Inducer . Down regulation . . Suppressor Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 106 RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days. REF000799 ICD-11: 2B90 Colon cancer CELL00122; CELL00087; CELL00118 RKO; HCT116; NCM460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00571 Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer. Inducer . Up regulation . . Marker/Suppressor/Driver Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 106 RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days. REF000799 ICD-11: 2B90 Colon cancer CELL00122; CELL00087; CELL00118 RKO; HCT116; NCM460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01507 LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. . . . Down regulation Driver Suppressor Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks. REF000725 ICD-11: 2B90 Colon cancer CELL00018; CELL00562; CELL00057 SW480; HT29; HEK293T Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell stemness
unique01506 LINC01606 functions as an oncogene to facilitate tumor cell stemness, proliferation and inhibit ferroptosis and is a promising therapeutic target for colon cancer. Mechanistically, LINC01606 enhanced the expression of stearoyl-CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR-423-5p expression, subsequently activating the canonical Wnt/-catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. . . . Up regulation Suppressor Suppressor Four-week-old female nude mice were purchased from Cavens (Changzhou, China). Nude mice were randomly divided into four groups. SW480 and HT29 cells infected with sh-LINC01606, Lv-LINC01606 and control vectors were subcutaneously implanted in mice (n = 6 per group), respectively. Tumour volumes (V = length x width2/2) were measured every 3 days, and tumour weights were determined after 4 weeks. REF000725 ICD-11: 2B90 Colon cancer CELL00018; CELL00562; CELL00057 SW480; HT29; HEK293T Wnt signaling pathway (hsa04310); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell stemness
unique00731 Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model. Inducer Down regulation . . Suppressor . HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately). REF000951 ICD-11: 2B90 Colon cancer CELL00087; CELL00562; CELL00122; CELL00109; CELL00133 HCT116; HT29; RKO; LOVO; SW620 Ferroptosis (hsa04216) Cell ferroptosis
dupunique00731 Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model. Inducer Up regulation . . Driver . HCT-116 cells (5 x 106) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately). REF000951 ICD-11: 2B90 Colon cancer CELL00087; CELL00562; CELL00122; CELL00109; CELL00133 HCT116; HT29; RKO; LOVO; SW620 Ferroptosis (hsa04216) Cell ferroptosis
unique00017 The study synthesized a series of Albiziabioside A derivatives and evaluated the antitumor activity both in vitro and in vivo. Compound D13 could induce apoptosis and ferroptosis through the mitochondrial pathway as a p53 activator. In addition, compound D13 significantly suppressed tumorigenesis without inducing toxicity in normal organs in vivo. The antitumor efficacy of D13 was further verified in colon cancer xenograft mouse models. Inducer Up regulation . . Driver . A total of 1 x 107 HCT116 cells were subcutaneously inoculated into the right flank of BALB/c mice. When tumor reached 70-100 mm3 (10 days after implant), mice were divided into five groups of eight animals at random. The groups with D13 were administered intravenously 20 mg/kg and 10 mg/kg. The positive control group was treated with AlbA(20 mg/kg and 10 mg/kg) through intravenous injection. The negative control group received 0.9% normal saline through intravenous injection. REF000047 ICD-11: 2B90 Colon cancer CELL00002; CELL00087; CELL10021; CELL00304; CELL00053; CELL00250; CELL00048; CELL00045; CELL00419; CELL00076; CELL00291 MCF-7; HCT116; HBMEC; L-O2; Hacat; HCT-8; HepG2; A549; CCD841; BEAS-2B; Bel-7402 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01802 The expression level of ACSL4 decreased and that of GPX4 increased when WIPI2 was knocked down, suggesting that WIPI2 can potentially positively regulate colorectal cancer ferroptosis. . . . Up regulation Driver Driver . REF001032 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00562 HCT116; HT29 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00202 Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy. Inducer . Up regulation . . Driver 5 x 106 HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm3, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. REF000267 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018; CELL00133 HCT116; SW480; SW620 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01269 MiR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. In addition, SAPK/JNK is the upstream molecule of p53. MiR-539 is a new therapeutic target for colorectal cancer (CRC) patients. . . . Down regulation Driver Suppressor Six 4-week-old male BALB/c nude mice were ordered from the Shanghai Laboratory Animal Center (Shanghai SLAC Laboratory Animal Co., Ltd., China). A total of 5 x 106 TIPE+/+ SW480 cells were suspended in 100 uL of PBS and subcutaneously injected into the right axilla flank of each nude mouse, and the same amount of vector SW480 cells was into the left. At 2 weeks after inoculation, the xenograft tumor size was measured using Vernier calipers every 2 days. REF000524 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018; CELL00057 HCT116; SW480; 293T Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
dupunique01269 MiR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. In addition, SAPK/JNK is the upstream molecule of p53. MiR-539 is a new therapeutic target for colorectal cancer (CRC) patients. . . . Down regulation Driver Suppressor Six 4-week-old male BALB/c nude mice were ordered from the Shanghai Laboratory Animal Center (Shanghai SLAC Laboratory Animal Co., Ltd., China). A total of 5 x 106 TIPE+/+ SW480 cells were suspended in 100 uL of PBS and subcutaneously injected into the right axilla flank of each nude mouse, and the same amount of vector SW480 cells was into the left. At 2 weeks after inoculation, the xenograft tumor size was measured using Vernier calipers every 2 days. REF000524 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018; CELL00057 HCT116; SW480; 293T Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00772 In conclusion, our study revealed that combined treatment with curcumin and andrographis exhibited anti-tumorigenic effects in colorectal cancer cells through activation of ferroptosis and by dual suppression of GPX-4 and FSP-1, which have significant potential implications for the adjunctive treatment of CRC patients. This combination treatment resulted in cancer cell death via both forms of cell death: apoptosis and ferroptosis. Inducer . Down regulation . . Suppressor Briefly, surgically resected tumors were maintained in DMEM-F12 (Gibco) supplemented with 1% HEPES (Sigma-Aldrich), 1% L-glutamine (Gibco), 10% FBS (Gibco), 2% penicillin/streptomycin (Sigma-Aldrich), and 10 uM Y-27632 (R&D Systems). Tumors were digested with collagenase solution (5 mL of the above medium with 75 uL collagenase, 124 ug/mL dispase type II, and 0.2% Primocen) for 30 min and then filtered through a 70 um filter (Corning). An organoid pellet was obtained by centrifugation (200x g for 10 min). Organoids were suspended in Matrigel (Corning, Tehama County, CA) with IntestiCult Organoid Growth Medium (#06010, STEMCELL Technologies) and seeded in 12-well plates. Approximately 750 uL of IntestiCult Organoid Growth Medium was added to each well. Organoids were divided into five groups of control, curcumin (3.0 ug/mL), andrographis (30.0 ug/mL), their combination (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL), and their combination plus ferrostatin-1 (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL; ferrostatin-1; 20 uM). Following forty-eight hours of treatment, the numbers of organoids (<100 um) and their mean sizes were examined using Image J software. REF000994 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018 HCT116; SW480 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00020 RSL3 triggered ferroptotic cell death by promoting the accumulation of cellular ROS and increasing the cellular LIP level. Mechanismly, we found transferrin expression were elevated in colorectal cancer cells treated with RSL3 accompanied by a decrease in the expression of GPX4, indicating an iron-dependent cell death. Inducer . Down regulation . . Suppressor . REF000055 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00562; CELL00109 HCT116; LoVo,HT29 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00773 In conclusion, our study revealed that combined treatment with curcumin and andrographis exhibited anti-tumorigenic effects in colorectal cancer cells through activation of ferroptosis and by dual suppression of GPX-4 and FSP-1, which have significant potential implications for the adjunctive treatment of CRC patients. This combination treatment resulted in cancer cell death via both forms of cell death: apoptosis and ferroptosis. Inducer . Down regulation . . Suppressor Briefly, surgically resected tumors were maintained in DMEM-F12 (Gibco) supplemented with 1% HEPES (Sigma-Aldrich), 1% L-glutamine (Gibco), 10% FBS (Gibco), 2% penicillin/streptomycin (Sigma-Aldrich), and 10 uM Y-27632 (R&D Systems). Tumors were digested with collagenase solution (5 mL of the above medium with 75 uL collagenase, 124 ug/mL dispase type II, and 0.2% Primocen) for 30 min and then filtered through a 70 um filter (Corning). An organoid pellet was obtained by centrifugation (200x g for 10 min). Organoids were suspended in Matrigel (Corning, Tehama County, CA) with IntestiCult Organoid Growth Medium (#06010, STEMCELL Technologies) and seeded in 12-well plates. Approximately 750 uL of IntestiCult Organoid Growth Medium was added to each well. Organoids were divided into five groups of control, curcumin (3.0 ug/mL), andrographis (30.0 ug/mL), their combination (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL), and their combination plus ferrostatin-1 (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL; ferrostatin-1; 20 uM). Following forty-eight hours of treatment, the numbers of organoids (<100 um) and their mean sizes were examined using Image J software. REF000994 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018 HCT116; SW480 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01698 TIMP1 depletion in colorectal cancer cells enhances sorafenib-triggered ferroptosis by reducing PI3K/Akt axis signal transduction. TIMP1 knockdown repressed the activation of the PI3K/Akt pathway and reduced levels of glutathione peroxidase 4 (GPX4), enhancing sorafenib-induced ferroptosis. . . . Up regulation Suppressor Suppressor . REF000921 ICD-11: 2B91 Colorectal cancer CELL00250 HCT8 Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique01548 HSPA5 restrained ferroptosis to promote colorectal cancer development by maintaining GPX4 stability. HSPA5 was demonstrated to play a diagnostic role and correlated to the immune microenvironment in CRC patients. . . . Up regulation Suppressor Suppressor Male BALB/c nude mice (4-6 weeks) were purchased from the Air Force Medical University Laboratory Animal Center. The mice were kept in the SPF environment and had free access to food and water. 3 x 106 SW480 cells were injected subcutaneously into nude mice (n = 4 or 5). Erastin was dissolved in 5% DMSO/corn oil and intraperitoneally injected into nude mice at a dose of 15 mg/kg three times. Three weeks later, mice were anesthetized by intraperitoneal injection of 10% chloral hydrate (35 mg/kg). When mice were successfully anesthetized five minutes later, mice were sacrificed and the tumors were resected and weighed. The tumors were divided into two parts. One sample was lysed and used for protein analysis. The other part was used to test for Ki67 expression. REF000762 ICD-11: 2B91 Colorectal cancer CELL00083; CELL00018 DLD1; SW480 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01813 Ferroptosis-related genes (FRGs) have potential prognostic value in colorectal cancer patients and that NOS2 suppresses tumor progression, providing a novel therapeutic target for CRC treatment based on ferroptosis. And NOS2 overexpression in CACO2 cells decreased the expression of GPX4. . . . Down regulation Driver Suppressor All nude mice were purchased from Guangdong Medical Laboratory Animal Center. NOS2-overexpressing and control cell lines were transplanted subcutaneously into the bilateral flanks, and appropriate care was given to these animals. REF001045 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018; CELL00133; CELL00046 HCT116; SW480; SW620; CACO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01005 Overexpression of ACADSB inhibits colorectal cancer cell migration, invasion, and proliferation, while ACADSB knockdown has the opposite effect. More importantly, ACADSB negatively regulates expression of glutathione reductase and glutathione peroxidase 4 (GPX4), the two main enzymes responsible for clearing glutathione (GSH) in CRC cells. . . . Down regulation Driver Suppressor . REF000208 ICD-11: 2B91 Colorectal cancer CELL00133; CELL00109 SW620; LoVo Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01091 SRSF9's regulation of GPX4 as an essential mechanism driving colorectal cancer (CRC) tumorigenesis and resistance of erastin-induced ferroptosis. This molecular mechanism may provide a novel method for improving the sensitivity of CRC to erastin. . . . Up regulation Suppressor Suppressor LOVO cells were stably transfected with SRSF9-shRNA1 or NC-shRNA. Caco-2 cells were stably transfected with SRSF9-OE or empty vector. Then the transfected CRC cells (2*105 cells/100 uL) were injected into the right armpit of mouse 6-8-week-old male athymic nude mice. When the tumors reached 50 mm3 at day 7, erastin (40 mg/kg) was administrated to mice by intraperitoneal injection twice every other day. REF000330 ICD-11: 2B91 Colorectal cancer CELL00046; CELL00087; CELL00133; CELL00109; CELL00083; CELL00018 Caco-2; HCT-116; SW-620; LOVO; DLD-1; SW-480 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01803 The expression level of ACSL4 decreased and that of GPX4 increased when WIPI2 was knocked down, suggesting that WIPI2 can potentially positively regulate colorectal cancer ferroptosis. . . . Down regulation Driver Suppressor . REF001032 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00562 HCT116; HT29 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01315 Overexpression of miR-15a-3p repressed GPX4 through binding to the 3'-untranslated region of GPX4, resulting in increased reactive oxygen species level, intracellular Fe2+ level, and malondialdehyde accumulation in vitro and in vivo. MiR-15a-3p suppressed colorectal cancer cell growth and enhanced cell ferroptosis by inactivating GPX4. . . . Down regulation Driver Suppressor We obtained the 6-week-old nude mice (BALB/c) from Beijing HFK Bioscience Co., Ltd. and randomly divided into eight groups (n = 5/group): (a) NC + dimethyl sulfoxide (DMSO) group; (b) NC + erastin group; (c) mimic + DMSO group; (d) mimic + erastin group; (e) iNC + DMSO group; (f) iNC + erastin group; (g) inhibitor + DMSO group; (h) inhibitor + erastin group. Control and transfected cells (7 x 106) were subcutaneously injected into the nude mice. After the tumor sizes reached roughly >50 mm3, mice in Groups B, D, F, and H were treated with 15 mg/kg erastin twice every day for about 20 days. Meanwhile, mice in Groups A, C, E, and G were treated with an equal volume DMSO. Besides, tumor formation and mass were monitored and the size of tumor was counted using the formula V = 0.5 x L x W2 (L, length and W, width). At last, after killing the nude mice and then we isolated the mice tumor tissues. REF000569 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00046; CELL00562; CELL00182; CELL00118 HCT-116; CaCo2; HT29; KM12; NCM460 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01602 LINC00239 plays a novel and indispensable role in ferroptosis by nucleotides 1-315 of LINC00239 to interact with the Kelch domain (Nrf2-binding site) of Keap1, inhibiting Nrf2 ubiquitination and increasing Nrf2 protein stability. And LINC00239 expression has a positive correlation with Nrf2 and GPX4 expression in colorectal cancer tissues. LINC00239 inhibition in combination with ferroptosis induction might be a promising therapeutic strategy for CRC patients. . . . Up regulation Suppressor Suppressor To clarify the role of LINC00239 in vivo, we used 4-week-old male BALB/c nude mice provided by the Experimental Animal Center of the Air Force Military Medical University. HCT116 or SW620 cells (1 x 107 cells) were injected subcutaneously into the right flanks of these mice to establish a CRC xenograft model. One week after the injection of cells, the volume of xenografts was continuously monitored (once a week). Four weeks later, the xenografts were removed, and the weights were measured. REF000810 ICD-11: 2B91 Colorectal cancer CELL00122; CELL00087; CELL00046; CELL00018; CELL00133; CELL00267 RKO; HCT116; CaCo2; SW480; SW620; FHC Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique00711 Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition. Suppressor . Up regulation . . Suppressor CT26 (1 x 105 cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 105 cells/100 uL, HT29: 1 x 106 cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging. REF000928 ICD-11: 2B91 Colorectal cancer CELL00562; CELL00561 HT29; CT26 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00203 Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy. Inducer . Up regulation . . Driver/Suppressor 5 x 106 HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm3, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. REF000267 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018; CELL00133 HCT116; SW480; SW620 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00348 Tagitinin C induces ferroptosis in colorectal cancer cells and has synergistic effect together with erastin. Mechanistically, tagitinin C induces ferroptosis through ER stress-mediated activation of PERK-Nrf2-HO-1 signaling pathway. Inducer . Up regulation . . Driver . REF000473 ICD-11: 2B91 Colorectal cancer CELL00087 HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00166 Combined treatment with andrographis was significantly more effective than 5FU and andrographis alone and that these effects were in part orchestrated through dysregulated expression of key genes (including HMOX1, GCLC, GCLM and TCF7L2) within the ferroptosis and Wnt-signaling pathways. Andrographis might offer a safe and inexpensive adjunctive therapeutic option in the management of colorectal cancer patients. Inducer . Up regulation . . Driver/Suppressor Seven-week-old male athymic nude mice (Envigo, Houston, TX) were housed under controlled conditions of light and fed ad libitum. Approximately 5 x 106 parental and 5FUR HCT116 cells were suspended in the matrigel matrix (BD Biosciences, Franklin Lakes, NJ) and subcutaneously injected into mice using a 27-gauge needle (n = 10 per group). Mice were randomly assigned to different treatment groups and 5FU (30 mg/kg body weight) or andrographis (125 mg/kg body weight) or their combination were given intraperitoneally on alternative days for up to 15 days. REF000221 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018 HCT116; SW480 Wnt signaling pathway (hsa04310); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01524 IREB2 was negatively regulated by miR-19a in Colorectal cancer (CRC) cells. In addition, ferroptosis was suppressed by miR-19a through inhibiting IREB2. . . . Down regulation Suppressor Driver . REF000744 ICD-11: 2B91 Colorectal cancer CELL00562 HT29 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00712 Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition. Suppressor . Up regulation . . Suppressor CT26 (1 x 105 cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 105 cells/100 uL, HT29: 1 x 106 cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging. REF000928 ICD-11: 2B91 Colorectal cancer CELL00562; CELL00561 HT29; CT26 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00710 Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition. Suppressor . Up regulation . . Marker/Suppressor CT26 (1 x 105 cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 105 cells/100 uL, HT29: 1 x 106 cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging. REF000928 ICD-11: 2B91 Colorectal cancer CELL00562; CELL00561 HT29; CT26 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00528 Oxaliplatin promoted ferroptosis and oxidative stress in colorectal cancer cells by inhibiting the Nrf2 signaling pathway. Treatment with oxaliplatin enhanced the effects of erastin on CRC cells by promoting ferroptosis and oxidative stress and inhibiting cell viability. Inducer . Down regulation . . Marker/Suppressor . REF000729 ICD-11: 2B91 Colorectal cancer CELL00562 HT29 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00347 Tagitinin C induces ferroptosis in colorectal cancer cells and has synergistic effect together with erastin. Mechanistically, tagitinin C induces ferroptosis through ER stress-mediated activation of PERK-Nrf2-HO-1 signaling pathway. Inducer . Up regulation . . Marker/Suppressor . REF000473 ICD-11: 2B91 Colorectal cancer CELL00087 HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01141 KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among colorectal cancer patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation. Moreover, silencing NUAK1 up-regulated the expression of PP1, down-regulated the phosphorylation of downstream GSK3Ser9, suppressed the nuclear import of Nrf2, inhibited the expression of a ferroptosis key negative regulatory protein (GPX4), and blocked cellular resistance. . . . Up regulation Suppressor Marker/Suppressor HCT116-Or or H716 cells (7*106) were suspended into 200 ul matrigel (BD Bioscience), and injected into the subcutaneous tissues of mouse right lower limbs. Animals were grouped randomly (eight mouse per group) and medication was initiated when the average xenograft size was over 100 mm3: Oxaliplatin was given alone weekly through intraperitoneal injection (5 mg/kg), or in combination with liproxstatin-1 through intraperitoneal injection for twice a week (125 mg/kg) and RSL3 through intra-tumor injection (100 mg/kg, in order to achieve better local concentration and reduce the probable systemic toxicity of RSL3) weekly. REF000375 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00381 HCT116; H716 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01603 LINC00239 plays a novel and indispensable role in ferroptosis by nucleotides 1-315 of LINC00239 to interact with the Kelch domain (Nrf2-binding site) of Keap1, inhibiting Nrf2 ubiquitination and increasing Nrf2 protein stability. And LINC00239 expression has a positive correlation with Nrf2 and GPX4 expression in colorectal cancer tissues. LINC00239 inhibition in combination with ferroptosis induction might be a promising therapeutic strategy for CRC patients. . . . Down regulation Driver Marker/Suppressor To clarify the role of LINC00239 in vivo, we used 4-week-old male BALB/c nude mice provided by the Experimental Animal Center of the Air Force Military Medical University. HCT116 or SW620 cells (1 x 107 cells) were injected subcutaneously into the right flanks of these mice to establish a CRC xenograft model. One week after the injection of cells, the volume of xenografts was continuously monitored (once a week). Four weeks later, the xenografts were removed, and the weights were measured. REF000810 ICD-11: 2B91 Colorectal cancer CELL00122; CELL00087; CELL00046; CELL00018; CELL00133; CELL00267 RKO; HCT116; CaCo2; SW480; SW620; FHC Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique01142 KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among colorectal cancer patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation. Moreover, silencing NUAK1 up-regulated the expression of PP1, down-regulated the phosphorylation of downstream GSK3Ser9, suppressed the nuclear import of Nrf2, inhibited the expression of a ferroptosis key negative regulatory protein (GPX4), and blocked cellular resistance. . . . Up regulation Suppressor Marker/Suppressor HCT116-Or or H716 cells (7*106) were suspended into 200 ul matrigel (BD Bioscience), and injected into the subcutaneous tissues of mouse right lower limbs. Animals were grouped randomly (eight mouse per group) and medication was initiated when the average xenograft size was over 100 mm3: Oxaliplatin was given alone weekly through intraperitoneal injection (5 mg/kg), or in combination with liproxstatin-1 through intraperitoneal injection for twice a week (125 mg/kg) and RSL3 through intra-tumor injection (100 mg/kg, in order to achieve better local concentration and reduce the probable systemic toxicity of RSL3) weekly. REF000375 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00381 HCT116; H716 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01601 LINC00239 plays a novel and indispensable role in ferroptosis by nucleotides 1-315 of LINC00239 to interact with the Kelch domain (Nrf2-binding site) of Keap1, inhibiting Nrf2 ubiquitination and increasing Nrf2 protein stability. And LINC00239 expression has a positive correlation with Nrf2 and GPX4 expression in CRC tissues. LINC00239 inhibition in combination with ferroptosis induction might be a promising therapeutic strategy for colorectal cancer patients. . . . Up regulation Suppressor Marker/Suppressor To clarify the role of LINC00239 in vivo, we used 4-week-old male BALB/c nude mice provided by the Experimental Animal Center of the Air Force Military Medical University. HCT116 or SW620 cells (1 x 107 cells) were injected subcutaneously into the right flanks of these mice to establish a CRC xenograft model. One week after the injection of cells, the volume of xenografts was continuously monitored (once a week). Four weeks later, the xenografts were removed, and the weights were measured. REF000810 ICD-11: 2B91 Colorectal cancer CELL00122; CELL00087; CELL00046; CELL00018; CELL00133; CELL00267 RKO; HCT116; CaCo2; SW480; SW620; FHC Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique00713 Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition. Suppressor . Up regulation . . Suppressor CT26 (1 x 105 cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 105 cells/100 uL, HT29: 1 x 106 cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging. REF000928 ICD-11: 2B91 Colorectal cancer CELL00562; CELL00561 HT29; CT26 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00109 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) significantly induced the ferroptosis of colorectal cancer cells. Mechanistically, IMCA downregulated the expression of SLC7A11 and decreased the contents of cysteine and glutathione, which resulted in reactive oxygen species accumulation and ferroptosis. Inducer . Down regulation . . Suppressor Five-week-old female BALB/c nude mice were purchased from Beijing Weitong Lihua Experimental Animal Technical Co., Ltd. (Beijing, China). The mice were randomly assigned to the treatment and control groups until the tumor size reached approximately 100 mm3. The mice in the treatment group were injected with 0.174 mg/mL IMCA (100 uL), and those in the control group were injected with an equal volume of normal saline. The nude mice were euthanized, and samples were obtained from their tumor, heart, hepar, kidney, and blood after 33 days of IMCA treatment. REF000163 ICD-11: 2B91 Colorectal cancer CELL00083; CELL00087 DLD-1; HCT-116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); mTOR signaling pathway (hsa04150) Cell ferroptosis; Cell proliferation
unique00201 Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy. Inducer . Down regulation . . Suppressor 5 x 106 HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm3, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. REF000267 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018; CELL00133 HCT116; SW480; SW620 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01370 MiR-545 inhibits ferroptosis in colorectal cancer cells by inhibiting TF. TF overexpression blocked miR-545-induced changes in ROS, MDA, and Fe2+ levels in HT-29 and HCT-116 cells, thereby inducing CRC cell death. . . . Down regulation Suppressor Marker/Suppressor/Driver 5-week-old immunodeficient nude mice (male, weight, 16-20 g, n = 40 mice for each group) were purchased from Cyagen bio. Co. (Beijing, China). Before experiments, the mice were adapted to the breeding environment for two weeks. All mice were maintained at a 12 h/12 h light/dark cycle with free access to water and food. A total of 5 x 106 HT-29 or HCT-116 cells were suspended in 100 uL PBS and injected subcutaneously into the right posterior flanks of nude mice. After three weeks, the mice were killed and the tumor xenografts were dissected, weighed and fixed in 10% buffered formaldehyde for further IHC analysis. REF000624 ICD-11: 2B91 Colorectal cancer CELL00118; CELL00096; CELL00087; CELL00109 NCM460; HT-29; HCT-116; LoVo Ferroptosis (hsa04216) Cell ferroptosis
unique00774 In conclusion, our study revealed that combined treatment with curcumin and andrographis exhibited anti-tumorigenic effects in colorectal cancer cells through activation of ferroptosis and by dual suppression of GPX-4 and FSP-1, which have significant potential implications for the adjunctive treatment of CRC patients. This combination treatment resulted in cancer cell death via both forms of cell death: apoptosis and ferroptosis. Inducer . Down regulation . . Suppressor Briefly, surgically resected tumors were maintained in DMEM-F12 (Gibco) supplemented with 1% HEPES (Sigma-Aldrich), 1% L-glutamine (Gibco), 10% FBS (Gibco), 2% penicillin/streptomycin (Sigma-Aldrich), and 10 uM Y-27632 (R&D Systems). Tumors were digested with collagenase solution (5 mL of the above medium with 75 uL collagenase, 124 ug/mL dispase type II, and 0.2% Primocen) for 30 min and then filtered through a 70 um filter (Corning). An organoid pellet was obtained by centrifugation (200x g for 10 min). Organoids were suspended in Matrigel (Corning, Tehama County, CA) with IntestiCult Organoid Growth Medium (#06010, STEMCELL Technologies) and seeded in 12-well plates. Approximately 750 uL of IntestiCult Organoid Growth Medium was added to each well. Organoids were divided into five groups of control, curcumin (3.0 ug/mL), andrographis (30.0 ug/mL), their combination (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL), and their combination plus ferrostatin-1 (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL; ferrostatin-1; 20 uM). Following forty-eight hours of treatment, the numbers of organoids (<100 um) and their mean sizes were examined using Image J software. REF000994 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018 HCT116; SW480 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00775 In conclusion, our study revealed that combined treatment with curcumin and andrographis exhibited anti-tumorigenic effects in colorectal cancer cells through activation of ferroptosis and by dual suppression of GPX-4 and FSP-1, which have significant potential implications for the adjunctive treatment of CRC patients. This combination treatment resulted in cancer cell death via both forms of cell death: apoptosis and ferroptosis. Inducer . Down regulation . . Suppressor Briefly, surgically resected tumors were maintained in DMEM-F12 (Gibco) supplemented with 1% HEPES (Sigma-Aldrich), 1% L-glutamine (Gibco), 10% FBS (Gibco), 2% penicillin/streptomycin (Sigma-Aldrich), and 10 uM Y-27632 (R&D Systems). Tumors were digested with collagenase solution (5 mL of the above medium with 75 uL collagenase, 124 ug/mL dispase type II, and 0.2% Primocen) for 30 min and then filtered through a 70 um filter (Corning). An organoid pellet was obtained by centrifugation (200x g for 10 min). Organoids were suspended in Matrigel (Corning, Tehama County, CA) with IntestiCult Organoid Growth Medium (#06010, STEMCELL Technologies) and seeded in 12-well plates. Approximately 750 uL of IntestiCult Organoid Growth Medium was added to each well. Organoids were divided into five groups of control, curcumin (3.0 ug/mL), andrographis (30.0 ug/mL), their combination (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL), and their combination plus ferrostatin-1 (curcumin; 3.0 ug/mL, andrographis; 30.0 ug/mL; ferrostatin-1; 20 uM). Following forty-eight hours of treatment, the numbers of organoids (<100 um) and their mean sizes were examined using Image J software. REF000994 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018 HCT116; SW480 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00422 Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling. The dual PI3K/HDAC inhibitor BEBT-908 elicits potent antitumor responses, effectively inducing immunogenic ferroptosis of colorectal cancer cells and potentiating cancer immunotherapy. Inducer Down regulation . . Suppressor . About 2 x 105 MC38 tumor cells were inoculated subcutaneously into C57BL/6 mice. A total of 100 mg/kg BEBT-908 was intravenously injected every other day for four times initiating from day 4 after tumor cell inoculation. Tumors were harvested on day 12 after inoculation, weighted, mechanically minced and incubated with 50 ug/mL DNase I (Sigma) and 2 mg/mL collagenase P (Sigma) for 20 minutes at 37. REF000564 ICD-11: 2B91 Colorectal cancer CELL00318 MC38 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis; Cell proliferation
dupunique00422 Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling. The dual PI3K/HDAC inhibitor BEBT-908 elicits potent antitumor responses, effectively inducing immunogenic ferroptosis of colorectal cancer cells and potentiating cancer immunotherapy. Inducer Up regulation . . Driver . About 2 x 105 MC38 tumor cells were inoculated subcutaneously into C57BL/6 mice. A total of 100 mg/kg BEBT-908 was intravenously injected every other day for four times initiating from day 4 after tumor cell inoculation. Tumors were harvested on day 12 after inoculation, weighted, mechanically minced and incubated with 50 ug/mL DNase I (Sigma) and 2 mg/mL collagenase P (Sigma) for 20 minutes at 37. REF000564 ICD-11: 2B91 Colorectal cancer CELL00318 MC38 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis; Cell proliferation
unique00457 Auriculasin promoted the expression of Keap1 and AIFM1, but significantly reduced the phosphorylation level of AIFM1. AC can promote colorectal cancer cell apoptosis, ferroptosis and oxeiptosis by inducing ROS generation, thereby inhibiting cell viability, invasion and colony formation, indicating that AC has a significant tumor suppressor effect. Inducer Up regulation . . Driver . . REF000601 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018 HCT116; SW480 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell invasion
unique00458 Auriculasin promoted the expression of Keap1 and AIFM1, but significantly reduced the phosphorylation level of AIFM1. AC can promote colorectal cancer cell apoptosis, ferroptosis and oxeiptosis by inducing ROS generation, thereby inhibiting cell viability, invasion and colony formation, indicating that AC has a significant tumor suppressor effect. Inducer Up regulation . . Driver . . REF000601 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018 HCT116; SW480 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell invasion
unique01070 Pirin (PIR), an iron-binding nuclear protein, plays a previously unrecognized role in mediating ferroptosis resistance in human pancreatic cancer cells. The depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4. . . . Down regulation Suppressor Driver To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and treated with IKE (imidazole ketone erastin; 40 mg/kg; i.p., once every other day) for 3 weeks, and then samples were collected and assayed. REF000293 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00013; CELL00045; CELL00048 PANC1; MIAPaCa2; A549; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01071 Pirin (PIR), an iron-binding nuclear protein, plays a previously unrecognized role in mediating ferroptosis resistance in human pancreatic cancer cells. The depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4. . . . Up regulation Driver Driver To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-oldathymic nude mice(n = 5 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and treated with IKE (imidazole ketone erastin; 40 mg/kg; i.p., once every other day) for 3 weeks, and then samples were collected and assayed. REF000293 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00013; CELL00045; CELL00048 PANC1; MIAPaCa2; A549; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00978 ARF6, functioned as a downstream of Kras/ERK signaling pathway, could promote proliferation and Warburg effect in pancreatic cancer cells. ARF6 decreased ACSL4 protein level and this effect endowed pancreatic cancer cells to a status that sensitized to oxidative stress. . . . Down regulation Suppressor Driver . REF000169 ICD-11: 2C10 Pancreatic cancer CELL00149; CELL00073; CELL00120; CELL00008; CELL00222; CELL00082; CELL00013 H6C7; AsPC-1; PANC-1; BxPC3; SW1990; Capan-1; MIA PaCa-2 Ferroptosis (hsa04216); Ras signaling pathway (hsa04014) Cell ferroptosis; Cell proliferation
unique01388 PTPMT1 is upregulated in PDAC and PTPMT1 inhibits ferroptosis by suppressing the expression of ACSL4 and upregulating SLC7A11 in Panc-1 cells, suggesting PTPMT1 might be a potential prognosis biomarker and therapeutic target in pancreatic cancer. . . . Down regulation Suppressor Driver . REF000638 ICD-11: 2C10 Pancreatic cancer CELL00120 Panc-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00533 Dihydroartemisinin has anti-tumor effect in pancreatic cancer cells in vitro and in vivo. DHA treatment induced ferroptosis by increasing P53 and AOLX12 expression. Inducer . Up regulation . . Driver Six to eight-week-old female C57BL/6 mice were purchased from the Experimental Animal Center of Military Medical Sciences (Beijing, China). C57BL/6 mice were anesthetized and the tail of the pancreas was exposed. Panc 02 cells were resuspended in PBS at a concentration of 1 x 106 cells/0.1 ml and 50 ul cells were injected into the tail of the pancreas. Tumor-bearing mice were randomly divided into two groups (3 days after implantation). The control group was intraperitoneally injected 200 ul PBS daily for 10 days, and the DHA group was intraperitoneally injected with 100 mg/kg DHA daily for 10 days. The pancreatic tumors and spleens of the mice were collected for subsequent analysis. REF000739 ICD-11: 2C10 Pancreatic cancer CELL00025; CELL00120 Panc 02; Panc1 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01083 MGST1 inhibits ferroptotic cancer cell death partly by binding to ALOX5, resulting in reduced lipid peroxidation. The expression of MGST1 is positively correlated with NFE2L2 expression in pancreatic tumors, which is implicated in the poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). . . . Down regulation Suppressor Driver To generate murine subcutaneous tumors, 5 x 106 CFPAC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude female mice. Once the tumors reached around 70-80 mm3 at day 7, mice were randomly allocated into groups and then treated with imidazole ketone erastin (IKE; 40 mg/kg, i.p., once every other day) in the absence or presence of liproxstatin-1 (10 mg/kg, i.p., once every other day) for 2 weeks. REF000313 ICD-11: 2C10.0 Pancreatic ductal adenocarcinoma CELL00160; CELL00212; CELL00120; CELL00013; CELL00045; CELL00048 CFPAC1; PANC2.03; PANC1; MIAPaCa2; A549; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis
unique01608 Cold induction promotes the process of ferroptosis by inducing the expression of CIRBP and then regulating key factors such as p53 and GPX4. In addition, cold induction significantly inhibited the proliferation of pancreatic cancer cells and induced cell apoptosis, but after the addition of ferroptosis inhibitor, cell proliferation and apoptosis did not change significantly. . . . Down regulation Driver Suppressor . REF000818 ICD-11: 2C10 Pancreatic cancer CELL00008; CELL00120 BxPC-3; PANC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
dupunique01608 Cold induction promotes the process of ferroptosis by inducing the expression of CIRBP and then regulating key factors such as p53 and GPX4[. In addition, cold induction significantly inhibited the proliferation of pancreatic cancer cells and induced cell apoptosis, but after the addition of ferroptosis inhibitor, cell proliferation and apoptosis did not change significantly. . . . Down regulation Driver Suppressor . REF000818 ICD-11: 2C10 Pancreatic cancer CELL00008; CELL00120 BxPC-3; PANC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00757 Wogonin could significantly reduces pancreatic cancer cell proliferation and induce ferroptosisviathe Nrf2/GPX4 axis. Therefore, wogonin could be potentially used for treating patients with pancreatic cancer. Inducer . Down regulation . . Suppressor Female BALB/c nude mice (5 weeks old) were procured from Hangzhou Ziyuan Laboratory Animal Technology Co., Ltd (Zhejiang, China) and given 5 days to acclimate to their surroundings. PANC-1 cells (1 x 107) in 100 uL PBS at the logarithmic growth phase were administered to mice subcutaneously in the left flank. The mice were treated with indicated treatments after nearly 10 days when the tumour size was approximately 1,000 mm3. In the control group, mice (n = 5) received intraperitoneal injections of the vehicle. In the treatment group, the mice (n = 5) were administered 50 uL of 60 mg/kg body weight of wogonin once a day for 12 days. A slide calliper size was used to measure the tumour size. The equation for calculating tumour volume is as follows: tumour volume = AB2/2, wherein A is the length, and B is the width of the tumour. The mice were sacrificed the next day after the treatment procedure was complete by cervical dislocation. The tumour tissues were harvested and snap-frozen using liquid nitrogen for subsequent analyses. REF000981 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00073; CELL00149 PANC-1; AsPC-1; HPDE6-C7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00160 QD394 causes an iron- and ROS-dependent, GPX4 mediated cell death, suggesting ferroptosis as a major mechanism. Importantly, QD394 decreases the expression of LRPPRC and PNPT1. Pharmacokinetics-guided lead optimization resulted in the derivative QD394-Me, which showed improved plasma stability and reduced toxicity in mice compared to QD394. Overall, QD394 and QD394-Me represent novel ROS-inducing drug-like compounds warranting further development for the treatment of pancreatic cancer. Inducer . Down regulation . . Suppressor Female Balb/c mice were purchased from Envigo. At the time of implantation, all mice were aged 5-6 weeks. Mice were implanted subcutaneously in the right flank with 1 x 106 CT-26 cells in 100 uL DPBS. Seven days after implantation, mice were randomized into groups (n = 5) with mean tumor volumes ranging from 97 to 117 mm3. The negative control group was dosed daily in the intraperitoneal cavity (IP) with the same vehicle used for QD394. QD394 was dosed at 10 mg/kg IP, and QD394-Me was dosed 3 times weekly intravenously (IV) at 20 mg/kg. REF000214 ICD-11: 2C10 Pancreatic cancer CELL00013; CELL00120; CELL00008 MIA PaCa-2; PANC-1; BxPC-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00161 QD394 causes an iron- and ROS-dependent, GPX4 mediated cell death, suggesting ferroptosis as a major mechanism. Importantly, QD394 decreases the expression of LRPPRC and PNPT1. Pharmacokinetics-guided lead optimization resulted in the derivative QD394-Me, which showed improved plasma stability and reduced toxicity in mice compared to QD394. Overall, QD394 and QD394-Me represent novel ROS-inducing drug-like compounds warranting further development for the treatment of pancreatic cancer. Inducer . Down regulation . . Suppressor Female Balb/c mice were purchased from Envigo. At the time of implantation, all mice were aged 5-6 weeks. Mice were implanted subcutaneously in the right flank with 1 x 106 CT-26 cells in 100 uL DPBS. Seven days after implantation, mice were randomized into groups (n = 5) with mean tumor volumes ranging from 97 to 117 mm3. The negative control group was dosed daily in the intraperitoneal cavity (IP) with the same vehicle used for QD394. QD394 was dosed at 10 mg/kg IP, and QD394-Me was dosed 3 times weekly intravenously (IV) at 20 mg/kg. REF000214 ICD-11: 2C10 Pancreatic cancer CELL00013; CELL00120; CELL00008 MIA PaCa-2; PANC-1; BxPC-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00835 The HSPA5-GPX4 pathway mediated ferroptosis resistance, limiting the anticancer activity of gemcitabine. Genetic or pharmacologic inhibition of the HSPA5-GPX4 pathway enhanced gemcitabine sensitivity by disinhibiting ferroptosisin vitroand in both subcutaneous and orthotopic animal models of pancreatic ductal adenocarcinoma. . . . Up regulation Suppressor Marker/Suppressor To generate murine subcutaneous tumors, 2 x 106 PANC1 cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached ~50 mm3 at day seven, mice were randomly allocated into groups and treated with chemotherapy for two weeks (n = 5 mice/group). To generate orthotopic tumors, B6 mice were surgically implanted with 1 x 106 Panc02 into the tail of the pancreas. Two weeks after implantation, mice were randomly allocated into groups and treated with chemotherapy for three weeks (n = 6 mice/group). REF000018 ICD-11: 2C10.0 Pancreatic ductal adenocarcinoma CELL00120; CELL00160; CELL00013; CELL00212; CELL00025 PANC1; CFPAC1; MiaPaCa2; Panc2.03; Panc02 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01103 High expression of the KAI1 (CD82) gene promoted the occurrence of ferroptosis in pancreatic cancer cells through its extensive effect on FPN and GPX4. KAI1induced ferroptosis did not significantly inhibit the proliferation of PC cells. . . . Up regulation Driver Marker/Suppressor . REF000343 ICD-11: 2C10 Pancreatic cancer CELL00013 PaCa-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00948 Elevation of mitochondrial LONP1 in erastin-induced ferroptosis of pancreatic cancer cell lines. Inhibition of LONP1 activates the Nrf2/Keap1 signal pathway and up-regulates the expression of GPX4, a key peroxidase in regulating ferroptosis. . . . Down regulation Driver Suppressor . REF000117 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00008 PANC1; BxPC3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Pathways in cancer (hsa05200) Cell ferroptosis; Cell proliferation
unique00988 The interplay between the signals of mechanistic target of rapamycin kinase (MTOR) and glutathione peroxidase 4 (GPX4) modulates autophagy-dependent ferroptosis in human pancreatic cancer cells. Both the classical autophagy inducer rapamycin and the classical ferroptosis activator RSL3 can block MTOR activation and cause GPX4 protein degradation in human pancreatic cancer cells. . . . Up regulation Suppressor Suppressor To generate murine subcutaneous tumors, 5 x 106 PANC1 or MIAPaCa2 cells in 100 ul PBS were injected subcutaneously into the right of the dorsal midline in 6- to 8-week-old athymic nude or B6 mice (female). Once the tumors reached 50-70 mm3 at day 7, mice were randomly allocated into groups and treated with rapamycin (20 mg/kg; i.p., once every other day) in the absence or presence of liproxstatin-1 (10 mg/kg; i.p., once every other day) or hydroxychloroquine (50 mg/kg; i.p., once every other day) for 2 weeks. REF000181 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00013; CELL00222 PANC1; MIAPaCa2; SW1990 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00424 Itaconic acid-induced expression and activation of NFE2L2 serves as a defense mechanism to limit ferroptosis by producing antioxidant genes. Consequently, impaired NCOA4 expression prevented, whereas a disrupted NFE2L2 pathway enhanced, sensitivity to itaconic acid-induced ferroptosis in pancreatic cancer cells. Inducer . Up regulation . . Driver To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously into the right of the dorsal midline in 6- to 8-week-old femaleathymic nude mice(n = 6 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and then given intraperitoneal injections with itaconic acid (50 mg/kg, once every other day) at day 7 for 2 weeks. REF000571 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00038 PANC1; THP1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00831 Autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and pancreatic cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis. . . . Up regulation Driver Driver . REF000011 ICD-11: 2C10 Pancreatic cancer CELL10119; CELL00120; CELL00212; CELL00095; CELL00120 MEFs; PANC1; PANC2.03; HT-1080; PANC1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00830 Autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and pancreatic cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis. . . . Up regulation Driver Driver . REF000011 ICD-11: 2C10 Pancreatic cancer CELL10119; CELL00120; CELL00212; CELL00095; CELL00120 MEFs; PANC1; PANC2.03; HT-1080; PANC1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00425 Itaconic acid-induced expression and activation of NFE2L2 serves as a defense mechanism to limit ferroptosis by producing antioxidant genes. Consequently, impaired NCOA4 expression prevented, whereas a disrupted NFE2L2 pathway enhanced, sensitivity to itaconic acid-induced ferroptosis in pancreatic cancer cells. Suppressor . Up regulation . . Marker/Suppressor To generate murine subcutaneous tumors, 5 x 106 PANC1 cells in 100 ul PBS were injected subcutaneously into the right of the dorsal midline in 6- to 8-week-old femaleathymic nude mice(n = 6 mice/group). After the tumor reached 60-80 mm3 on day 7, the mice were randomly grouped and then given intraperitoneal injections with itaconic acid (50 mg/kg, once every other day) at day 7 for 2 weeks. REF000571 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00038 PANC1; THP1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00756 Wogonin could significantly reduces pancreatic cancer cell proliferation and induce ferroptosisviathe Nrf2/GPX4 axis. Therefore, wogonin could be potentially used for treating patients with pancreatic cancer. Inducer . Down regulation . . Marker/Suppressor Female BALB/c nude mice (5 weeks old) were procured from Hangzhou Ziyuan Laboratory Animal Technology Co., Ltd (Zhejiang, China) and given 5 days to acclimate to their surroundings. PANC-1 cells (1 x 107) in 100 uL PBS at the logarithmic growth phase were administered to mice subcutaneously in the left flank. The mice were treated with indicated treatments after nearly 10 days when the tumour size was approximately 1,000 mm3. In the control group, mice (n = 5) received intraperitoneal injections of the vehicle. In the treatment group, the mice (n = 5) were administered 50 uL of 60 mg/kg body weight of wogonin once a day for 12 days. A slide calliper size was used to measure the tumour size. The equation for calculating tumour volume is as follows: tumour volume = AB2/2, wherein A is the length, and B is the width of the tumour. The mice were sacrificed the next day after the treatment procedure was complete by cervical dislocation. The tumour tissues were harvested and snap-frozen using liquid nitrogen for subsequent analyses. REF000981 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00073; CELL00149 PANC-1; AsPC-1; HPDE6-C7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01082 MGST1 inhibits ferroptotic cancer cell death partly by binding to ALOX5, resulting in reduced lipid peroxidation. The expression of MGST1 is positively correlated with NFE2L2 expression in pancreatic tumors, which is implicated in the poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). . . . Up regulation Suppressor Marker/Suppressor To generate murine subcutaneous tumors, 5 x 106 CFPAC1 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude female mice. Once the tumors reached around 70-80 mm3 at day 7, mice were randomly allocated into groups and then treated with imidazole ketone erastin (IKE; 40 mg/kg, i.p., once every other day) in the absence or presence of liproxstatin-1 (10 mg/kg, i.p., once every other day) for 2 weeks. REF000313 ICD-11: 2C10.0 Pancreatic ductal adenocarcinoma CELL00160; CELL00212; CELL00120; CELL00013; CELL00045; CELL00048 CFPAC1; PANC2.03; PANC1; MIAPaCa2; A549; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis
unique00947 Elevation of mitochondrial LONP1 in erastin-induced ferroptosis of pancreatic cancer cell lines. Inhibition of LONP1 activates the Nrf2/Keap1 signal pathway and up-regulates the expression of GPX4, a key peroxidase in regulating ferroptosis. . . . Down regulation Driver Marker/Suppressor . REF000117 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00008 PANC1; BxPC3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Pathways in cancer (hsa05200) Cell ferroptosis; Cell proliferation
unique01102 High expression of the KAI1 (CD82) gene promoted the occurrence of ferroptosis in pancreatic cancer cells through its extensive effect on FPN and GPX4. KAI1induced ferroptosis did not significantly inhibit the proliferation of PC cells. . . . Up regulation Driver Marker/Suppressor . REF000343 ICD-11: 2C10 Pancreatic cancer CELL00013 PaCa-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01387 PTPMT1 is upregulated in pancreatic cancer and PTPMT1 inhibits ferroptosis by suppressing the expression of ACSL4 and upregulating SLC7A11 in Panc-1 cells, suggesting PTPMT1 might be a potential prognosis biomarker and therapeutic target in PDAC. . . . Up regulation Suppressor Suppressor . REF000638 ICD-11: 2C10 Pancreatic cancer CELL00120 Panc-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01714 We show that stearoyl-coA desaturase (SCD1) is the downstream of MEN1-mTOR signaling and oleic acid (OA), a metabolite of SCD1, recues the lipid peroxidation caused by MEN1 overexpression. The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, we find that BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pNETs that targets mTOR signaling. . . . Down regulation Driver Suppressor . REF000933 ICD-11: 2C10.1 Pancreatic neuroendocrine tumor CELL00276; CELL00258 BON-1; QGP-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01056 FBW7 (FBXW7) inhibited the expression of stearoyl-CoA desaturase (SCD1) via inhibiting nuclear receptor subfamily 4 group A member 1 (NR4A1). SCD1 was reported to inhibit both ferroptosis and apoptosis. And activating ferroptosis and apoptosis immensely increased gemcitabine sensitivity, which might provide strategies for the combination therapy for pancreatic cancer. . . . Up regulation Suppressor Suppressor . REF000275 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00222 PANC-1; SW1990 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01057 FBW7 (FBXW7) inhibited the expression of stearoyl-CoA desaturase (SCD1) via inhibiting nuclear receptor subfamily 4 group A member 1 (NR4A1). SCD1 was reported to inhibit both ferroptosis and apoptosis. And activating ferroptosis and apoptosis immensely increased gemcitabine sensitivity, which might provide strategies for the combination therapy for pancreatic cancer. . . . Down regulation Driver Suppressor . REF000275 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00222 PANC-1; SW1990 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique003861 The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115. Inducer Down regulation Down regulation Up regulation Suppressor . Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis. REF000522 ICD-11: 2C10.0 Pancreatic ductal adenocarcinoma CELL00013; CELL00048 MiaPaCa-2; HepG2 Ferroptosis (hsa04216) Cell ferroptosis
unique00386 The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115. Inducer Down regulation Down regulation Up regulation Suppressor . Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis. REF000522 ICD-11: 2C10.0 Pancreatic ductal adenocarcinoma CELL00013; CELL00048 MiaPaCa-2; HepG2 Ferroptosis (hsa04216) Cell ferroptosis
unique01036 Ferroptosis inducers (erastin, sorafenib, or sulfasalazine) activate ferritinophagy and AMPK phosphorylation, which consequently suppresses nuclear translocation of SREBP1, and inhibits the transcription of its direct target gene BCAT2. BCAT2 is a suppressor of ferroptosis by regulating intracellular glutamate levels in pancreatic ductal adenocarcinoma cells. Inducer Down regulation . . Suppressor . 1 x 106 BCAT2 overexpression and control Panc02 cancer cells were implanted subcutaneously into the right dorsal flanks of C57BL/6 mice (five mice per group), respectively. To investigate the role of combination sorafenib with sulfasalazine inducing ferroptosis, 1 x 106 Panc02 were implanted subcutaneously into the right dorsal flanks of C57BL/6 mice. To generate orthotopic tumors, forty C57BL/6 mice were surgically implanted with 1 x 106 H22 cells into left lobe of livers. REF000251 ICD-11: 2C10 Pancreatic ductal adenocarcinoma CELL00073; CELL00048; CELL00025; CELL00567; CELL00095; CELL00018 Aspc-1; HepG2; Panc02; H22; HT1080; SW480 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00919 Artesunate increased the mRNA and protein levels of GRP78 in a concentration-dependent manner in AsPC-1 and PaTU8988 cells. Knockdown GRP78 (HSPA5) enhanced artesunate-induced ferroptosis of pancreatic cancer cells in vitro and in vivo. Combining artesunate with GRP78 inhibition may be a novel maneuver for effective killing of KRAS mutant pancreatic ductal adenocarcinoma cells. Suppressor Up regulation . . Suppressor . AsPC-1 cells (1 x 106) with a control or GRP78 shRNA transfection were injected into right subcutaneous flank of nude mice (five mice per group). The nude mice were randomized into two groups and treated with DMSO or artesunate (30 mg/kg/i.p.), respectively. Artesunate was administered every two days. The tumor growth speed and volume were monitored every two days until the end point at day 35. All the tumor size and weight in the artesunate-treated groups were measured by using a caliper and an electronic balance. REF000086 ICD-11: 2C10 Pancreatic cancer CELL00233; CELL00073 PaTU8988; AsPC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00099 The antiviral drug zalcitabine can suppress pancreatic cancer cell growth through the induction of autophagy-dependent ferroptotic deathin vitroandin vivo. Mechanistically, these effects are dependent on mtDNA stress-induced activation of the CGAS-STING1 pathway. Inducer Up regulation . . Driver . NOD SCID mice (394) were purchased from Charles River Laboratories. Indicated wild-type or gene knockdown PANC1 cells (5 x 106 cells) were subcutaneously injected into the dorsal side of NOD SCID mice. At day 7, these mice were administrated with the indicated drug (zalcitabine [50 mg/kg, per day by i.p.], H-151 [750 nM per mouse, once every other day by i.p.], chloroquine [50 mg/kg, once every other day by i.p.], or liproxstatin-1 [10 mg/kg, once every other day by i.p.]) for 2 weeks. REF000150 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00047 PANC1; HTB-80 Ferroptosis (hsa04216); Autophagy (hsa04140); Cytosolic DNA-sensing pathway (hsa04623) Cell ferroptosis; Cell autophagy
unique00100 The antiviral drug zalcitabine can suppress pancreatic cancer cell growth through the induction of autophagy-dependent ferroptotic deathin vitroandin vivo. Mechanistically, these effects are dependent on mtDNA stress-induced activation of the CGAS-STING1 pathway. Inducer Up regulation . . Driver . NOD SCID mice (394) were purchased from Charles River Laboratories. Indicated wild-type or gene knockdown PANC1 cells (5 x 106 cells) were subcutaneously injected into the dorsal side of NOD SCID mice. At day 7, these mice were administrated with the indicated drug (zalcitabine [50 mg/kg, per day by i.p.], H-151 [750 nM per mouse, once every other day by i.p.], chloroquine [50 mg/kg, once every other day by i.p.], or liproxstatin-1 [10 mg/kg, once every other day by i.p.]) for 2 weeks. REF000150 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00047 PANC1; HTB-80 Ferroptosis (hsa04216); Autophagy (hsa04140); Cytosolic DNA-sensing pathway (hsa04623) Cell ferroptosis; Cell autophagy
unique00532 Dihydroartemisinin has anti-tumor effect in pancreatic cancer cells in vitro and in vivo. DHA treatment induced ferroptosis by increasing P53 and AOLX12 expression. Inducer Up regulation . . Driver . Six to eight-week-old female C57BL/6 mice were purchased from the Experimental Animal Center of Military Medical Sciences (Beijing, China). C57BL/6 mice were anesthetized and the tail of the pancreas was exposed. Panc 02 cells were resuspended in PBS at a concentration of 1 x 106 cells/0.1 ml and 50 ul cells were injected into the tail of the pancreas. Tumor-bearing mice were randomly divided into two groups (3 days after implantation). The control group was intraperitoneally injected 200 ul PBS daily for 10 days, and the DHA group was intraperitoneally injected with 100 mg/kg DHA daily for 10 days. The pancreatic tumors and spleens of the mice were collected for subsequent analysis. REF000739 ICD-11: 2C10 Pancreatic cancer CELL00025; CELL00120 Panc 02; Panc1 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00436 Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, atractylodin may induce ferroptosis in hepatocellular carcinoma cells by inhibiting the expression of GPX4 and FTL proteins, and up-regulating the expression of ACSL4 and TFR1 proteins. Inducer . Up regulation . . Driver . REF000584 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL10074 Huh7; Hccm Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique00553 A new seco-lupane triterpene derivative, compound21, was found to regulate cell growth through the cell cycle and ferroptosis, which in turn inhibited the proliferation, migration, and invasion of HepG2 cells. And it was found that compound 21 significantly upregulated ACSL4 protein expression and downregulated GPX4 protein expression. It has the potential to become an effective new drug for the treatment of hepatocellular carcinoma. Inducer . Up regulation . . Driver . REF000773 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048 HepG2 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00368 Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein responseinduced upregulation of CHAC1 expression. DHA also promoted the transcription of CHAC1. Inducer . Up regulation . . Marker/Driver A total of 32 male BALB/c nude mice (age, 6-8 weeks; weight, 18-20 g) were obtained from HFK Bioscience Co. Ltd. and housed in a specific pathogen-free facility. The mice were randomly divided into four groups (n = 8/group) and PLC cells were subcutaneously injected into the nude mice. When the xenografted tumors had grown to 80-100 mm3, half of the mice in each group were administered with 100 mg/kg DHA for 5 days/week by gavage. REF000506 ICD-11: 2C12 Hepatocellular carcinoma CELL00098; CELL00012; CELL00048; CELL00016; CELL00016 Hep3B; Huh7; HepG2; PLC; PLC/PRF/5 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00149 The saponin formosanin C (FC) is a novel natural ferroptosis inducer, which triggered a stronger ferroptosis in human hepatocellular carcinoma HepG2 cells containing a higher level of NCOA4 and a lower level of FTH1 compared to Hep3B cells. Inducer . Down regulation . . Marker/Suppressor . REF000205 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00098; CELL00048 Hep3B; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00435 Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, atractylodin may induce ferroptosis in hepatocellular carcinoma cells by inhibiting the expression of GPX4 and FTL proteins, and up-regulating the expression of ACSL4 and TFR1 proteins. Inducer . Down regulation . . Suppressor . REF000584 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL10074 Huh7; Hccm Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01540 PPARa activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF, suggesting that PPAR may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries in Hepatocellular carcinoma. . . . Up regulation Suppressor Suppressor C57BL/6J SPF mice were purchased from Huazhong Agricultural University Experimental Animal Center. Mice were given tertian intraperitoneal injections of either PBS (control) or dextriferron (500 mg/kg body weight) for 2 weeks and then sacrificed. Mice were given a daily intraperitoneal injection of either vehicle or ferrostatin-1 (Fer1, 1 mg/kg body weight) for 3 weeks before sacrificed. REF000758 ICD-11: 2C12 Hepatocellular carcinoma CELL00009 Hep16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00127 Solasonine increased lipid ROS levels in HepG2 cells by suppression of GPX4 and GSS. However, the use of a ferroptosis inhibitor reversed solasonine-induced ROS production and cell apoptosis. Taken together, solasonine promotes ferroptosis of hepatocellular carcinoma cells via GPX4-induced destruction of the glutathione redox system. Inducer . Down regulation . . Suppressor BALB/c nude mice aged 4-6 weeks, weighing 15~20 g, were purchased from Shanghai SLAC Laboratory Animal Co.,Ltd (Shanghai, China). Following acclimation, the right flank of each experimental mouse was subcutaneously injected with HepG2 cells (2 x 106) suspended in PBS (200 uL) and then randomly assigned to: (i) the control group and received no further treatment or (ii) the intervention group and received solasonine (50 mg/kg body weight) in an equal volume of PBS. Tumor volumes were measured every 5 days. After 30 days, the mice were sacrificed and the tumors were resected, weighed, and processed for histological analysis. REF000186 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00315 HepG2; HepRG Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00123 Auranofin/buthionine sulfoxime (BSO) and Erastin/BSO cotreatment alters redox homeostasis by increasing levels of Nrf2 and HO-1 and decreasing GPX4 levels. Targeting these two main ferroptotic pathways simultaneously can overcome chemotherapy resistance in hepatocellular carcinoma (HCC). Inducer . Down regulation . . Suppressor . REF000175 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00048 Huh7; HepG2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00434 Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, atractylodin may induce ferroptosis in hepatocellular carcinoma cells by inhibiting the expression of GPX4 and FTL proteins, and up-regulating the expression of ACSL4 and TFR1 proteins. Inducer . Down regulation . . Suppressor . REF000584 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL10074 Huh7; Hccm Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique00121 Auranofin/buthionine sulfoxime (BSO) and Erastin/BSO cotreatment alters redox homeostasis by increasing levels of Nrf2 and HO-1 and decreasing GPX4 levels. Targeting these two main ferroptotic pathways simultaneously can overcome chemotherapy resistance in hepatocellular carcinoma (HCC). Inducer . Down regulation . . Suppressor . REF000175 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00048 Huh7; HepG2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00122 Auranofin/buthionine sulfoxime (BSO) and Erastin/BSO cotreatment alters redox homeostasis by increasing levels of Nrf2 and HO-1 and decreasing GPX4 levels. Targeting these two main ferroptotic pathways simultaneously can overcome chemotherapy resistance in hepatocellular carcinoma (HCC). Inducer . Down regulation . . Suppressor . REF000175 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00048 Huh7; HepG2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00552 A new seco-lupane triterpene derivative, compound21, was found to regulate cell growth through the cell cycle and ferroptosis, which in turn inhibited the proliferation, migration, and invasion of HepG2 cells. And it was found that compound 21 significantly upregulated ACSL4 protein expression and downregulated GPX4 protein expression. It has the potential to become an effective new drug for the treatment of hepatocellular carcinoma. Inducer . Down regulation . . Suppressor . REF000773 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048 HepG2 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00411 2-pyridylhydrazone dithiocarbamate s-acetic acid (PdtaA) induced both apoptosis and cell cycle arrest. Notably, PdtaA also induced ferroptosis via downregulation of GPx4 and xCT in liver cancer cells. Autophagy inhibitor 3-methyladenin or genetic knockdown of NCOA4 was employed to inhibit ferritinophagy, which significantly neutralized the action of PdtaA in both apoptosis and ferroptosis. Inducer . Down regulation . . Suppressor . REF000559 ICD-11: 2C12 Hepatocellular carcinoma CELL00048 HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique01160 GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in hepatocellular carcinoma (HCC) cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment. . . . Down regulation Driver Suppressor Mice were divided into five groups as follows: WT + DMSO (control), WT + Sora, Gstz1-/-+DMSO, Gstz1-/-+Sora, and Gstz1-/-+Sora + RSL3. Each group included three male and three female mice. At 2 weeks of age, all mice were administered an intraperitoneal injection of diethylnitrosamine (DEN; Sigma, St. Louis, MO, USA) at a dose of 75 mg/kg. At the third week, the mice were intraperitoneally administered carbon tetrachloride (CCl4; Macklin, Shanghai, China) at 2 ml/kg twice a week for 12 weeks. In the WT + Sora and Gstz1-/-+Sora group, the mice at 22 weeks were administered intraperitoneally sorafenib (30 mg/kg) every 2 days for 4 weeks until euthanasia. In the Gstz1-/-+Sora + RSL3 group, in addition to sorafenib administration as described above, the mice were injected intraperitoneally with RSL3 (10 mg/kg) every 2 days for 4 weeks at the same weeks. REF000396 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00125; CELL00048; CELL00116; CELL00012 SK-Hep1; HepG2; SNU449; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01210 G6PD (glucose-6-phosphate dehydrogenase) was highly expressed in hepatocellular carcinoma and was associated with poor prognosis. G6PD promoted the proliferation, migration and invasion, as well as inhibited ferroptosis in HCC cells. G6PD inhibited ferroptosis inin HCC cells through POR. GPX4 was positively regulated by G6PD. . . . Up regulation Suppressor Marker/Suppressor Animal experiments were conducted under the guidance of Animal Management Regulations in Chongqing University. The tumor volume was calculated as follows: (length x width2)/2. After 24 days, the mice were killed and their tumors were collected, fixed and sectioned, stained by hematoxylin and eosin, and examined by a light microscopy for histological changes. REF000467 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00140; CELL00048; CELL00098; CELL00084 WRL68; HepG2; Hep3B217; SNU387 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01211 G6PD (glucose-6-phosphate dehydrogenase) was highly expressed in hepatocellular carcinoma and was associated with poor prognosis. G6PD promoted the proliferation, migration and invasion, as well as inhibited ferroptosis in HCC cells. G6PD inhibited ferroptosis inin HCC cells through POR. GPX4 was positively regulated by G6PD. . . . Down regulation Driver Marker/Suppressor Animal experiments were conducted under the guidance of Animal Management Regulations in Chongqing University. The tumor volume was calculated as follows: (length x width2)/2. After 24 days, the mice were killed and their tumors were collected, fixed and sectioned, stained by hematoxylin and eosin, and examined by a light microscopy for histological changes. REF000467 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00140; CELL00048; CELL00098; CELL00084 WRL68; HepG2; Hep3B217; SNU387 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01531 The expression of ferroptosis-related protein GPX4 decreased after HULC knockdown, and the GPX4 expression level was reversed when the inhibitor miR-3200-5p was added simultaneously. HULC was found to function as a ceRNA of miR-3200-5p, and miR-3200-5p regulates ferroptosis by targeting ATF4, resulting in the inhibition of proliferation and metastasis within hepatocellular carcinoma cells. . . . Up regulation Suppressor Suppressor . REF000747 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00017; CELL00291 SMMC-7721; BEL-7402 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01767 RBMS1 overexpression inhibited hepatocellular Carcinoma (HCC) cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. . . . Down regulation Driver Suppressor C57BL/6 mice (4- to 6-week-old male) were fed in a pathogen-free vivarium under standard conditions at the animal care facility at Sun Yat-sen University. Hepa 1-6 cells transduced with RBMS1 or GPX4 or circIDE overexpression lentiviral vectors were subcutaneously injected into the right flank of mice in 100 ul of sterile PBS. IVIS images were taken. REF000995 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00017; CELL00012; CELL00098; CELL00048; CELL00304 SMMC-7721; Huh7; Hep3B; HepG2; LO2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01678 JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating Cholangiocarcinoma tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. . . . Up regulation Suppressor Suppressor For the proliferation assays, HuCCT1 cells with linc00976 knockdown, linc00976 overexpression, and negative control were subcutaneously injected into BALB/c nude mice. The mice were weighed every week and euthanized 5 weeks after injection. Finally, tumors were dissected and weighed. For the proliferation assays, HuCCT1 cells with linc00976 knockdown, linc00976 overexpression, and negative control were subcutaneously injected into BALB/c nude mice. The mice were weighed every week and euthanized 5 weeks after injection. Finally, tumors were dissected and weighed. REF000889 ICD-11: 2C12 Cholangiocarcinoma CELL10027; CELL00097; CELL00303; CELL00305; CELL00256; CELL00284 HIBEC; HuCCT1; HCCC-9810; QBC939; HuH28; ; RBE Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01766 RBMS1 overexpression inhibited hepatocellular Carcinoma (HCC) cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. . . . Up regulation Suppressor Suppressor C57BL/6 mice (4- to 6-week-old male) were fed in a pathogen-free vivarium under standard conditions at the animal care facility at Sun Yat-sen University. Hepa 1-6 cells transduced with RBMS1 or GPX4 or circIDE overexpression lentiviral vectors were subcutaneously injected into the right flank of mice in 100 ul of sterile PBS. IVIS images were taken. REF000995 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00017; CELL00012; CELL00098; CELL00048; CELL00304 SMMC-7721; Huh7; Hep3B; HepG2; LO2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01009 CircIL4R acted as a miR-541-3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR-541-3p-induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in hepatocellular carcinoma via the miR-541-3p/GPX4 axis in vivo. . . . Down regulation Driver Suppressor The 5-week-old BALB/c male nude mice (n = 10) were purchased from the Animal Center of the Chinese Academy of Medical Sciences (Beijing, China). A number of 2 x 106 HuH-7 cells were transfected with lentiviral vectors containing sh-circIL4R or sh-NC to establish the stably expressed cell lines. Ten mice were subcutaneously injected with HuH-7 cells with sh-circIL4R or sh-NC (five mice per group), constructing the xenograft model of HCC in vivo. Every 5 days after injection, tumor size was measured by a vernier caliper and tumor volume (length x width2 x 0.5) was calculated. REF000213 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00273; CELL00012; CELL00299 THLE-2; HuH-7; HCCLM3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01680 JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating Cholangiocarcinoma tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. . . . Down regulation Driver Suppressor For the proliferation assays, HuCCT1 cells with linc00976 knockdown, linc00976 overexpression, and negative control were subcutaneously injected into BALB/c nude mice. The mice were weighed every week and euthanized 5 weeks after injection. Finally, tumors were dissected and weighed. For the proliferation assays, HuCCT1 cells with linc00976 knockdown, linc00976 overexpression, and negative control were subcutaneously injected into BALB/c nude mice. The mice were weighed every week and euthanized 5 weeks after injection. Finally, tumors were dissected and weighed. REF000889 ICD-11: 2C12 Cholangiocarcinoma CELL10027; CELL00097; CELL00303; CELL00305; CELL00256; CELL00284 HIBEC; HuCCT1; HCCC-9810; QBC939; HuH28; ; RBE Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01530 The expression of ferroptosis-related protein GPX4 decreased after HULC knockdown, and the GPX4 expression level was reversed when the inhibitor miR-3200-5p was added simultaneously. HULC was found to function as a ceRNA of miR-3200-5p, and miR-3200-5p regulates ferroptosis by targeting ATF4, resulting in the inhibition of proliferation and metastasis within hepatocellular carcinoma cells. . . . Down regulation Driver Suppressor . REF000747 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00017; CELL00291 SMMC-7721; BEL-7402 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01600 LncRNA HEPFAL promotes the ubiquitination of SLC7A11, resulting in a decrease in GSH production, which in turn affects the activity of GPX4 and ultimately leads to the occurrence of ferroptosis. And LncRNA HEPFAL has the potential as a target for the diagnosis and treatment of hepatocellular carcinoma. . . . Down regulation Driver Suppressor . REF000806 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00016 HEK293T; PLC/PRF/5 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01529 The expression of ferroptosis-related protein GPX4 decreased after HULC knockdown, and the GPX4 expression level was reversed when the inhibitor miR-3200-5p was added simultaneously. HULC was found to function as a ceRNA of miR-3200-5p, and miR-3200-5p regulates ferroptosis by targeting ATF4, resulting in the inhibition of proliferation and metastasis within hepatocellular carcinoma cells. . . . Up regulation Suppressor Suppressor . REF000747 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00017; CELL00291 SMMC-7721; BEL-7402 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01679 JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating Cholangiocarcinoma tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. . . . Up regulation Suppressor Suppressor For the proliferation assays, HuCCT1 cells with linc00976 knockdown, linc00976 overexpression, and negative control were subcutaneously injected into BALB/c nude mice. The mice were weighed every week and euthanized 5 weeks after injection. Finally, tumors were dissected and weighed. For the proliferation assays, HuCCT1 cells with linc00976 knockdown, linc00976 overexpression, and negative control were subcutaneously injected into BALB/c nude mice. The mice were weighed every week and euthanized 5 weeks after injection. Finally, tumors were dissected and weighed. REF000889 ICD-11: 2C12 Cholangiocarcinoma CELL10027; CELL00097; CELL00303; CELL00305; CELL00256; CELL00284 HIBEC; HuCCT1; HCCC-9810; QBC939; HuH28; ; RBE Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01008 CircIL4R acted as a miR-541-3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR-541-3p-induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in hepatocellular carcinoma via the miR-541-3p/GPX4 axis in vivo. . . . Up regulation Suppressor Suppressor The 5-week-old BALB/c male nude mice (n = 10) were purchased from the Animal Center of the Chinese Academy of Medical Sciences (Beijing, China). A number of 2 x 106 HuH-7 cells were transfected with lentiviral vectors containing sh-circIL4R or sh-NC to establish the stably expressed cell lines. Ten mice were subcutaneously injected with HuH-7 cells with sh-circIL4R or sh-NC (five mice per group), constructing the xenograft model of HCC in vivo. Every 5 days after injection, tumor size was measured by a vernier caliper and tumor volume (length x width2 x 0.5) was calculated. REF000213 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00273; CELL00012; CELL00299 THLE-2; HuH-7; HCCLM3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01765 RBMS1 overexpression inhibited Hepatocellular Carcinoma (HCC) cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. . . . Down regulation Driver Suppressor C57BL/6 mice (4- to 6-week-old male) were fed in a pathogen-free vivarium under standard conditions at the animal care facility at Sun Yat-sen University. Hepa 1-6 cells transduced with RBMS1 or GPX4 or circIDE overexpression lentiviral vectors were subcutaneously injected into the right flank of mice in 100 ul of sterile PBS. IVIS images were taken. REF000995 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00017; CELL00012; CELL00098; CELL00048; CELL00304 SMMC-7721; Huh7; Hep3B; HepG2; LO2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00007 The study demonstrated that haloperidol strengthened sorafenib-induced ferroptosis in Hepatocellular carcinoma cell lines for the first time. During ferroptosis, haloperidol substantially increased the cellular levels of Fe2+, GSH and lipid peroxidation. Additionally, haloperidol induced the expression of HO-1. Inducer . Up regulation . . Driver/Suppressor . REF000021 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012 Hep G2; Huh-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00556 Eupalinolide B (EB) exerts anti-proliferative activity in hepatic carcinoma by blocking cell cycle arrest at S phase and inducing ferroptosis mediated by endoplasmic reticulum (ER) stress, as well as HO-1 activation. And EB has the ability to inhibit cell proliferation and migration in hepatic carcinoma. Inducer . Up regulation . . Driver Four-week-old nude mice (BALB/c) were used, and they were housed for 1 week in a specific pathogen-free (SPF) environment before experimentation. Each mouse received subcutaneous injections of 1 x 106 SMMC-7721 or HCCLM3 cells in 200 uL phosphate-buffered saline (PBS) into both flanks. One group was intraperitoneally injected every two days with EB at 25 or 50 mg/mouse body weight, for a total of 3 weeks. As a control, DMSO was used in another group. Tumor size was measured to calculate tumor volume, and mouse body weights were monitored every two days. REF000787 ICD-11: 2C12 Hepatocellular carcinoma CELL00017; CELL00299 SMMC-7721; HCCLM3 MAPK signaling pathway (hsa04010); Ferroptosis (hsa04216) Cell ferroptosis; Cell migration; Cell proliferation
unique00148 The saponin formosanin C (FC) is a novel natural ferroptosis inducer, which triggered a stronger ferroptosis in human hepatocellular carcinoma HepG2 cells containing a higher level of NCOA4 and a lower level of FTH1 compared to Hep3B cells. Inducer . Up regulation . . Driver . REF000205 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00098; CELL00048 Hep3B; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00412 2-pyridylhydrazone dithiocarbamate s-acetic acid (PdtaA) induced both apoptosis and cell cycle arrest. Notably, PdtaA also induced ferroptosis via downregulation of GPx4 and xCT in liver cancer cells. Autophagy inhibitor 3-methyladenin or genetic knockdown of NCOA4 was employed to inhibit ferritinophagy, which significantly neutralized the action of PdtaA in both apoptosis and ferroptosis. Inducer . Up regulation . . Driver . REF000559 ICD-11: 2C12 Hepatocellular carcinoma CELL00048 HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00459 Knockdown of NCOA4 significantly attenuated the regulatory effect of 2-pyridylhydrazone dithiocarbamate s-acetic acid (PdtaA) on related proteins which highlighted that the strength of ferritinophagic flux (NCOA4/ferritin) was a driving force in determination of the status of EMT and ferroptosis. PdtaA treatment resulted in ferritinophagy that triggered ROS production in liver cancer cells. Inducer . Up regulation . . Driver . REF000610 ICD-11: 2C12 Hepatocellular carcinoma CELL00048 HepG2 Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis
unique01723 PTBP1 mediates ferroptosis in liver cancer cells by regulating NCOA4 translation.In vivoexperiments reconfirmed the role of the PTBP1NCOA4axis in a xenograft transplantation model. It was observed that the mean tumor weight increased afterPTBP1knockout. . . . Up regulation Driver Driver A total of eight male BALB/c nude mice (4-5 weeks old; weight, 13-18 g) were obtained from Beijing Vital River Laboratories. The mice were randomly divided into the following two groups: The NC + SF and sh-PTBP1 + SF groups. Hep3B cells (2 x 106) were subcutaneously injected into the right flank of each mouse. The mice were injected intraperitoneally with SF (10 mg/kg) every 2 days for 2 weeks. REF000944 ICD-11: 2C12 Hepatocellular carcinoma CELL00012; CELL00098; CELL00048; CELL00057 Huh-7; Hep3B; HepG2; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01797 Sorafenib is a potent inducer of ferroptosis used to manage hepatocellular carcinoma (HCC). Nrf2 inhibition by Camptothecin improves sorafenib's sensitivity and reduces sorafenib's resistance via the augmentation of sorafenib's ferroptosis action. Inducer . Down regulation . . Marker/Suppressor . REF001026 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012 HepG2; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01133 QSOX1 disrupts redox homoeostasis and sensitizes hepatocellular carcinoma cells to oxidative stress by inhibiting activation of the master antioxidant transcription factor NRF2. Mechanistically, QSOX1 restrains EGF-induced EGFR activation by promoting ubiquitination-mediated degradation of EGFR and accelerating its intracellular endosomal trafficking, leading to suppression of NRF2 activity. . . . Down regulation Driver Marker/Suppressor Male 6-week-old BALB/c nude mice were purchased from Charles River Company (Shanghai, China). For subcutaneous mouse model, 5 x106 MHCC97H vector control cells or MHCC97H/QSOX1 cells were implanted into right flanks subcutaneously. At the 7th day following implantation, the mice bear with MHCC97H vector control cells or MHCC97H/QSOX1 cells respectively were randomly separated into two groups: one group were treated with vehicle (0.9% NaCl i.p., once every other day) and another group sorafenib (10 mg/kg i.p., once every other day) for two weeks. REF000366 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00285; CELL00098 MHCC97H; Hep3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01159 GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in hepatocellular carcinoma (HCC) cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment. . . . Down regulation Driver Marker/Suppressor Mice were divided into five groups as follows: WT + DMSO (control), WT + Sora, Gstz1-/-+DMSO, Gstz1-/-+Sora, and Gstz1-/-+Sora + RSL3. Each group included three male and three female mice. At 2 weeks of age, all mice were administered an intraperitoneal injection of diethylnitrosamine (DEN; Sigma, St. Louis, MO, USA) at a dose of 75 mg/kg. At the third week, the mice were intraperitoneally administered carbon tetrachloride (CCl4; Macklin, Shanghai, China) at 2 ml/kg twice a week for 12 weeks. In the WT + Sora and Gstz1-/-+Sora group, the mice at 22 weeks were administered intraperitoneally sorafenib (30 mg/kg) every 2 days for 4 weeks until euthanasia. In the Gstz1-/-+Sora + RSL3 group, in addition to sorafenib administration as described above, the mice were injected intraperitoneally with RSL3 (10 mg/kg) every 2 days for 4 weeks at the same weeks. REF000396 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00125; CELL00048; CELL00116; CELL00012 SK-Hep1; HepG2; SNU449; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01476 FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response in Hepatocellular Carcinoma Cells, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib. . . . Up regulation Suppressor Marker/Suppressor Mice weighing between 20 and 23 g were selected and 5 x 106 Hep-G2 cells were subcutaneously injected into their backs. The mice were subsequently divided into the following four groups: control (n = 5), FNDC5 overexpressing (n = 5), FNDC5 overexpressing followed by treatment with the PI3K inhibitor LY294002 (MCE, China), and FNDC5 knockdown (n = 5). Seven days after cell injection, sorafenib (30 mg/kg) was administered to all mice via intraperitoneal injection every alternate day for 4 weeks. The mice in the third group were intraperitoneally injected with LY294002 (25 mg/kg) diluted with DMSO twice a week for 4 weeks. REF000707 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012 HepG-2; Huh7 PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique01475 FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response in Hepatocellular Carcinoma Cells, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib. . . . Up regulation Suppressor Marker/Suppressor Mice weighing between 20 and 23 g were selected and 5 x 106 Hep-G2 cells were subcutaneously injected into their backs. The mice were subsequently divided into the following four groups: control (n = 5), FNDC5 overexpressing (n = 5), FNDC5 overexpressing followed by treatment with the PI3K inhibitor LY294002 (MCE, China), and FNDC5 knockdown (n = 5). Seven days after cell injection, sorafenib (30 mg/kg) was administered to all mice via intraperitoneal injection every alternate day for 4 weeks. The mice in the third group were intraperitoneally injected with LY294002 (25 mg/kg) diluted with DMSO twice a week for 4 weeks. REF000707 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012 HepG-2; Huh7 PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique01716 The disruption of PCSK9 inhibits the anti-ferroptosis p62-Keap1-Nrf2 pathway, one could speculate that a combination therapy of anti-PCSK9 with sorafenib would alleviate drug resistance and improve prognosis. We provide strong evidence supporting the drug repositioning of anti-PCSK9 approaches to treat hepatocellular carcinoma. . . . Up regulation Suppressor Marker/Suppressor Zebrafish were maintained at 28 and in light cycle conditions (12 h). The Casper mutant fish line was purchased from the Zebrafish International Resource Center (ZIRC). For zebrafish xenotransplantation, 48 hours post-fertilization (hpf) zebrafish embryos were dechorionated and anesthetized in egg water solution containing 0.04 mg/mL tricaine (Sigma-Aldrich, St. Louis, MO, USA) before human cell injection. Approximately 200 to 500 fluorescent cells were injected (Eppendorf Femtojet microinjector) into the ducts of Cuvier of each embryo, and the zebrafish were maintained in 0.3X Danieaus solution for 1 h at 28 . After confirmation of a visible cell mass at the injection site, the zebrafish were transferred to a 24-well plate in 500 uL of a 0.3X Danieaus solution incubator and maintained at 34 . The zebrafish with already formed metastasis at 1 hour post-injection (hpi) were discarded. REF000936 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00048; CELL00279 Huh7; HepG2; Huh6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01721 The combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in hepatocellular carcinoma, providing a potential therapeutic strategy for overcoming sorafenib resistance. . . . Down regulation Driver Marker/Suppressor Age-matched male BALB/c nude mice (4-6 weeks old) were used for the orthotopic mouse model. Cohorts of mice were randomized into different treatment groups. 4 x 106 tumor cells were suspended in a 50 ul PBS/Matrigel (356234, BD Biosciences) mixture (1:1 (v/v) ratio) for each group of mice and injected into the left liver lobes by surgical implantation. REF000940 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00016; CELL00125 HepG2; PLC/PRF/5; SK-Hep1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01477 FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response in Hepatocellular Carcinoma Cells, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib. . . . Up regulation Suppressor Marker/Suppressor Mice weighing between 20 and 23 g were selected and 5 x 106 Hep-G2 cells were subcutaneously injected into their backs. The mice were subsequently divided into the following four groups: control (n = 5), FNDC5 overexpressing (n = 5), FNDC5 overexpressing followed by treatment with the PI3K inhibitor LY294002 (MCE, China), and FNDC5 knockdown (n = 5). Seven days after cell injection, sorafenib (30 mg/kg) was administered to all mice via intraperitoneal injection every alternate day for 4 weeks. The mice in the third group were intraperitoneally injected with LY294002 (25 mg/kg) diluted with DMSO twice a week for 4 weeks. REF000707 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012 HepG-2; Huh7 PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique01064 Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 (SLC16A1) inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. Suppressor . Up regulation . . Suppressor Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable. REF000282 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00029; CELL00057; CELL00304; CELL00048; CELL00098; CELL00012 CAF; 293T; 7702; HepG2; Hep3B; Huh-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique01522 MiR-142-3p promoted HBV-infected M1-type macrophage ferroptosis through SLC3A2, affecting the production of GSH, MDA, and Fe2+and accelerating the development of hepatocellular carcinoma (HCC). Inhibition of miR-142-3p or overexpression of SLC3A2 reversed ferroptosis and inhibited the proliferation, migration, and invasion of HCC cells. . . . Down regulation Driver Suppressor . REF000738 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00038 HepG2; THP-1 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00682 PNO1 inhibits autophagy-mediated ferroptosis via GSH metabolic reprogramming as demonstrated above. We also demonstrated that PNO1 inhibition repressed SLC7A11 through p53 to promote ferroptosis. These observations suggested that sh-PNO1 could be a new target in hepatocellular carcinoma therapy. . . . Up regulation Suppressor Suppressor Xenograft mouse model experiments were used male BALB/c nude mice (4 weeks old) purchased from SPF Biotechnology (Beijing, China). Each mouse was injected 5 x 106 tumor cells at the volume of 100 uL into the subcutaneous tissue. The tumor volume and weight of the mice was observed every 2 days. Mice were monitored daily and the tumor volume calculated according to the equation volume = length x width2 x 1/2. REF000905 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057 HEK293T Autophagy (hsa04140); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique00144 Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment. Inducer . Down regulation . . Suppressor A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm3, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day. REF000202 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00063; CELL00116 HepG2; SNU-182; SNU-449 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00378 Necrostatin-1 potentiated sulfasalazine-induced expression of SLC7A11, a catalytic subunit of system xc- in these cells. And necrostatin-1 Prevents Ferroptosis in a RIPK1- and IDO-Independent Manner in Hepatocellular Carcinoma. Suppressor . Up regulation . . Suppressor . REF000514 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00125 Huh7; SK-HEP-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01323 ABCC5 increased intracellular glutathione (GSH) and attenuated lipid peroxidation accumulation by stabilizing SLC7A11 protein, which inhibited ferroptosis. Additionally, the inhibition of ABCC5 enhanced the anti-cancer activity of sorafenib in hepatocellular carcinoma. . . . Up regulation Suppressor Suppressor All animal experiments were carried out with the approval of the Southern Medical University Animal Care and Use Committee in accordance with the guidelines for the ethical treatment of animals. Nude nu/nu mice were maintained in a barrier facility in racks filtered with a high-efficiency particulate air filter. The animals were fed an autoclaved laboratory rodent diet. The mice in this study were purchased from the Experimental Animal Centre of Southern Medical University, which is certified by the Guangdong Provincial Bureau of Science. REF000577 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00048; CELL00125 HuH7; HepG2; Sk-Hep-1 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00991 TGF-B1 represses xCT (SLC7A11) expression via Smad3 activation and enhances lipid peroxidation in hepatocellular carcinoma cells with an early TGF-B1 signature, which would benefit from the targeting of GPX4. . . . Down regulation Driver Suppressor . REF000184 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00016; CELL00048; CELL00012; CELL00084; CELL00116; CELL00343; CELL00125; CELL00279 PLC/PRF/5; HepG2; Huh7; SNU387; SNU449; SNU475; SK-Hep1; Huh6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01300 In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. . . . Up regulation Suppressor Suppressor SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (106 in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks. REF000550 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00061; CELL00095; CELL00012; CELL00175; CELL00098 HEK293T; SNU398; HT1080; Huh7; HLE; Hep3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis
unique01298 In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. . . . Up regulation Suppressor Suppressor SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (106 in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks. REF000550 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00061; CELL00095; CELL00012; CELL00175; CELL00098 HEK293T; SNU398; HT1080; Huh7; HLE; Hep3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis
unique01067 DAZAP1 knockdown by small interfering RNA markedly inhibited hepatocellular carcinoma (HCC) cell proliferation, migration and invasion. At the mechanistic level, DAZAP1 was identified as a potent inhibitor of ferroptosis and an efficient binding partner of SLC7A11 mRNA. . . . Up regulation Suppressor Suppressor Male BALB/c nude mice (4-5 weeks, 14-18 g) were purchased from Vital River Laboratories (Beijing, China). We randomly (random number grouping method) divided the mice into five groups: the blank group, the DMSO group, the SF group, the SF + sh-NC group and the SF + sh-DAZAP1 group. For SF-intervention mice, we dissolved 10 mg/kg of SF into 0.2 ml DMSO and injected the mixture intraperitoneally every other day for two weeks. 1 x 107 cells (with or without lentivirus) suspended in 500 ul of ice-cold PBS were subcutaneously injected into the left flank of mice. REF000289 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00017; CELL00098; CELL00291; CELL00012; CELL00304 HepG2; SMMC-7721; Hep3B; Bel-7402; Huh7; L02 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01277 METTL14 induced m6A modification at 5'UTR of SLC7A11 mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Importantly, ectopic expression of SLC7A11 strongly blocked METTL14-induced tumour-suppressive effect in hypoxic hepatocellular carcinoma. . . . Down regulation Driver Suppressor The BALB/C nude mice were obtained from Shanghai SLAC Laboratory Animal Co., Ltd. 5 x 105 stable SLC7A11-knockdown HCCLM3 cells or SLC7A11-vector cells were injected subcutaneously into BALB/C nude mice. After 5 weeks, mice were killed, and tumour photograph was detected with photography. In the other animal work, 5 x 105 stable METTL14-vector HCCLM3 cells, SLC7A11-Overexpression cells or SLC7A11-R298P cells were injected subcutaneously into BALB/C nude mice. REF000527 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00048; CELL00017; CELL00299; CELL00285; CELL00016; CELL00291; CELL00304 Huh7; HepG2; 7721; HCCLM3; MHCC97H; PLC/PRF/5; Bel7402; L02 Fatty acid metabolism (hsa01212); Glutamate metabolism (hsa00250); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00683 PNO1 inhibits autophagy-mediated ferroptosis via GSH metabolic reprogramming as demonstrated above. We also demonstrated that PNO1 inhibition repressed SLC7A11 through p53 to promote ferroptosis. These observations suggested that sh-PNO1 could be a new target in Hepatocellular carcinoma therapy. . . . Up regulation Suppressor Suppressor Xenograft mouse model experiments were used male BALB/c nude mice (4 weeks old) purchased from SPF Biotechnology (Beijing, China). Each mouse was injected 5 x 106 tumor cells at the volume of 100 uL into the subcutaneous tissue. The tumor volume and weight of the mice was observed every 2 days. Mice were monitored daily and the tumor volume calculated according to the equation volume = length x width2 x 1/2. REF000905 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057 HEK293T Autophagy (hsa04140); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique01299 In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. . . . Up regulation Suppressor Suppressor SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (106 in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks. REF000550 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00061; CELL00095; CELL00012; CELL00175; CELL00098 HEK293T; SNU398; HT1080; Huh7; HLE; Hep3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis
unique01757 Overexpression of AKR1C3 protected against ferroptosis in hepatocellular carcinoma (HCC) cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC. . . . Up regulation Suppressor Suppressor To generate murine subcutaneous tumors, 2 x 106 HCC cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached approximately 100 mm3 at day 15, mice were randomly allocated into groups and treated with erastin or sorafenib for 2 weeks. REF000983 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00098; CELL00057; CELL00012; CELL00285; CELL10075 Hep3B; HEK-293T; Huh7; MHCC-97H; HCC-LY10 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation; Cell metastasis
unique01758 Overexpression of AKR1C3 protected against ferroptosis in hepatocellular carcinoma (HCC) cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC. . . . Up regulation Suppressor Suppressor To generate murine subcutaneous tumors, 2 x 106 HCC cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached approximately 100 mm3 at day 15, mice were randomly allocated into groups and treated with erastin or sorafenib for 2 weeks. REF000983 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00098; CELL00057; CELL00012; CELL00285; CELL10075 Hep3B; HEK-293T; Huh7; MHCC-97H; HCC-LY10 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation; Cell metastasis
unique01173 Circ0097009 acts as a competing endogenous RNA to regulate the expression of SLC7A11, a key regulator of cancer cell ferroptosis, by sponging miR-1261 in hepatocellular cancer. Circ0097009 may be used as a diagnostic biomarker for HCC and as a potential target for HCC therapy. . . . Down regulation Driver Suppressor Four-week-old female BALB/c nude mice were subcutaneously inoculated with 2 x 106 cells (5 mice per group). Intratumoral injection (40 uL of si-circ0097009 or negative control siRNA) was administered every 4 days. Mice were sacrificed, and tumor weights were measured after 4 weeks. To establish lung metastases, HepG2 cells were treated with 20 umol/L si-circ0097009. After 48 hours, cells (1 x 105) were intravenously injected into the tail veins of mice (6 mice per group). REF000407 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00304; CELL00048; CELL00291; CELL00285 LO2; HepG2; BEL-7402; MHCC-97H Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion; Cell metastasis
unique01599 LncRNA HEPFAL promotes the ubiquitination of SLC7A11, resulting in a decrease in GSH production, which in turn affects the activity of GPX4 and ultimately leads to the occurrence of ferroptosis. And LncRNA HEPFAL has the potential as a target for the diagnosis and treatment of hepatocellular carcinoma. . . . Down regulation Driver Suppressor . REF000806 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00016 HEK293T; PLC/PRF/5 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01172 Circ0097009 acts as a competing endogenous RNA to regulate the expression of SLC7A11, a key regulator of cancer cell ferroptosis, by sponging miR-1261 in hepatocellular cancer. Circ0097009 may be used as a diagnostic biomarker for Hepatocellular carcinoma and as a potential target for HCC therapy. . . . Up regulation Suppressor Suppressor Four-week-old female BALB/c nude mice were subcutaneously inoculated with 2 x 106 cells (5 mice per group). Intratumoral injection (40 uL of si-circ0097009 or negative control siRNA) was administered every 4 days. Mice were sacrificed, and tumor weights were measured after 4 weeks. To establish lung metastases, HepG2 cells were treated with 20 umol/L si-circ0097009. After 48 hours, cells (1 x 105) were intravenously injected into the tail veins of mice (6 mice per group). REF000407 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00304; CELL00048; CELL00291; CELL00285 LO2; HepG2; BEL-7402; MHCC-97H Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion; Cell metastasis
unique01541 PPARa activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF (TF), suggesting that PPAR may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries in Hepatocellular carcinomaHepatocellular carcinoma. . . . Down regulation Suppressor Marker/Suppressor/Driver C57BL/6J SPF mice were purchased from Huazhong Agricultural University Experimental Animal Center. Mice were given tertian intraperitoneal injections of either PBS (control) or dextriferron (500 mg/kg body weight) for 2 weeks and then sacrificed. Mice were given a daily intraperitoneal injection of either vehicle or ferrostatin-1 (Fer1, 1 mg/kg body weight) for 3 weeks before sacrificed. REF000758 ICD-11: 2C12 Hepatocellular carcinoma CELL00009 Hep16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00437 Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, atractylodin may induce ferroptosis in hepatocellular carcinoma cells by inhibiting the expression of GPX4 and FTL proteins, and up-regulating the expression of ACSL4 and TFR1 proteins. Inducer . Up regulation . . Marker/Suppressor/Driver . REF000584 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL10074 Huh7; Hccm Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01208 The effects by which TrCP-mediated ubiquitination and followed degradation of TFRC to decline labile iron are critical for TRIB2 to desensitize liver cancer cells to ferroptosis. Appropriate reduction of TRIB2 function might be beneficial for patients bearing liver cancer because it will definitely sensitize ferroptosis-based therapy. . . . Down regulation Suppressor Marker/Suppressor/Driver . REF000465 ICD-11: 2C12 Hepatocellular carcinoma CELL00474; CELL00291; CELL00017; CELL00125; CELL00048; CELL00057 Bel-7404; Bel-7402; SMMC-7721; SK-Hep1; HepG2; HEK-293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01617 Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced Hepatocellular carcinoma cell death. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis. Inducer Down regulation . . . Suppressor Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed. REF000831 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00304; CELL00048; CELL00098; CELL00017; CELL00012; CELL00291; CELL00057 LO2; HepG2; Hep3B; SMMC-7721; Huh7; Bel-7402; 293T Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01682 LncFAL reduced ferroptosis vulnerability by directly binding to ferroptosis suppressor protein 1 (FSP1) and competitively abolishing Trim69-dependent FSP1 polyubiquitination degradation. Collectively, our results provide a clinically promising demonstration that HDLBP stabilizes lncFAL, which mediates a FSP1-dependent anti-ferroptosis mechanism in Hepatocellular carcinoma. . . . Up regulation Suppressor Suppressor Six-week-old female BALB/c nude mice were purchased from Byrness Weil Biotechnology Ltd. (Chengdu, China) and housed in a specific pathogen-free environment with a 12-h light/dark cycle and controlled temperature and humidity, and food and water were provided ad libitum. Three million designated treated PLC5 cells were collected and injected subcutaneously into mice. At least 4 mice were used in each group in each experiment. Once the tumours reached a mean volume of 200 mm3, the mice were treated intraperitoneally with sorafenib every 3 days. The mice were then euthanized at the indicated time after injection. Each tumour was dissected, fixed with 4% formaldehyde, and embedded in paraffin. The tumour growth was monitored weekly by calliper measurements. REF000894 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012; CELL00016; CELL00084; CELL00098 HepG2; Huh7; PLC5; SUN387; Hep3B Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01681 LncFAL reduced ferroptosis vulnerability by directly binding to ferroptosis suppressor protein 1 (FSP1) and competitively abolishing Trim69-dependent FSP1 polyubiquitination degradation. Collectively, our results provide a clinically promising demonstration that HDLBP stabilizes lncFAL, which mediates a FSP1-dependent anti-ferroptosis mechanism in Hepatocellular carcinoma. . . . Up regulation Suppressor Suppressor Six-week-old female BALB/c nude mice were purchased from Byrness Weil Biotechnology Ltd. (Chengdu, China) and housed in a specific pathogen-free environment with a 12-h light/dark cycle and controlled temperature and humidity, and food and water were provided ad libitum. Three million designated treated PLC5 cells were collected and injected subcutaneously into mice. At least 4 mice were used in each group in each experiment. Once the tumours reached a mean volume of 200 mm3, the mice were treated intraperitoneally with sorafenib every 3 days. The mice were then euthanized at the indicated time after injection. Each tumour was dissected, fixed with 4% formaldehyde, and embedded in paraffin. The tumour growth was monitored weekly by calliper measurements. REF000894 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012; CELL00016; CELL00084; CELL00098 HepG2; Huh7; PLC5; SUN387; Hep3B Fatty acid metabolism (hsa01212) Cell ferroptosis
unique003871 The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115. Inducer Down regulation Down regulation Up regulation Suppressor . Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis. REF000522 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00013; CELL00048 MiaPaCa-2; HepG2 Ferroptosis (hsa04216) Cell ferroptosis
unique00387 The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115. Inducer Down regulation Down regulation Up regulation Suppressor . Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis. REF000522 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00013; CELL00048 MiaPaCa-2; HepG2 Ferroptosis (hsa04216) Cell ferroptosis
unique00604 Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced hepatocellular carcinoma cell death. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis. Inducer Down regulation . . Suppressor . Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 106) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm3, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed. REF000831 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00304; CELL00048; CELL00098; CELL00017; CELL00012; CELL00291; CELL00057 LO2; HepG2; Hep3B; SMMC-7721; Huh7; Bel-7402; 293T Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00973 Erastin and RSL3 suppress ceruloplasmin expression in hepatocellular carcinoma cells. CP suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. The suppression function of ceruloplasmin in erastin- and RSL3-induced ferroptosis is dependent on FPN. Inducer Down regulation . . Suppressor . . REF000160 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00098; CELL00057 HepG2; Hep3B; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00972 Erastin and RSL3 suppress ceruloplasmin expression in hepatocellular carcinoma cells. CP suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. The suppression function of ceruloplasmin in erastin- and RSL3-induced ferroptosis is dependent on FPN. Inducer Down regulation . . Suppressor . . REF000160 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00098; CELL00057 HepG2; Hep3B; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01001 Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment. Inducer Up regulation . . Driver . A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm3, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day. REF000202 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00063; CELL00116 HepG2; SNU-182; SNU-449 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00240 Heteronemin is an effective agent against hepatocellular carcinoma that induces HCC cell apoptosis and ferroptosis by inducing intracellular ROS formation and the p38 (MAPK14)/JNK MAPK signaling pathway, revealing the potent MAPK-mediated crosstalk mechanism between apoptosis and ferroptosis. Inducer Up regulation . . Driver . . REF000307 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00308; CELL00332 HA22T/VGH; HA59T/VGH Fatty acid metabolism (hsa01212); Apoptosis (hsa04210); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00938 Erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. GABPB1 and GABPB1-AS1 are attractive therapeutic targets for hepatocellular carcinoma. Inducer Down regulation . . Suppressor . . REF000108 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012; CELL00098 HepG2; Huh7; Hep3B Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00939 Erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. GABPB1 and GABPB1-AS1 are attractive therapeutic targets for hepatocellular carcinoma. Inducer Down regulation . . Suppressor . . REF000108 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012; CELL00098 HepG2; Huh7; Hep3B Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01002 Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment. Inducer Up regulation . . Driver . A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm3, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day. REF000202 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00063; CELL00116 HepG2; SNU-182; SNU-449 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01720 The combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in hepatocellular carcinoma, providing a potential therapeutic strategy for overcoming sorafenib resistance. Inducer Down regulation . . Suppressor . Age-matched male BALB/c nude mice (4-6 weeks old) were used for the orthotopic mouse model. Cohorts of mice were randomized into different treatment groups. 4 x 106 tumor cells were suspended in a 50 ul PBS/Matrigel (356234, BD Biosciences) mixture (1:1 (v/v) ratio) for each group of mice and injected into the left liver lobes by surgical implantation. REF000940 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00016; CELL00125 HepG2; PLC/PRF/5; SK-Hep1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00937 Erastin upregulated the lncRNA GABPB1-AS1, which downregulated GABPB1 protein levels by blocking GABPB1 translation, leading to the downregulation of the gene encoding Peroxiredoxin-5 (PRDX5) peroxidase and the eventual suppression of the cellular antioxidant capacity. GABPB1 and GABPB1-AS1 are attractive therapeutic targets for hepatocellular carcinoma. Inducer Up regulation . . Driver . . REF000108 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00012; CELL00098 HepG2; Huh7; Hep3B Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01152 Expression levels of SIRT3 in patients with gallbladder cancer were lower than those in the adjacent normal tissue. Silence of SIRT3 gene also suppressed AKT-dependent ferroptosis, an iron-dependent and lipid peroxide-mediated cell death. Blockade of AKT activity in sh-SIRT3 cells induced ACSL4 expression that drives ferroptosis, and inhibited epithelial-mesenchymal (EMT) markers and invasive activity. . . . Up regulation Driver Driver Forty male BALB/cnude mice (4 weeks old, 15-16 g) were purchased from the Shanghai Laboratory Animal Center (Shanghai, China) and divided into eight groups. Cells (1.0 x 106) were subcutaneously injected into the leftaxillaof nude mice. REF000387 ICD-11: 2C13 Gallbladder cancer CELL00482; CELL00520; CELL00427; CELL00426 GBC-SD; EH-GB1; OCUG-1; NOZ Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00984 In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1). . . . Up regulation Suppressor Marker/Suppressor . REF000178 ICD-11: 2C13 Gallbladder cancer CELL00489; CELL00482 H69; GBC-SD Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00983 In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1). . . . Up regulation Suppressor Driver/Suppressor . REF000178 ICD-11: 2C13 Gallbladder cancer CELL00489; CELL00482 H69; GBC-SD Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00985 In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1). . . . Up regulation Suppressor Suppressor . REF000178 ICD-11: 2C13 Gallbladder cancer CELL00489; CELL00482 H69; GBC-SD Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00982 In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1). . . . Up regulation Suppressor Marker/Suppressor . REF000178 ICD-11: 2C13 Gallbladder cancer CELL00489; CELL00482 H69; GBC-SD Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01690 After IGF2BP3 overexpression, expression levels and mRNA stabilities of these anti-ferroptotic factors were successfully sustained. Notably, significant correlations between SLC3A2, ACSL3, and IGF2BP3 were revealed in clinical Lung adenocarcinoma specimens, further establishing the essential role of IGF2BP3 in desensitizing ferroptosis. Inducing ferroptosis has been gradually accepted as an alternative strategy to treat tumors. . . . Up regulation Suppressor Suppressor Igf2bp3-/- mice were generated by Cyagen Biosciences (Guangzhou,China). Mettl3-/- mice were obtained as described in our previous study. H1299 cells with or without IGF2BP3 overexpression were digested and adjusted to a density of 5 x 106 cells/200 uL. Next, 200 uL of cells were injected into the right armpit of each 4-6-week-old athymic nude mouse (Jiesijie, Shanghai, China). The weight and tumor size of nude mice were measured. Each group contained five mice. After 2 weeks, mice were injected daily with dimethyl sulfoxide (DMSO, Beyotime Biotechnology, Shanghai, China) with or without imidazole ketone erastin (IKE, 50 mg/kg, MedChemExpress, Monmouth, NJ, USA) or rigosertib (RIG, 250 mg/kg, Selleck, Houston, TX, USA). REF000908 ICD-11: 2C25.0 Lung adenocarcinoma CELL00076; CELL00056; CELL00222; CELL00087 BEAS-2B; H1299; SW1990; HCT116 Ferroptosis (hsa04216) Cell ferroptosis
unique00257 Curcumin induced ferroptosis via activating autophagy in non-small-cell lung cancer (NSCLC), which enhanced the therapeutic effect of NSCLC. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Inducer . Up regulation . . Driver Female C57BL/6 mice (14-18 g) were purchased from SiPeiFu (Beijing) Biotechnology. C57BL/6 mice were subcutaneously injected with a total of 6 x 105 Lewis lung carcinomas (LLC) cells on the left flank. Four days after LLC inoculation, the mice were randomly divided into two groups of five. The vehicle control and curcumin groups were given sodium carboxymethyl cellulose (CMC) or curcumin (100 mg/kg/day) by intraperitoneal injection for 15 days. REF000345 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056 A549; H1299 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell proliferation; Cell autophagy
unique00580 d-borneol in combination with cisplatin induced ferroptosisviaNCOA4-mediated ferritinophagy and also increased the expression levels of ACSL4, regulated PCBP2 and PRNP to promote the conversion of Fe3+to Fe2+, reduced the activity or expression of antioxidants enzymes (GSH and HO-1), and induced ROS accumulation and thereby promoted ferroptosis. In addition, activation of autophagy inhibited progression of the EMT and increased sensitivity to cisplatin in cisplatin-resistant lung cancer cells. Inducer . Up regulation . . Driver Male Balb/c nude mice (4-week-old) were purchased from SPF (Beijing) biotechnology co., LTD and maintained in the Experimental Animal Research Center of Chengdu University of TCM. After 1 week of adaptable feeding, H460/CDDP cells (5 x 106 cells in 0.1 ml phosphate-buffered saline) were subcutaneously injected into the right dorsal flank to establish tumor model. When the tumor volume grows to 100 mm3, the tumor-bearing mice were randomly divided into the following four treatment groups: a control group (Con, n = 6): intraperitoneal injection of saline once a day; vehicle group (Vehicle, n = 6): intragastric administration of 2% tween and intraperitoneal injection of saline; d-borneol low-dose group (Bor-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day; d-borneol high-dose group (Bor-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day; CDDP group (CDDP, n = 6): intraperitoneal injection of cisplatin (3 mg/kg) every two days; a low-dose combination treatment group (C+B-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days; a high-dose combination treatment group (C+B-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days. We usually first orally gavage d-borneol, and then inject cisplatin intraperitoneally half an hour later. After 14 days treatment, the samples were obtained from the mice for the further experiments. REF000809 ICD-11: 2C25.Y Non-small cell lung cancer CELL00507 H460/CDDP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell autophagy
unique01447 SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy. . . . Down regulation Suppressor Driver An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 106 cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. REF000683 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01424 Intracellular cir93FABP3 interactions are critical to upregulate FABP3 to reduce global AA via reactions with taurine. The product of AA and taurine (i.e., NAT) prevents AA incorporation into the plasma membrane, thus further reducing the opportunity for PUFA peroxidation in the membrane. NAT reduces ACSL4, LPCAT3 and PLTP. Exosome and cir93 are critical to desensitize lung adenocarcinoma to ferroptosis. . . . Down regulation Suppressor Driver All athymic nude mice (6-week-old) were purchased from Jiesijie (Shanghai, China). To generate routine cell-derived xenograft (CDX) mouse models, established LUAD cells (initial 5 x 106) were subcutaneously injected into the bilateral dorsal flank of athymic nude mice. To generate H1975/A549 cell-implanted intrapulmonary LUAD mice, athymic nude mice were intrapulmonarily injected with cells (5 x 106) under anesthesia and then intranasally administered adeno-associated virus 5 (AAV5) particles (2 x 1012 viral particles/mL, Genomeditech, Shanghai, China) 3 weeks later. To generate patient-derived xenograft (PDX) mouse models, fresh LUAD tissues with a size of 2-3 mm3 were subcutaneously implanted into athymic nude mice. After successful passage, the PDX mice were used for further studies. REF000667 ICD-11: 2C25.0 Lung adenocarcinoma CELL00287; CELL00317; CELL00195; CELL00201; CELL00045; CELL00056; CELL00342 H1650; PC9; H1975; H358; A549; H1299; MRC-5; W138 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00691 CircSCN8A represses cell proliferation and metastasis in NSCLC by regulating the miR-1290/ACSL4 axis to induce ferroptosis. Thus, circSCN8A may represent a promising therapeutic target against NSCLC. . . . Down regulation Suppressor Driver Male BALB/c nude mice (3-4 weeks, 16-20 g) were purchased from Vital River Laboratory (Beijing, China) and housed under standard conditions. After acclimatization for one week, mice were randomly divided into two groups (n = 6/group). A549 cells infected with lentivirus circSCN8A (Lv-circSNC8A) or control (Lv-vector) were selected in the presence of puromycin (1 ug/ml). A549 cells (7 x 106) with Lv-circSNC8A or Lv-vector were suspended in 100 uL PBS and respectively injected into each mouse at the right flank. REF000915 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056; CELL00022; CELL00148; CELL00076 A549; H1299; NCI-H520; SK-MES-1; BEAS-2B Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01125 NEAT1 regulated levels of ACSL4 and proteins related to the ferroptosis and classical apoptosis pathways. And NEAT1 regulates ferroptosis and ferroptosis sensitivity, with the latter depending on ACSL4, suggesting that targeting NEAT1 or ACSL4 may be a viable therapeutic approach to the treatment of non-small-cell lung cancer (NSCLC). . . . Down regulation Suppressor Driver . REF000359 ICD-11: 2C25.Y Non-small cell lung cancer CELL00085; CELL00045; CELL00195; CELL00148; CELL00309 HBE; A549; NCI-H1975; SK-MES-1; PLA-801D Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00690 CircSCN8A represses cell proliferation and metastasis in NSCLC by regulating the miR-1290/ACSL4 axis to induce ferroptosis. Thus, circSCN8A may represent a promising therapeutic target against NSCLC. . . . Up regulation Driver Driver Male BALB/c nude mice (3-4 weeks, 16-20 g) were purchased from Vital River Laboratory (Beijing, China) and housed under standard conditions. After acclimatization for one week, mice were randomly divided into two groups (n = 6/group). A549 cells infected with lentivirus circSCN8A (Lv-circSNC8A) or control (Lv-vector) were selected in the presence of puromycin (1 ug/ml). A549 cells (7 x 106) with Lv-circSNC8A or Lv-vector were suspended in 100 uL PBS and respectively injected into each mouse at the right flank. REF000915 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056; CELL00022; CELL00148; CELL00076 A549; H1299; NCI-H520; SK-MES-1; BEAS-2B Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01422 Intracellular cir93 FABP3 interactions are critical to upregulate FABP3 to reduce global AA via reactions with taurine. The product of AA and taurine (i.e., NAT) prevents AA incorporation into the plasma membrane, thus further reducing the opportunity for PUFA peroxidation in the membrane. NAT reduces ACSL4, LPCAT3 and PLTP. Exosome and cir93 are critical to desensitize lung adenocarcinoma to ferroptosis. . . . Down regulation Suppressor Driver All athymic nude mice (6-week-old) were purchased from Jiesijie (Shanghai, China). To generate routine cell-derived xenograft (CDX) mouse models, established LUAD cells (initial 5 x 106) were subcutaneously injected into the bilateral dorsal flank of athymic nude mice. To generate H1975/A549 cell-implanted intrapulmonary LUAD mice, athymic nude mice were intrapulmonarily injected with cells (5 x 106) under anesthesia and then intranasally administered adeno-associated virus 5 (AAV5) particles (2 x 1012 viral particles/mL, Genomeditech, Shanghai, China) 3 weeks later. To generate patient-derived xenograft (PDX) mouse models, fresh LUAD tissues with a size of 2-3 mm3 were subcutaneously implanted into athymic nude mice. After successful passage, the PDX mice were used for further studies. REF000667 ICD-11: 2C25.0 Lung adenocarcinoma CELL00287; CELL00317; CELL00195; CELL00201; CELL00045; CELL00056; CELL00342 H1650; PC9; H1975; H358; A549; H1299; MRC-5; W138 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01462 The study found GSEC, CISD1, ATP5MC3, and PGD to be upregulated, with miRNA-101-3p downregulated, in the setting of lung adenocarcinoma (LUAD). Immunohistochemical analysis revealed CISD1, ATP5MC3, and PGD overexpression in LUAD tissue samples; CISD1 knockdown was noted to significantly inhibit LUAD proliferation and migration. . . . Down regulation Suppressor Driver/Suppressor . REF000693 ICD-11: 2C25.0 Lung adenocarcinoma CELL00076; CELL00045; CELL00195 BEAS-2B; A549; H1975 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell infiltration
unique00506 The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRAS mutant non-small-cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Marker/Suppressor Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5. REF000696 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00509 The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRAS mutant non-small-cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Marker/Suppressor Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5. REF000696 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00853 NFS1 suppression induced TFRC expression and repressed FTH1 and cytoplasmic aconitase activity. Suppression of NFS1 cooperates with inhibition of cysteine transport to trigger ferroptosis in vitro and slow tumour growth. Therefore, lung adenocarcinomas select for expression of a pathway that confers resistance to high oxygen tension and protects cells from undergoing ferroptosis in response to oxidative damage. . . . Down regulation Driver Marker/Suppressor Tumours were initiated in 4-8-week-old female NOD. CB17 Scid/J mice. Orthotopically in the mouse mammary gland, by implantation of 500,000 cells in 25 ul 33% Matrigel into the fourth mouse mammary fat pad; subcutaneously, by injection of 500,000 cells in 100 ul 33% Matrigel into the left or right flank of the mouse; via tail vein by injection of 500,000 cells in 150 ul RPMI into the mouse tail vein; and via intratracheal instillation by instilling 200,000 cells in 50 ul 2 mM EDTA as described. Cancer cells were transduced with viral shRNAs, selected for 3 days with puromycin, and allowed to recover for one day before introduction into mice. For experiments comparing subcutaneous and lung tumour formation, shRNA transduced cells were prepared at the same time and injected on the same day. Animals were imaged by IVIS (Perkin Elmer) 15 min following injection subcutaneously into the neck scruff with XenoLight d-Luciferin (165 mg per kg body weight, Perkin Elmer). Average luminescence was quantified per mouse from equal sized bins covering the mouse thorax. For experiments in which tumour growth was measured upon drug treatment, MDA-MB-231 cells, implanted as described above, were allowed to form palpable tumours (~4 mm diameter) and mice were sorted into treatment groups as described below. PEG-Cyst(e)inase was delivered via intraperitoneal injection at 50 mg per kg body weight every 3 days, SSA was delivered by daily intraperitoneal injection at 250 mg per kg body weight, and BSO was delivered in the drinking water at 20 mM with 5 mg ml-1 sucralose. REF000032 ICD-11: 2C25.0 Lung adenocarcinoma CELL00462; CELL00005; CELL00226; CELL00377; CELL00045; CELL00197; CELL00205; CELL00021; CELL00384; CELL00015; CELL00148; CELL00200; CELL00153 MCF10DCIS.com; MDA-MB-231; SW900; NCI-H196; A549; NCI-H2170; NCI-H647; 786-O; A498 NCI-H838; NCI-H460; SK-MES-1; NCI-H322 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00926 Metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc-heterodimerization partner), at both the messenger RNA and protein levels in Lung adenocarcinoma. . . . Down regulation Driver Suppressor To generate tumor xenograft models, 5 x 106 MTDH WT and KO MDA-MB-231 cells were injected into the second and fifth mammary fat pads (both sides, total four sites) of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, Jackson Laboratories, Bar Harbor, ME) immunodeficient female mice. To study the metastasis from this orthotopic mouse model, tumor volumes were allowed to grow to ~1000 mm3, after which livers were resected to examine incidence as well as tumor burden of liver metastasis. REF000093 ICD-11: 2C25 Lung adenocarcinoma CELL00045; CELL00195; CELL00362; CELL00361; CELL00181; CELL00333; CELL00123; CELL00089; CELL00024; CELL00005; CELL00002; CELL00421 A549; H1975; DMS53; DMS273; KLE; AN3CA; RL95; Hec1A; Ishikawa; MDA-MB-231; MCF-7; Hec50 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00023 Dihydroartemisinin (DAT) can augment GPX4 inhibition-induced ferroptosis in a cohort of cancer cells that are otherwise highly resistant to ferroptosis. Collectively, artemisinin compounds can sensitize cells to ferroptosis by regulating cellular iron homeostasis in Lung mucoepidermoid carcinoma. Inducer . Down regulation . . Suppressor GPX4 iKO H292 cells were inoculated by injecting 3 x 106 cells in 0.1 mL PBS subcutaneously in the right flank of six- to eight-week-old female athymic nude Foxn1nu/Foxn1 mice (Envigo, East Millstone, NJ, USA). Following inoculation, the mice were monitored until they have fully recovered and are moving. Mice were randomly allocated into their respective groups (non-blinded). Tumor growth was monitored regularly via external caliper measurements. REF000068 ICD-11: 2C25 Lung mucoepidermoid carcinoma CELL00117; CELL00087; CELL00562; CELL00018; CELL00111; CELL00002; CELL00095 NCI-H292; HCT116; HT29; SW480; MDA-MB-453; MCF7; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell proliferation; Cell autophagy
unique00192 The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Suppressor Briefly, when tumours on transplanted nude mice reached around 100 mm3, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed. REF000254 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015; CELL00306 A549; NCI-460; SPC-A-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00505 The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Suppressor Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5. REF000696 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00508 The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Suppressor Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5. REF000696 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00555 Capsaicin inhibited the proliferation of A549 and NCI-H23 cells and induced ferroptosis by inactivating SLC7A11/GPX4 signaling. Capsaicin could be used as a potential anticancer agent in the treatment of non-small cell lung cancer (NSCLC). Inducer . Down regulation . . Suppressor . REF000778 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00199 A549; NCI-H23 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00788 Dihydroartemisinin (DHA) treatment decreased the levels of GPX4, DHA significantly induced apoptosis and ferroptosis in a dose-dependent manner and exhibited high cellular toxicity on A549-GR (non-small cell lung cancer) cells when combined with gefitinib. Inducer . Down regulation . . Suppressor . REF001009 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00236; CELL00195 A549; HCC827; H1975 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00837 In non-small-cell lung cancer (NSCLC) cells, active MAPK signaling downstream of active EGFR can sensitize cells to ferroptosis upon cystine depletion. Sensitization involves both impaired detoxification of lipid peroxides, due to reduced expression of GPX4, and generation of hydrogen peroxide, via NOX4. . . . Down regulation Driver Suppressor 2.5 x 105 NCI-H1650 cells were inoculated 1:1 in Matrigel: PBS (100 mL) by subcutaneous injection into eight non-obese diabetic (NOD) severe combined immunodeficiency (SCID) gamma male mice. Tumors were allowed to engraft and grow for 30 days (tumor volume averaged ~200 mm3) and mice treated by intraperitoneal (i.p.) injection with 100 mg/kg cyst(e)inase or 100 mg/kg heat-inactivated cyst(e)inase (n = 4 ea.) on day 30, with a second dose given on day 33. Mice were necropsied 24 hr after the second dose. REF000019 ICD-11: 2C25.Y Non-small cell lung cancer CELL00433; CELL00287 hTERT-HME; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01104 MiR-324-3p was able to reduce the viability and increase death of cisplatin-resistant A549 cells. Its function may be exerted through its direct binding to GPX4, a key regulator of ferroptosis. MiR-324-3p could serve as a potential target in the treatment of non small cell lung cancer (NSCLC). . . . Down regulation Driver Suppressor . REF000347 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00325 A549; A549/DDP Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01146 It was observed that CREB (CREB1, CREB3 and CREB5) suppressed lipid peroxidation by binding the promoter region of glutathione peroxidase 4 (GPX4), and this binding could be enhanced by E1A binding protein P300 (EP300). Therefore, targeting this CREB/EP300/GPX4 axis may provide new strategies for treating lung adenocarcinoma. . . . Up regulation Suppressor Suppressor . REF000380 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00342; CELL00139; CELL00148; CELL00198; CELL00201; CELL00045; CELL00056; CELL00287 293T; MRC-5; WI-38; MES-1; H226; H358; A549; H1299; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01147 It was observed that CREB (CREB1, CREB3 and CREB5) suppressed lipid peroxidation by binding the promoter region of glutathione peroxidase 4 (GPX4), and this binding could be enhanced by E1A binding protein P300 (EP300). Therefore, targeting this CREB/EP300/GPX4 axis may provide new strategies for treating lung adenocarcinoma. . . . Up regulation Suppressor Suppressor . REF000380 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00342; CELL00139; CELL00148; CELL00198; CELL00201; CELL00045; CELL00056; CELL00287 293T; MRC-5; WI-38; MES-1; H226; H358; A549; H1299; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01148 It was observed that CREB (CREB1, CREB3 and CREB5) suppressed lipid peroxidation by binding the promoter region of glutathione peroxidase 4 (GPX4), and this binding could be enhanced by E1A binding protein P300 (EP300). Therefore, targeting this CREB/EP300/GPX4 axis may provide new strategies for treating lung adenocarcinoma. . . . Up regulation Suppressor Suppressor . REF000380 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00342; CELL00139; CELL00148; CELL00198; CELL00201; CELL00045; CELL00056; CELL00287 293T; MRC-5; WI-38; MES-1; H226; H358; A549; H1299; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01182 Orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. Inducer . Down regulation . . Suppressor C57BL/6 mice were anesthetized, and 5 x 105 LLC cells were implanted subcutaneously into the right flank. Five days post-implant, mice were randomized and assigned into two groups and treated with orlistat (10 mg/kg, intraperitoneal injection) or PBS daily for 14 days. The tumor volume was measured twice a week with a caliper, and the tumor volume was calculated according to the formula ((length x width2 )/2). REF000421 ICD-11: 2C25 Lung cancer CELL00056; CELL00045; CELL00560 H1299; A549; LLC Fatty acid metabolism (hsa01212); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique01281 It was identified that circDTL exerts its oncogenic effects via the circDTL/miR-1287-5p/GPX4 axis and GPX4 inhibits both ferroptosis and apoptosis. Finally, silencing of circDTL promoted the sensitivity of non-small cell lung cancer cells to chemotherapeutic agents and inhibited the growth of tumors in vivo. . . . Up regulation Suppressor Suppressor The Shanghai SLAC Animal Center (Shanghai, China) provided 4-6-week-old BALB/c male nude mice, which were kept according to the standards for the use and care of laboratory animals. A total of 1 x 107 NSCLC cells infected with shRNA were injected subcutaneously into the left flank of nude mice (3 per group). Every 3 days, the tumor volume was measured. REF000533 ICD-11: 2C25.Y Non-small cell lung cancer CELL00076; CELL00199; CELL00204; CELL00317; CELL00045 BEAS-2B; H23; H522; PC9; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01282 It was identified that circDTL exerts its oncogenic effects via the circDTL/miR-1287-5p/GPX4 axis and GPX4 inhibits both ferroptosis and apoptosis. Finally, silencing of circDTL promoted the sensitivity of non-small cell lung cancer cells to chemotherapeutic agents and inhibited the growth of tumors in vivo. . . . Down regulation Driver Suppressor The Shanghai SLAC Animal Center (Shanghai, China) provided 4-6-week-old BALB/c male nude mice, which were kept according to the standards for the use and care of laboratory animals. A total of 1 x 107 NSCLC cells infected with shRNA were injected subcutaneously into the left flank of nude mice (3 per group). Every 3 days, the tumor volume was measured. REF000533 ICD-11: 2C25.Y Non-small cell lung cancer CELL00076; CELL00199; CELL00204; CELL00317; CELL00045 BEAS-2B; H23; H522; PC9; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00191 The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Suppressor Briefly, when tumours on transplanted nude mice reached around 100 mm3, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed. REF000254 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015; CELL00306 A549; NCI-460; SPC-A-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00507 The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells. Inducer . Up regulation . . Driver Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5. REF000696 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00510 The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells. Inducer . Up regulation . . Driver Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5. REF000696 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00603 S-3'-hydroxy-7', 2', 4'-trimethoxyisoxane (ShtIX) caused ferroptosis in Non-small cell lung cancer (NSCLC) cells, and inhibiting the Nrf2/HO-1 pathway can considerably exacerbate the effect of ShtIX-induced ferroptosis. Inducer . Down regulation . . Suppressor When tumor volumes in xenograft nude mice reached an average of roughly 100 mm3, the mice were randomly divided into 3 groups of 6 mice each: control, ShtIX, and ShtIX + Fer-1. The treated group received ShtIX or ShtIX combined with Fer-1 injections into the tail vein of the mice every three days for 7 times, whereas the control group received saline. Every four days, the volume and weight of the tumors were measured. As soon as the test was completed, the nude mice were slaughtered, and the tumor tissues were retrieved. The in vivo experiments were approved by the Animal Care and Use Committee of Hainan Medical College and following the animal rules. REF000830 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01423 Intracellular cir93-FABP3 interactions are critical to upregulate FABP3 to reduce global AA via reactions with taurine. The product of AA and taurine (i.e., NAT) prevents AA incorporation into the plasma membrane, thus further reducing the opportunity for PUFA peroxidation in the membrane. NAT reduces ACSL4, LPCAT3 and PLTP. Exosome and cir93 are critical to desensitize lung adenocarcinoma to ferroptosis. . . . Down regulation Suppressor Driver All athymic nude mice (6-week-old) were purchased from Jiesijie (Shanghai, China). To generate routine cell-derived xenograft (CDX) mouse models, established LUAD cells (initial 5 x 106) were subcutaneously injected into the bilateral dorsal flank of athymic nude mice. To generate H1975/A549 cell-implanted intrapulmonary LUAD mice, athymic nude mice were intrapulmonarily injected with cells (5 x 106) under anesthesia and then intranasally administered adeno-associated virus 5 (AAV5) particles (2 x 1012 viral particles/mL, Genomeditech, Shanghai, China) 3 weeks later. To generate patient-derived xenograft (PDX) mouse models, fresh LUAD tissues with a size of 2-3 mm3 were subcutaneously implanted into athymic nude mice. After successful passage, the PDX mice were used for further studies. REF000667 ICD-11: 2C25.0 Lung adenocarcinoma CELL00287; CELL00317; CELL00195; CELL00201; CELL00045; CELL00056; CELL00342 H1650; PC9; H1975; H358; A549; H1299; MRC-5; W138 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01425 Intracellular cir93-FABP3 interactions are critical to upregulate FABP3 to reduce global AA via reactions with taurine. The product of AA and taurine (i.e., NAT) prevents AA incorporation into the plasma membrane, thus further reducing the opportunity for PUFA peroxidation in the membrane. NAT reduces ACSL4, LPCAT3 and PLTP. Exosome and cir93 are critical to desensitize lung adenocarcinoma to ferroptosis. . . . Down regulation Suppressor Driver All athymic nude mice (6-week-old) were purchased from Jiesijie (Shanghai, China). To generate routine cell-derived xenograft (CDX) mouse models, established LUAD cells (initial 5 x 106) were subcutaneously injected into the bilateral dorsal flank of athymic nude mice. To generate H1975/A549 cell-implanted intrapulmonary LUAD mice, athymic nude mice were intrapulmonarily injected with cells (5 x 106) under anesthesia and then intranasally administered adeno-associated virus 5 (AAV5) particles (2 x 1012 viral particles/mL, Genomeditech, Shanghai, China) 3 weeks later. To generate patient-derived xenograft (PDX) mouse models, fresh LUAD tissues with a size of 2-3 mm3 were subcutaneously implanted into athymic nude mice. After successful passage, the PDX mice were used for further studies. REF000667 ICD-11: 2C25.0 Lung adenocarcinoma CELL00287; CELL00317; CELL00195; CELL00201; CELL00045; CELL00056; CELL00342 H1650; PC9; H1975; H358; A549; H1299; MRC-5; W138 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00836 In non-small-cell lung cancer (NSCLC) cells, active MAPK signaling downstream of active EGFR can sensitize cells to ferroptosis upon cystine depletion. Sensitization involves both impaired detoxification of lipid peroxides, due to reduced expression of GPX4, and generation of hydrogen peroxide, via NOX4. . . . Up regulation Driver Driver 2.5 x 105 NCI-H1650 cells were inoculated 1:1 in Matrigel: PBS (100 mL) by subcutaneous injection into eight non-obese diabetic (NOD) severe combined immunodeficiency (SCID) gamma male mice. Tumors were allowed to engraft and grow for 30 days (tumor volume averaged ~200 mm3) and mice treated by intraperitoneal (i.p.) injection with 100 mg/kg cyst(e)inase or 100 mg/kg heat-inactivated cyst(e)inase (n = 4 ea.) on day 30, with a second dose given on day 33. Mice were necropsied 24 hr after the second dose. REF000019 ICD-11: 2C25.Y Non-small cell lung cancer CELL00433; CELL00287 hTERT-HME; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00845 ARF (CDKN2A) expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses in lung large cell carcinoma cell lines. . . . Down regulation Driver Marker/Suppressor Pooled stable cell line was derived from H1299 tet-on ARF cells by transfecting either empty vector or vector overexpressing NRF2. Cells were selected by G418 (1 mg /ml) for 2 weeks and then re-transfected the same vectors again. After additional treatment with or without doxycycline (1.0 mg/ml) for 60 h, 1.0 x 106 of cells were then mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) and injected subcutaneously into nude mice (NU/NU, Charles River). The mice were fed with the food containing doxycycline hyclate (Harlan, 625 mg/kg) or control food. REF000027 ICD-11: 2C25 Lung large cell carcinoma CELL00056; CELL00004; CELL00134; CELL00055 H1299; 293; SaoS2; U2OS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00846 ARF (CDKN2A) expression sensitizes cells to ferroptosis in a p53-independent manner while ARF depletion induces NRF2 activation and promotes cancer cell survival in response to oxidative stress. NRF2 is a major target of p53-independent tumor suppression by ARF and also suggest that the ARF-NRF2 interaction acts as a new checkpoint for oxidative stress responses in Lung adenocarcinomaLung adenocarcinoma. . . . Down regulation Driver Marker/Suppressor Pooled stable cell line was derived from H1299 tet-on ARF cells by transfecting either empty vector or vector overexpressing NRF2. Cells were selected by G418 (1 mg /ml) for 2 weeks and then re-transfected the same vectors again. After additional treatment with or without doxycycline (1.0 mg/ml) for 60 h, 1.0 x 106 of cells were then mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) and injected subcutaneously into nude mice (NU/NU, Charles River). The mice were fed with the food containing doxycycline hyclate (Harlan, 625 mg/kg) or control food. REF000027 ICD-11: 2C25 Lung large cell carcinoma CELL00056; CELL00004; CELL00134; CELL00055 H1299; 293; SaoS2; U2OS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00071 The potential mechanism by which sorafenib and erastin induced ferroptosis in cisplatin (CDDP)-resistant non-small cell lung cancer (NSCLC) cells may be associated with inhibition of the expression of the Nrf2 downstream target gene xCT. Inducer . Down regulation . . Marker/Suppressor A total of 60 BALB/c-nu/nu nude mice (male; age, 4-6 weeks; weight, 16-22 g) were obtained from the Shanghai Laboratory Animal Co., Ltd. N5CP cells (5 x 106) were suspended in 200 ul DMEM and Matrigel mixture at a ratio of 1:1. Subsequently, the mixture was injected subcutaneously into the upper right flank of 20 nude mice. After 10 days, the mice were randomly divided into four groups and were treated with CDDP (5 mg/kg/2 days), erastin (10 mg/kg/2 days), sorafenib (10 mg/kg/2 days) or PBS by intraperitoneal injection. Two days after the third injection, the mice were sacrificed and tumours were carefully removed. For the combination experiment, CDDP (1 mg/kg) and erastin (5 mg/kg) or sorafenib (3 mg/kg) were also injected three times. REF000121 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056 A549; NCI-H1299 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00072 The potential mechanism by which sorafenib and erastin induced ferroptosis in cisplatin (CDDP)-resistant non-small cell lung cancer (NSCLC) cells may be associated with inhibition of the expression of the Nrf2 downstream target gene xCT. Inducer . Down regulation . . Marker/Suppressor A total of 60 BALB/c-nu/nu nude mice (male; age, 4-6 weeks; weight, 16-22 g) were obtained from the Shanghai Laboratory Animal Co., Ltd. N5CP cells (5 x 106) were suspended in 200 ul DMEM and Matrigel mixture at a ratio of 1:1. Subsequently, the mixture was injected subcutaneously into the upper right flank of 20 nude mice. After 10 days, the mice were randomly divided into four groups and were treated with CDDP (5 mg/kg/2 days), erastin (10 mg/kg/2 days), sorafenib (10 mg/kg/2 days) or PBS by intraperitoneal injection. Two days after the third injection, the mice were sacrificed and tumours were carefully removed. For the combination experiment, CDDP (1 mg/kg) and erastin (5 mg/kg) or sorafenib (3 mg/kg) were also injected three times. REF000121 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056 A549; NCI-H1299 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00190 The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Marker/Suppressor Briefly, when tumours on transplanted nude mice reached around 100 mm3, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed. REF000254 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015; CELL00306 A549; NCI-460; SPC-A-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00602 S-3'-hydroxy-7', 2', 4'-trimethoxyisoxane (ShtIX) caused ferroptosis in Non-small cell lung cancer (NSCLC) cells, and inhibiting the Nrf2/HO-1 pathway can considerably exacerbate the effect of ShtIX-induced ferroptosis. Inducer . Down regulation . . Marker/Suppressor When tumor volumes in xenograft nude mice reached an average of roughly 100 mm3, the mice were randomly divided into 3 groups of 6 mice each: control, ShtIX, and ShtIX + Fer-1. The treated group received ShtIX or ShtIX combined with Fer-1 injections into the tail vein of the mice every three days for 7 times, whereas the control group received saline. Every four days, the volume and weight of the tumors were measured. As soon as the test was completed, the nude mice were slaughtered, and the tumor tissues were retrieved. The in vivo experiments were approved by the Animal Care and Use Committee of Hainan Medical College and following the animal rules. REF000830 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015 A549; H460 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00733 Manoalide (MA) induces ferroptosis by suppressing the NRF2-SLC7A11 axis and mitochondrial Ca2+overload induced-FTH1 pathways to promote the sensitivity of osimertinib-resistant lung cancer cells to osimertinib. Suppressor . Down regulation . . Marker/Suppressor The LSL-KrasG12D mouse model was obtained from the Jackson Laboratory (Sacramento, CA). Adeno-Cre (Genechem, Shanghai, China) was introduced into the trachea of mice at a dose of 1.25 x 1011 PFU in a total volume of 50 uL. Tumor tissues from 12-week post-infection mice were washed with cold PBS, cut into small pieces, and washed with DMEM/F12 (containing 1 x Glutamine, 10 mM HEPES, and antibiotics), digested with collagenase I and IV for 0.5-1 h at 37. After washing twice with DMEM/F12 and centrifugation (500 g, 5 min), the dissociated cells were seeded into growth factor-reduced matrigel (Corning, #356237) at 37 for 30 min. REF000955 ICD-11: 2C25 Lung cancer CELL00045; CELL00249; CELL00236; CELL00317 A549; H157; HCC827; PC9 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01020 Previous findings indicated that metallothionein 1D pseudogene (MT1DP), a long noncoding RNA (lncRNA), functioned to aggravate oxidative stress by repressing antioxidation. RNA pulldown assay and dual-luciferase reporter assay confirmed that MT1DP modulated the expression of NRF2 via stabilizing miR-365a-3p. In conclusion, MT1DP sensitized non-small cell lung cancer (NSCLC) cells to erastin-induced ferroptosis by regulating the miR-365a-3p/NRF2 signaling pathway. . . . Down regulation Driver Marker/Suppressor A total of 6 x 106 A549 cells were subcutaneously injected into the right flank of the athymic BALB/c nude mice (aged 4 weeks, weight 12-16 g; Vital River, Beijing, China). Once tumors reached about 80 mm3, the mice were randomly divided into four groups. Mice were treated with 50 uM/kg erastin by intraperitoneal injection every 2 days for eight times. Tumor size was measured. REF000230 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056 A549; H1299 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01021 Previous findings indicated that metallothionein 1D pseudogene (MT1DP), a long noncoding RNA (lncRNA), functioned to aggravate oxidative stress by repressing antioxidation. RNA pulldown assay and dual-luciferase reporter assay confirmed that MT1DP modulated the expression of NRF2 via stabilizing miR-365a-3p. In conclusion, MT1DP sensitized non-small cell lung cancer (NSCLC) cells to erastin-induced ferroptosis by regulating the miR-365a-3p/NRF2 signaling pathway. . . . Down regulation Driver Marker/Suppressor A total of 6 x 106 A549 cells were subcutaneously injected into the right flank of the athymic BALB/c nude mice (aged 4 weeks, weight 12-16 g; Vital River, Beijing, China). Once tumors reached about 80 mm3, the mice were randomly divided into four groups. Mice were treated with 50 uM/kg erastin by intraperitoneal injection every 2 days for eight times. Tumor size was measured. REF000230 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00056 A549; H1299 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01077 USP11 is highly expressed in patients with non-small cell lung cancer (NSCLC) and positively correlated with NRF2 expression. Together, USP11 stabilizes NRF2 and is thus an important player in cell proliferation and ferroptosis. . . . Up regulation Suppressor Marker/Suppressor . REF000311 ICD-11: 2C25.Y Non-small cell lung cancer CELL00057; CELL00056; CELL00087; CELL00045; CELL00049 HEK 293T; H1299; HCT116; A549; Hela Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01304 MIB1 may function as a positive regulator of ferroptosis through targeted degradation of the master antioxidant transcription factor NRF2 and sensitizes lung cancer cells to ferroptosis. . . . Down regulation Driver Marker/Suppressor . REF000553 ICD-11: 2C25 Lung cancer CELL00045; CELL00005; CELL00057 A549; MDA-MB-231; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Cell adhesion molecules (hsa04514); Notch signaling pathway (hsa04330) Cell ferroptosis
unique00914 The autophagy-mediated degradation of ARNTL facilitates EGLN2 expression, thus destabilizing the prosurvival factor HIF1A, ultimately favoring lipid peroxidation and cell death. And the HIF1A inhibitor chetomin enhanced the anticancer activity of RSL3, PTGS2 mRNA expression in Lung squamous cell carcinoma. . . . Down regulation Suppressor Marker To generate murine subcutaneous tumors, 5 x 106 HT1080 cells in 100 ul of phosphate-buffered saline (PBS) were injected subcutaneously at the right of the dorsal midline in 6- to 8-week-old female athymic nude mice (no. 490, Charles River Laboratories). REF000080 ICD-11: 2C25 Lung squamous cell carcinoma CELL00143; CELL00038; CELL00095; CELL00035 Calu-1; THP1; HT1080; HL-60 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00913 The autophagy-mediated degradation of ARNTL facilitates EGLN2 expression, thus destabilizing the prosurvival factor HIF1A, ultimately favoring lipid peroxidation and cell death. And the HIF1A inhibitor chetomin enhanced the anticancer activity of RSL3, PTGS2 mRNA expression in Lung squamous cell carcinoma. . . . Up regulation Driver Marker To generate murine subcutaneous tumors, 5 x 106 HT1080 cells in 100 ul of phosphate-buffered saline (PBS) were injected subcutaneously at the right of the dorsal midline in 6- to 8-week-old female athymic nude mice (no. 490, Charles River Laboratories). REF000080 ICD-11: 2C25 Lung squamous cell carcinoma CELL00143; CELL00038; CELL00095; CELL00035 Calu-1; THP1; HT1080; HL-60 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00965 RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression. . . . Down regulation Suppressor Driver Five millions of control or RNF113A-depleted Cisplatin-resistant A549 cells were transplanted into immunodeficient NOD/SCID 8 weeks old mice. Tumors were grown up to 0.1-0.2 mm3 and mice were then treated with Cisplatin (1 mg/kg) six times every 3 days. Seven mice were used per experimental conditions. No randomization of mice was used. REF000146 ICD-11: 2C25 Lung cancer CELL00045; CELL00195; CELL00004; CELL10085 A549; H1975; 293; PCS-201-012 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01612 OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. OGFRP1 regulated cell proliferation and ferroptosis in lung cancer by inhibiting miR-299-3p to enhance SLC38A1 expression, providing a novel therapeutic strategy for lung cancer. . . . Up regulation Suppressor Driver Male nude mice (5-week-old) were purchased from Jinan Pengyue Animal Breeding Center (Jinan, China). Next, mice models were established by subcutaneously injecting A549 cells (1 x 106 cells/100 uL) into the right armpit flanks, which were stably transfected with sh-NC or sh-OGFRP1. Tumor formation was monitored and tumor volume was calculated every week for 5 weeks according to the formula: tumor volume = 1/2 (length x width2). Totally 35 days upon injection, the mice were euthanized and the tumors were dissected out from the right armpit flanks and weighted. The tumor tissues of nude mice with lung cancer were snap-frozen in liquid nitrogen immediately and stored at -80 for further research. REF000822 ICD-11: 2C25 Lung cancer CELL00045; CELL00195; CELL00076 A549; H1975; BEAS-2B Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01613 OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. OGFRP1 regulated cell proliferation and ferroptosis in lung cancer by inhibiting miR-299-3p to enhance SLC38A1 expression, providing a novel therapeutic strategy for lung cancer. . . . Down regulation Driver Driver Male nude mice (5-week-old) were purchased from Jinan Pengyue Animal Breeding Center (Jinan, China). Next, mice models were established by subcutaneously injecting A549 cells (1 x 106 cells/100 uL) into the right armpit flanks, which were stably transfected with sh-NC or sh-OGFRP1. Tumor formation was monitored and tumor volume was calculated every week for 5 weeks according to the formula: tumor volume = 1/2 (length x width2). Totally 35 days upon injection, the mice were euthanized and the tumors were dissected out from the right armpit flanks and weighted. The tumor tissues of nude mice with lung cancer were snap-frozen in liquid nitrogen immediately and stored at -80 for further research. REF000822 ICD-11: 2C25 Lung cancer CELL00045; CELL00195; CELL00076 A549; H1975; BEAS-2B Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00927 Metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc-heterodimerization partner), at both the messenger RNA and protein levels in Lung adenocarcinoma. . . . Down regulation Driver Suppressor To generate tumor xenograft models, 5 x 106 MTDH WT and KO MDA-MB-231 cells were injected into the second and fifth mammary fat pads (both sides, total four sites) of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, Jackson Laboratories, Bar Harbor, ME) immunodeficient female mice. To study the metastasis from this orthotopic mouse model, tumor volumes were allowed to grow to ~1000 mm3, after which livers were resected to examine incidence as well as tumor burden of liver metastasis. REF000093 ICD-11: 2C25 Lung adenocarcinoma CELL00045; CELL00195; CELL00362; CELL00361; CELL00181; CELL00333; CELL00123; CELL00089; CELL00024; CELL00005; CELL00002; CELL00421 A549; H1975; DMS53; DMS273; KLE; AN3CA; RL95; Hec1A; Ishikawa; MDA-MB-231; MCF-7; Hec50 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01137 The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription. . . . Down regulation Driver Suppressor For xenograft experiments, 1.5 x 107 Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation. REF000371 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00076; CELL00045; CELL00056; CELL00317; CELL00195; CELL00202; CELL00374; CELL00236; CELL00117; CELL00143 HEK 293T; BEAS-2B; A549; NCIH1299; PC-9; NCIH1975; NCIH441; NCIH1650; HCC827; NCIH292; Calu-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01161 USP35 was abundant in human lung cancer tissues and cell lines. USP35 knockdown promoted ferroptosis, and inhibited cell growth, colony formation, and tumor progression in lung cancer cells. Further studies determined that USP35 directly interacted with ferroportin (FPN) and functioned as a deubiquitinase to maintain its protein stability. . . . Up regulation Suppressor Marker/Suppressor BALB/c nude mice (4-5 weeks old) were obtained from HFK Bioscience Co., Ltd (Beijing, China) and maintained in a SPF barrier system. H460, H1299 or H1650 cell lines at a dose of 1 x 106 with or without USP35 manipulation were subcutaneously injected into the right dorsal flank of the nude mice. REF000397 ICD-11: 2C25 Lung cancer CELL00076; CELL00085; CELL00045; CELL00201; CELL00015; CELL00056; CELL00287 BEAS2B; HBE; A549; H358; H460; H1299; H1650 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01194 The miR-302a-3p mimic directly bound to the 3-UTR of FPN and decreased its protein expression, thereby causing intracellular iron overload and ferroptotic cell death, while the miR-302a-3p inhibitor significantly prevented erastin/RSL3-induced ferroptosis and tumor suppression. miR-302a-3p functions as a tumor inhibitor, via targeting ferroportin to induce ferroptosis of non-small cell lung cancer. . . . Down regulation Driver Marker/Suppressor . REF000443 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00201; CELL00056; CELL00287; CELL00076; CELL00085 A549; H358; H129; H1650; BEAS-2B; HBE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00193 The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells. Inducer . Down regulation . . Suppressor Briefly, when tumours on transplanted nude mice reached around 100 mm3, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed. REF000254 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00015; CELL00306 A549; NCI-460; SPC-A-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00226 Sulforaphane (SFN)-induced cell death was mediated via ferroptosis and inhibition of the mRNA and protein expression levels of SLC7A11 in small-cell lung cancer (SCLC) cells. The anticancer effects of SFN may provide novel options for SCLC treatment. Inducer . Down regulation . . Suppressor . REF000291 ICD-11: 2C25 Small cell lung cancer CELL00489; CELL00383; CELL00264 H69; H82; H69AR Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique00554 Capsaicin inhibited the proliferation of A549 and NCI-H23 cells and induced ferroptosis by inactivating SLC7A11/GPX4 signaling. Capsaicin could be used as a potential anticancer agent in the treatment of non-small cell lung cancer. Inducer . Down regulation . . Suppressor . REF000778 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00199 A549; NCI-H23 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00732 Manoalide (MA) induces ferroptosis by suppressing the NRF2-SLC7A11 axis and mitochondrial Ca2+overload induced-FTH1 pathways to promote the sensitivity of osimertinib-resistant lung cancer cells to osimertinib. Suppressor . Down regulation . . Suppressor The LSL-KrasG12D mouse model was obtained from the Jackson Laboratory (Sacramento, CA). Adeno-Cre (Genechem, Shanghai, China) was introduced into the trachea of mice at a dose of 1.25 x 1011 PFU in a total volume of 50 uL. Tumor tissues from 12-week post-infection mice were washed with cold PBS, cut into small pieces, and washed with DMEM/F12 (containing 1 x Glutamine, 10 mM HEPES, and antibiotics), digested with collagenase I and IV for 0.5-1 h at 37. After washing twice with DMEM/F12 and centrifugation (500 g, 5 min), the dissociated cells were seeded into growth factor-reduced matrigel (Corning, #356237) at 37 for 30 min. REF000955 ICD-11: 2C25 Lung cancer CELL00045; CELL00249; CELL00236; CELL00317 A549; H157; HCC827; PC9 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00906 The downregulation of the lncRNA MIR503HG induced by XAV939 may serve an important role in suppressing the progression of non-small cell lung cancer via sponging miR1273c, to downregulate its target SOX4. Furthermore, the downregulation of SLC7A11 induced by XAV939 may inhibit NSCLC development via participation in the ferroptosis pathway. Inducer . Down regulation . . Suppressor . REF000072 ICD-11: 2C25.Y Non-small cell lung cancer CELL00056 NCI-H1299 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01136 The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription. . . . Down regulation Driver Suppressor For xenograft experiments, 1.5 x 107 Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation. REF000371 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00076; CELL00045; CELL00056; CELL00317; CELL00195; CELL00202; CELL00374; CELL00236; CELL00117; CELL00143 HEK 293T; BEAS-2B; A549; NCIH1299; PC-9; NCIH1975; NCIH441; NCIH1650; HCC827; NCIH292; Calu-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01216 Tumors with high SOX2 expression were more resistant to ferroptosis, and SLC7A11 expression was positively correlated with SOX2 in both mouse and human lung cancer tissue. This study uncovers a SOX2-SLC7A11 regulatory axis that confers resistance to ferroptosis in lung cancer stem-like cells. . . . Up regulation Suppressor Suppressor Mice were housed in the SIBCB animal facility under SPF conditions with a 12 hours light/dark cycle at room temperature. For Erastin treatment, we sequentially dissolved Erastin in 5% DMSO, 30% PEG300, 5% Tween80 and ddH2O according to the manufacturers instructions, it should be noted that the solvent needed to be added from left to right, after the dissolution was completely clear, added the next reagent, 40 mg/kg Erastin was intraperitoneal injected, every other day for 2 weeks. For IKE treatment, 50 mg/kg IKE was intraperitoneal injected, once a day for 2 weeks. REF000476 ICD-11: 2C25 Lung cancer CELL10035; CELL00056; CELL00133; CELL00057; CELL00087 H5889; L78; H1299; SW620; HEK293T; HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01314 MiR-27a-3p, was an essential modulator of ferroptosisviadirectly targeting SLC7A11 in non-small cell lung cancer cells. Overexpressing miR-27a-3p led to SLC7A11 suppressionviadirectly binding to its 3'-UTR, followed by the reduction of erastin-caused ferroptosis. . . . Down regulation Suppressor Driver . REF000568 ICD-11: 2C25.Y Non-small cell lung cancer CELL00076; CELL00045 Beas-2B; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01357 Mechanically, circFOXP1 increased SLC7A11 expression by directly sponging miR-520a-5p in lung cancer cells. The inhibitor of miR-520a-5p or the overexpression of SLC7A11 reversed circFOXP1 shRNA-induced ferroptosis phenotypes in lung cancer cells. . . . Up regulation Suppressor Suppressor SCID/nude mice (6 weeks old) were ordered from Laboratory Animal Center of Chinese Academy of Sciences (Beijing, China). HT29 cells were co-transfected with sh-circFOXP1 and pCMV-SLC7A11 or empty vector. Cells were digested, 5 x 106 cells were mixed with Matrigel (Corning) and subcutaneously injected into mice. The width and length of tumor were measured at indicated time, and the tumor size was calculated by the formula: 0.5 x length x width2. Mice were then succumbed to death, the tumors were isolated, weighted, and made into paraffin-embedded slices (5-um). The slices were stained with anti-KI67 antibody (Santa Cruz Biotechnology) and subsequent HRP-labeled secondary antibody and captured in a microscope (Leica Microsystems). REF000618 ICD-11: 2C25 Lung cancer CELL00562 HT29 Ferroptosis (hsa04216) Cell ferroptosis
unique01358 Mechanically, circFOXP1 increased SLC7A11 expression by directly sponging miR-520a-5p in lung cancer cells. The inhibitor of miR-520a-5p or the overexpression of SLC7A11 reversed circFOXP1 shRNA-induced ferroptosis phenotypes in lung cancer cells. . . . Down regulation Driver Suppressor SCID/nude mice (6 weeks old) were ordered from Laboratory Animal Center of Chinese Academy of Sciences (Beijing, China). HT29 cells were co-transfected with sh-circFOXP1 and pCMV-SLC7A11 or empty vector. Cells were digested, 5 x 106 cells were mixed with Matrigel (Corning) and subcutaneously injected into mice. The width and length of tumor were measured at indicated time, and the tumor size was calculated by the formula: 0.5 x length x width2. Mice were then succumbed to death, the tumors were isolated, weighted, and made into paraffin-embedded slices (5-um). The slices were stained with anti-KI67 antibody (Santa Cruz Biotechnology) and subsequent HRP-labeled secondary antibody and captured in a microscope (Leica Microsystems). REF000618 ICD-11: 2C25 Lung cancer CELL00562 HT29 Ferroptosis (hsa04216) Cell ferroptosis
unique01448 SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy. . . . Up regulation Suppressor Suppressor An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 106 cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. REF000683 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01483 LncRNA Uc.339 competitively binds to pri-miR-339 and inhibits the production of mature miR-339. At the same time, it is the first to clarify the reason for the negative correlation between miR-339 and SLC7A11 expression in lung cancer, and for the first verification that the inhibition of miR-339 led to increased expression of SLC7A11 and weakens ferroptosis, which constituted an important carcinogenesis mechanism for lung adenocarcinoma metastasis. . . . Up regulation Suppressor Suppressor 6-8 weeks mice were divided into 4 groups randomly. Mice were injected with 2.5 x 105 wild type LLC cells, Uc.339 OE-LLC cells, with or without miR-339 inhibitors, respectively, through the lateral tail vain. The mice were killed after 4 weeks by carbon dioxide asphyxiation followed by cervical dislocation to ensure death. The lungs were removed, rinsed with PBS, and the number of metastatic foci on the lung surface was counted. The pulmonary lobes were subsequently kept in 4% paraformaldehyde for later paraffin embedding and hematoxylin and eosin staining. REF000712 ICD-11: 2C25.0 Lung adenocarcinoma CELL00045; CELL00056; CELL00066; CELL00317 A549; H1299; 16HBE; PC-9 Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation; Cell metastasis
unique01484 LncRNA Uc.339 competitively binds to pri-miR-339 and inhibits the production of mature miR-339. At the same time, it is the first to clarify the reason for the negative correlation between miR-339 and SLC7A11 expression in lung cancer, and for the first verification that the inhibition of miR-339 led to increased expression of SLC7A11 and weakens ferroptosis, which constituted an important carcinogenesis mechanism for lung adenocarcinoma metastasis. . . . Down regulation Driver Suppressor 6-8 weeks mice were divided into 4 groups randomly. Mice were injected with 2.5 x 105 wild type LLC cells, Uc.339 OE-LLC cells, with or without miR-339 inhibitors, respectively, through the lateral tail vain. The mice were killed after 4 weeks by carbon dioxide asphyxiation followed by cervical dislocation to ensure death. The lungs were removed, rinsed with PBS, and the number of metastatic foci on the lung surface was counted. The pulmonary lobes were subsequently kept in 4% paraformaldehyde for later paraffin embedding and hematoxylin and eosin staining. REF000712 ICD-11: 2C25.0 Lung adenocarcinoma CELL00045; CELL00056; CELL00066; CELL00317 A549; H1299; 16HBE; PC-9 Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation; Cell metastasis
unique00852 NFS1 suppression induced TFRC expression and repressed FTH1 and cytoplasmic aconitase activity. Suppression of NFS1 cooperates with inhibition of cysteine transport to trigger ferroptosis in vitro and slow tumour growth. Therefore, lung adenocarcinomas select for expression of a pathway that confers resistance to high oxygen tension and protects cells from undergoing ferroptosis in response to oxidative damage. . . . Down regulation Driver Marker/Suppressor/Driver Tumours were initiated in 4-8-week-old female NOD. CB17 Scid/J mice. Orthotopically in the mouse mammary gland, by implantation of 500,000 cells in 25 ul 33% Matrigel into the fourth mouse mammary fat pad; subcutaneously, by injection of 500,000 cells in 100 ul 33% Matrigel into the left or right flank of the mouse; via tail vein by injection of 500,000 cells in 150 ul RPMI into the mouse tail vein; and via intratracheal instillation by instilling 200,000 cells in 50 ul 2 mM EDTA as described. Cancer cells were transduced with viral shRNAs, selected for 3 days with puromycin, and allowed to recover for one day before introduction into mice. For experiments comparing subcutaneous and lung tumour formation, shRNA transduced cells were prepared at the same time and injected on the same day. Animals were imaged by IVIS (Perkin Elmer) 15 min following injection subcutaneously into the neck scruff with XenoLight d-Luciferin (165 mg per kg body weight, Perkin Elmer). Average luminescence was quantified per mouse from equal sized bins covering the mouse thorax. For experiments in which tumour growth was measured upon drug treatment, MDA-MB-231 cells, implanted as described above, were allowed to form palpable tumours (~4 mm diameter) and mice were sorted into treatment groups as described below. PEG-Cyst(e)inase was delivered via intraperitoneal injection at 50 mg per kg body weight every 3 days, SSA was delivered by daily intraperitoneal injection at 250 mg per kg body weight, and BSO was delivered in the drinking water at 20 mM with 5 mg ml-1 sucralose. REF000032 ICD-11: 2C25.0 Lung adenocarcinoma CELL00462; CELL00005; CELL00226; CELL00377; CELL00045; CELL00197; CELL00205; CELL00021; CELL00384; CELL00015; CELL00148; CELL00200; CELL00153 MCF10DCIS.com; MDA-MB-231; SW900; NCI-H196; A549; NCI-H2170; NCI-H647; 786-O; A498 NCI-H838; NCI-H460; SK-MES-1; NCI-H322 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01649 This study indicated that cinobufotalin induced ferroptosis to suppress lung cancer cell growth by lncRNA LINC00597/hsa-miR-367-3p/TFRC pathway via resibufogenin might provide novel therapeutic targets for lung cancer therapy. . . . Up regulation Driver Marker/Suppressor/Driver . REF000857 ICD-11: 2C25 Lung cancer CELL00045; CELL00148; CELL00057 A549; SK-MES-1; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01650 This study indicated that cinobufotalin induced ferroptosis to suppress lung cancer cell growth by lncRNA LINC00597/hsa-miR-367-3p/TFRC pathway via resibufogenin might provide novel therapeutic targets for lung cancer therapy. . . . Down regulation Suppressor Marker/Suppressor/Driver . REF000857 ICD-11: 2C25 Lung cancer CELL00045; CELL00148; CELL00057 A549; SK-MES-1; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00840 LSH (HELLS) is involved in ferroptosis and is a potential therapeutic target in cancer because of its crucial role in ferroptosis. LSH functioned as an oncogene in lung cancer in vitro and in vivo. And LSH promotes the lipid metabolic genes, including SCD1 and FADS2. . . . Up regulation Suppressor Suppressor SCID Mice (Hunan SJA Laboratory Animal Co.Ltd.) were injected with A549 (1 x 106 cells/mouse) or H358 (2 x 106 cells/mouse) cells via mammary fat pad (10 mice/group). Mice with A549 or H358 cells were imaged from dorsal and ventral views every three days. REF000024 ICD-11: 2C25 Lung cancer CELL00342; CELL00085; CELL00045; CELL00201; CELL00204; CELL00317; CELL00486; CELL00309; CELL00057 MRC-5; HBE; A549; H358; H522; PC9; 95C; 95D; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01134 METTL3 was confirmed as a direct target gene of miR-4443. Further mechanistic analysis showed that miR-4443 regulated the expression of FSP1 in an m6A manner via METLL3. A high level of exosomal miR-4443 conferred cisplatin resistance in non-small cell lung carcinoma (NSCLC) via METTL3/FSP1-mediated ferroptosis. . . . Up regulation Suppressor Suppressor BALB/c nude mice (male, 4 weeks old) were purchased from the Animal Center of Nanjing University with free access to water and food. A549 cells (106 cells per mouse) transfected with miR-4443 mimic or mimic-NC were injected subcutaneously to generate subcutaneous tumors. Tumor volume was recorded. REF000370 ICD-11: 2C25.Y Non-small cell lung cancer CELL00057; CELL00066; CELL00281; CELL00015; CELL00045; CELL00056 HEK293T; 16HBE; PGCL3; H460;H1299; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01135 METTL3 was confirmed as a direct target gene of miR-4443. Further mechanistic analysis showed that miR-4443 regulated the expression of FSP1 in an m6A manner via METLL3. A high level of exosomal miR-4443 conferred cisplatin resistance in non-small cell lung carcinoma (NSCLC) via METTL3/FSP1-mediated ferroptosis. . . . Down regulation Driver Suppressor BALB/c nude mice (male, 4 weeks old) were purchased from the Animal Center of Nanjing University with free access to water and food. A549 cells (106 cells per mouse) transfected with miR-4443 mimic or mimic-NC were injected subcutaneously to generate subcutaneous tumors. Tumor volume was recorded. REF000370 ICD-11: 2C25.Y Non-small cell lung cancer CELL00057; CELL00066; CELL00281; CELL00015; CELL00045; CELL00056 HEK293T; 16HBE; PGCL3; H460;H1299; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00280 11-hydroxy-ent-16-kaurene-15-one possessed strong inhibitory activity against several cancer cell lines. Moreover, compound 23 induced both apoptosis and ferroptosis through increasing cellular ROS levels in HepG2 cells. ROS accumulation induced by compound 23 was caused by inhibition of antioxidant systems through targeting peroxiredoxin I (Prdx I) and depletion of GSH in lung adenocarcinoma cells. Inducer Down regulation . . Suppressor . Thirty male athymic (Balb/c-nu) mice (4-week-old) were purchased from the SPF (Beijing) biotechnology (Beijing, China) and allowed to acclimatize for 1 week. A549/CDDP cells (5 x 106 cells) were injected subcutaneously into the right anterior flanks of the mice. Two weeks after the injection of cells, when the tumors became palpable (around 100 mm3), mice were randomly divided into four groups (n = 6 per group). Tumor-bearing mice were received equal amount of solvent, CDDP (4 mg/kg) or compound 23 (10 mg/kg) or combination CDDP and 23 were injected via intraperitoneal injection. Administration was performed every 3 days for 30 days. REF000392 ICD-11: 2C25 Lung adenocarcinoma CELL00045; CELL00048; CELL00021; CELL00085; CELL00304; CELL10037 A549; HepG2; 7860; A2870; HBE; HL-7702; HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00281 11-hydroxy-ent-16-kaurene-15-one possessed strong inhibitory activity against several cancer cell lines. Moreover, compound 23 induced both apoptosis and ferroptosis through increasing cellular ROS levels in HepG2 cells. ROS accumulation induced by compound 23 was caused by inhibition of antioxidant systems through targeting peroxiredoxin II (Prdx II) and depletion of GSH in lung adenocarcinoma cells. Inducer Down regulation . . Suppressor . Thirty male athymic (Balb/c-nu) mice (4-week-old) were purchased from the SPF (Beijing) biotechnology (Beijing, China) and allowed to acclimatize for 1 week. A549/CDDP cells (5 x 106 cells) were injected subcutaneously into the right anterior flanks of the mice. Two weeks after the injection of cells, when the tumors became palpable (around 100 mm3), mice were randomly divided into four groups (n = 6 per group). Tumor-bearing mice were received equal amount of solvent, CDDP (4 mg/kg) or compound 23 (10 mg/kg) or combination CDDP and 23 were injected via intraperitoneal injection. Administration was performed every 3 days for 30 days. REF000392 ICD-11: 2C25 Lung adenocarcinoma CELL00045; CELL00048; CELL00021; CELL00085; CELL00304; CELL10037 A549; HepG2; 7860; A2870; HBE; HL-7702; HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00055 Combined treatment with oxyfedrine (OXY) and sulfasalazine (SSZ) was found to induce accumulation of the cytotoxic aldehyde 4-hydroxynonenal and cell death in SSZ-resistant cancer cells both in vitro and in vivo. And the constitutive activation of Nrf2 results in high expression of xCT and ALDH3A1, and Nrf2 depletion sensitizes Nrf2 overexpressing cancer, such as lung small cell carcinoma, cells to combination therapy with OXY and SSZ. Inducer Down regulation . . Suppressor . . REF000105 ICD-11: 2C25 Lung small cell carcinoma CELL00538; CELL00087; CELL00391; CELL00176; CELL00177; CELL00178; CELL00428; CELL00218; CELL00045 DMS114; HCT116; SBC3; HSC2; HSC3; HSC4; OSC19; SCC25; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00241 The PARK7 gene (encode DJ-1 protein) was first discovered as an oncogene and later found to be a causative gene for autosomal recessive early onset Parkinson's disease. 1,1-(Decane-1,10-diyl)bis(5-fluoroindoline-2,3-dione) (DM10) is identified as a potent inhibitor targeting DJ-1 homodimer with the potential as sensitizing agent for other anticancer drugs. Inducer Down regulation . . Suppressor . Tumors were established by injecting 200 uL of H1299 cell suspensions (2 x 106) into BALB/c female athymic nude mice (5 weeks, National Rodent Laboratory Animal Resource, Shanghai, China). When the tumor volume reached an average size of 80 mm3, tumor-bearing mice were subsequently randomly divided into three groups (n = 7 for each group). STK or DM10 was intratumorally administered as a single agent in mouse tumors at a dose of 30 or 15 mg/kg only once. REF000308 ICD-11: 2C25 Lung large cell carcinoma CELL00056; CELL00317; CELL00005; CELL00086; CELL00291; CELL00048; CELL00021; CELL00121; CELL00057 H1299; PC9; MDA-MB-231; HCC1937; BEL7402; HepG2; 786-O; RCC4; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01667 Realgar-induced ferroptosis may be mediated via KRAS/Raf/MAPK. Realgar may be targeted to regulate Raf kinase, thereby further regulating the downstream JNK/ERK signaling cascade to suppress KRAS cells and exert an anticancer activity. In conclusion, realgar may induce ferroptosis by regulating the Raf, and hence plays a role in antiKRAS mutant lung cancer. Inducer Up regulation . . Driver . . REF000876 ICD-11: 2C25 Lung cancer CELL00199; CELL00045; CELL00015; CELL00287 H23; A549; H460; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01770 Tectoridin synergized with PLK1 inhibitor to suppress autophagy and ferroptosis but promoted caspase-3-mediated apoptosis in A549 (Lung adenocarcinoma) cells. Our findings highlight a potential drug target and the combination therapy strategy of PLK1 inhibitor and tectoridin for LUAD patients. In vitro experiments, we confirmed that tectoridin could inhibit the expression of PLK1. Suppressor Down regulation . . Driver . . REF001000 ICD-11: 2C25.0 Lung adenocarcinoma CELL00045 A549 Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00582 d-borneol in combination with cisplatin induced ferroptosisviaNCOA4-mediated ferritinophagy and also increased the expression levels of ACSL4, regulated PCBP2 and PRNP to promote the conversion of Fe3+to Fe2+, reduced the activity or expression of antioxidants enzymes (GSH and HO-1), and induced ROS accumulation and thereby promoted ferroptosis. In addition, activation of autophagy inhibited progression of the EMT and increased sensitivity to cisplatin in cisplatin-resistant lung cancer cells. Inducer Down regulation . . Suppressor . Male Balb/c nude mice (4-week-old) were purchased from SPF (Beijing) biotechnology co., LTD and maintained in the Experimental Animal Research Center of Chengdu University of TCM. After 1 week of adaptable feeding, H460/CDDP cells (5 x 106 cells in 0.1 ml phosphate-buffered saline) were subcutaneously injected into the right dorsal flank to establish tumor model. When the tumor volume grows to 100 mm3, the tumor-bearing mice were randomly divided into the following four treatment groups: a control group (Con, n = 6): intraperitoneal injection of saline once a day; vehicle group (Vehicle, n = 6): intragastric administration of 2% tween and intraperitoneal injection of saline; d-borneol low-dose group (Bor-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day; d-borneol high-dose group (Bor-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day; CDDP group (CDDP, n = 6): intraperitoneal injection of cisplatin (3 mg/kg) every two days; a low-dose combination treatment group (C+B-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days; a high-dose combination treatment group (C+B-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days. We usually first orally gavage d-borneol, and then inject cisplatin intraperitoneally half an hour later. After 14 days treatment, the samples were obtained from the mice for the further experiments. REF000809 ICD-11: 2C25.Y Non-small cell lung cancer CELL00507 H460/CDDP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell autophagy
unique00905 The downregulation of the lncRNA MIR503HG induced by XAV939 may serve an important role in suppressing the progression of non-small cell lung cancer via sponging miR1273c, to downregulate its target SOX4. Furthermore, the downregulation of SLC7A11 induced by XAV939 may inhibit NSCLC development via participation in the ferroptosis pathway. Inducer Down regulation . . Suppressor . . REF000072 ICD-11: 2C25.Y Non-small cell lung cancer CELL00056 NCI-H1299 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00218 6-Gingerol inhibits lung cancer cell growth via suppression of USP14 expression and its downstream regulation of autophagy-dependent ferroptosis, revealing the function and efficacy of 6-Gingerol as a therapeutic compound in A549 and its possible mechanism of action. Inducer Down regulation . . Suppressor . BALB/cNude (6-8 weeks of age) mice were purchased from Hangzhou Ziyuan Experimental Animal Technology Co. Ltd. (SYXK-20180049) for this study. The mice were housed under specific pathogen-free conditions at 23 and given free access to food and water. The left flank of mice was subcutaneously inoculated with A549 tumor-cell suspension (5 x 106 cells/100uL) to prepare A549 tumor xenografts. Three days after tumor cell inoculation, the mice were divided into three groups (n = 8): Con group (control group, no treatment), L-Gin group (0.25 mg/kg/day 6-Gingerol), H-Gin group (0.5 mg/kg/day 6-Gingerol), which were administered orally daily until the end of the experiments. Mice were killed when their minor axis of tumors were longer than 20 mm. REF000278 ICD-11: 2C25 Lung cancer CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00581 d-borneol in combination with cisplatin induced ferroptosisvia NCOA4-mediated ferritinophagy and also increased the expression levels of ACSL4, regulated PCBP2 and PRNP to promote the conversion of Fe3+ to Fe2+, reduced the activity or expression of antioxidants enzymes (GSH and HO-1), and induced ROS accumulation and thereby promoted ferroptosis. In addition, activation of autophagy inhibited progression of the EMT and increased sensitivity to cisplatin in cisplatin-resistant lung cancer cells. Inducer Up regulation . . Driver . Male Balb/c nude mice (4-week-old) were purchased from SPF (Beijing) biotechnology co., LTD and maintained in the Experimental Animal Research Center of Chengdu University of TCM. After 1 week of adaptable feeding, H460/CDDP cells (5 x 106 cells in 0.1 ml phosphate-buffered saline) were subcutaneously injected into the right dorsal flank to establish tumor model. When the tumor volume grows to 100 mm3, the tumor-bearing mice were randomly divided into the following four treatment groups: a control group (Con, n = 6): intraperitoneal injection of saline once a day; vehicle group (Vehicle, n = 6): intragastric administration of 2% tween and intraperitoneal injection of saline; d-borneol low-dose group (Bor-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day; d-borneol high-dose group (Bor-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day; CDDP group (CDDP, n = 6): intraperitoneal injection of cisplatin (3 mg/kg) every two days; a low-dose combination treatment group (C+B-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days; a high-dose combination treatment group (C+B-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days. We usually first orally gavage d-borneol, and then inject cisplatin intraperitoneally half an hour later. After 14 days treatment, the samples were obtained from the mice for the further experiments. REF000809 ICD-11: 2C25.Y Non-small cell lung cancer CELL00507 H460/CDDP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell autophagy
unique00319 Levobupivacaine could inhibit the proliferation and induce the apoptosis of non-small cell lung cancer (NSCLC) cells. Levobupivacaine was able to attenuate the invasion and migration in the cells. The treatment of levobupivacaine remarkably increased the levels of ROS, iron, and Fe2+ in NSCLC cells. Mechanically, levobupivacaine up-regulated the expression of p53 and induced ferroptosis by regulating p53 in NSCLC cells. Inducer Up regulation . . Driver . Balb/c nude mice (n= 5, 4-week-old, male) were applied to detect the impact of levobupivacaine on tumor growth. Mice subcutaneously injected with 1 x 107 A549 cells were treated with levobupivacaine (40 umol/Kg) or equal volume saline. The tumor volume was remarked every 5 days and finished at 30 days after injection, followed by the analysis of volume (length (width/2)2) and weight. REF000441 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00355 A549; A427 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique00904 The downregulation of the lncRNA MIR503HG induced by XAV939 may serve an important role in suppressing the progression of non-small cell lung cancer via sponging miR1273c, to downregulate its target SOX4. Furthermore, the downregulation of SLC7A11 induced by XAV939 may inhibit NSCLC development via participation in the ferroptosis pathway. Inducer Up regulation . . Driver . . REF000072 ICD-11: 2C25.Y Non-small cell lung cancer CELL00056 NCI-H1299 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00903 The downregulation of the lncRNA MIR503HG induced by XAV939 may serve an important role in suppressing the progression of non-small cell lung cancer via sponging miR1273c, to downregulate its target SOX4. Furthermore, the downregulation of SLC7A11 induced by XAV939 may inhibit NSCLC development via participation in the ferroptosis pathway. Inducer Down regulation . . Suppressor . . REF000072 ICD-11: 2C25.Y Non-small cell lung cancer CELL00056 NCI-H1299 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00918 CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL in Pleural mesothelioma. . . . Up regulation Suppressor Marker/Suppressor . REF000083 ICD-11: 2C26 Pleural mesothelioma CELL00455; CELL00500; CELL00378; CELL00436 ACC-Meso-1; NCIH2373; NCIH2052; MeT-5A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration
unique00104 ML210 is a prodrug that is converted in cells into a nitrile-oxide electrophile that covalently inhibits GPX4 with remarkable proteome-wide selectivity in melanoma. Inducer . Down regulation . . Suppressor . REF000157 ICD-11: 2C30 Melanoma CELL00189; CELL00055; CELL00516; CELL00533; CELL00477; CELL00365; CELL00172; CELL00095; CELL00153; CELL00340; CELL00025; CELL00318 LOX-IMVI; U2OS; HEK2936E; CJM; WM88; KP4; HCC4006; HT1080; A498; CAKI2; PANC02; MC38 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00499 Sesquiterpene lactones DET and DETD-35 significantly reprogram this metabolic adaptation and inhibit GPX4 activity to disturb glutathione metabolism and induce ferroptosis. Targeting ferroptosis and GPX4 could be a novel approach to cope with drug resistance in melanoma cancers. Inducer . Down regulation . . Suppressor . REF000672 ICD-11: 2C30 Melanoma CELL00053; CELL00531; CELL00069; CELL00154; CELL00060 HaCaT; CCD966SK; A375; A2058; SK-MEL-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation
unique00500 Sesquiterpene lactones DET and DETD-35 significantly reprogram this metabolic adaptation and inhibit GPX4 activity to disturb glutathione metabolism and induce ferroptosis. Targeting ferroptosis and GPX4 could be a novel approach to cope with drug resistance in melanoma cancers. Inducer . Down regulation . . Suppressor . REF000672 ICD-11: 2C30 Melanoma CELL00053; CELL00531; CELL00069; CELL00154; CELL00060 HaCaT; CCD966SK; A375; A2058; SK-MEL-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation
unique01187 MiR-130b-3p is able to inhibit the ferroptosis induced by erastin or RSL3 in melanoma cells by targeting DKK1 and subsequent activation of Nrf2/HO-1 pathway. . . . Up regulation Suppressor Marker/Suppressor NU/NU nude mice were purchased from Hunan Slac Laboratory Animals Co., Ltd. (Changsha, China). Melanoma cells (5 x 106) were injected subcutaneously into the left posterior side of 7-week-old immunodeficient female mice. The tumor growth was monitored by measuring the length (L) and width (W) of the tumor. Tumor volume = 1/2 (length x width2). When the tumor volume reached about 50 mm3, mice were randomly assigned into 8 groups (n = 6) and given intraperitoneal injection of erastin for 20 days. Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma) in the test tube heated at 37 and gently shaken before use. REF000430 ICD-11: 2C30 Melanoma CELL00328; CELL00069; CELL00163; CELL00294; CELL00179; CELL00115; CELL00470; CELL00472; CELL00591 PIG1; A375; G-361; HS1-CLS; MEL-CLS1-4; IGR-1; MEWO; NIS-G; WS1-CLS; MML1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01188 MiR-130b-3p is able to inhibit the ferroptosis induced by erastin or RSL3 in melanoma cells by targeting DKK1 and subsequent activation of Nrf2/HO-1 pathway. . . . Down regulation Driver Marker/Suppressor NU/NU nude mice were purchased from Hunan Slac Laboratory Animals Co., Ltd. (Changsha, China). Melanoma cells (5 x 106) were injected subcutaneously into the left posterior side of 7-week-old immunodeficient female mice. The tumor growth was monitored by measuring the length (L) and width (W) of the tumor. Tumor volume = 1/2 (length x width2). When the tumor volume reached about 50 mm3, mice were randomly assigned into 8 groups (n = 6) and given intraperitoneal injection of erastin for 20 days. Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma) in the test tube heated at 37 and gently shaken before use. REF000430 ICD-11: 2C30 Melanoma CELL00328; CELL00069; CELL00163; CELL00294; CELL00179; CELL00115; CELL00470; CELL00472; CELL00591 PIG1; A375; G-361; HS1-CLS; MEL-CLS1-4; IGR-1; MEWO; NIS-G; WS1-CLS; MML1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01051 The lipogenesis regulator SREBP2 directly induces transcription of the iron carrier Transferrin (TF), reducing intracellular iron pools, reactive oxygen species, and lipid peroxidation, thereby conferring resistance to inducers of ferroptosis. SREBP2-driven iron homeostatic pathways contribute to cancer progression, drug resistance, and metastasis in melanoma cancers. . . . Up regulation Suppressor Marker/Suppressor/Driver For primary tumorigenesis assays, NOD-scid Il2rg-/-mice (6-8 weeks old, female) were injected subcutaneously in the left flank with cultured CTCs, and tumors were harvested when they reached 2 centimeters in diameter. REF000266 ICD-11: 2C30 Melanoma CELL10053; CELL00237; CELL00609; CELL00164; CELL00069 CTCs; IGR-37; SKML28; GAK; A375 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique00955 Knockdown of Nedd4 leads to elevated protein level of VDAC2/3, which increased the sensitivity of melanoma cells to erastin both in vitro and in vivo. . . . Down regulation Suppressor Driver/Suppressor NU/NU Nude mice were purchased from Charles River (Beijing). To generate murine subcutaneous tumors, melanoma cells (5 x 106 cells per mouse) were injected subcutaneously into the left posterior flanks of 7-week-old immunodeficient female nude mice. REF000127 ICD-11: 2C30 Melanoma CELL00069; CELL00163; CELL00115; CELL00060; CELL00347; CELL00142; CELL00352; CELL00057 A375; G-361; MeWo; SK-MEL-2; SK-MEL-3; SK-MEL-24; WM2032; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00956 Knockdown of Nedd4 leads to elevated protein level of VDAC2/3, which increased the sensitivity of melanoma cells to erastin both in vitro and in vivo. . . . Down regulation Suppressor Driver/Suppressor NU/NU Nude mice were purchased from Charles River (Beijing). To generate murine subcutaneous tumors, melanoma cells (5 x 106 cells per mouse) were injected subcutaneously into the left posterior flanks of 7-week-old immunodeficient female nude mice. REF000127 ICD-11: 2C30 Melanoma CELL00069; CELL00163; CELL00115; CELL00060; CELL00347; CELL00142; CELL00352; CELL00057 A375; G-361; MeWo; SK-MEL-2; SK-MEL-3; SK-MEL-24; WM2032; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00753 Lorlatinib sensitized melanoma to ferroptosis through targeting IGF1R-mediated PI3K/AKT/mTOR signaling axis and its downstream SCD expression. Inducer . Down regulation . . Suppressor All animal experiments were approved by the Ethical Review of Experimental Animals at Central South University. To generate subcutaneous tumors, 2 x 106 control A375 cells or GPX4 KO cells were suspended in 100 ul PBS and injected subcutaneously into nude mice (Shanghai SLAC). Tumor-bearing mice were randomly allocated into groups and treated with vehicle (2% DMSO + 30% PEG300, per day by orally) or lorlatinib (10 mg/kg, per day by orally). Liproxstatin-1 (10 mg/kg) was administrated through intraperitoneal injection per day. Tumors were weighted and photographed on day 18 after treatment. Tumor size were recorded every three days and calculated as [(length x width x width)/2]. REF000977 ICD-11: 2C30 Melanoma CELL00609; CELL00069; CELL00348; CELL00126; CELL00021; CELL00081; CELL00005; CELL00057 SK-MEL-28; A375; WM35; SK-MEL-5; 786-O; Caki-1; MDA-231; HEK293T Fatty acid metabolism (hsa01212); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique00752 Lorlatinib sensitized melanoma to ferroptosis through targeting IGF1R-mediated PI3K/AKT/mTOR signaling axis and its downstream SCD expression. Inducer Down regulation . . Suppressor . All animal experiments were approved by the Ethical Review of Experimental Animals at Central South University. To generate subcutaneous tumors, 2 x 106 control A375 cells or GPX4 KO cells were suspended in 100 ul PBS and injected subcutaneously into nude mice (Shanghai SLAC). Tumor-bearing mice were randomly allocated into groups and treated with vehicle (2% DMSO + 30% PEG300, per day by orally) or lorlatinib (10 mg/kg, per day by orally). Liproxstatin-1 (10 mg/kg) was administrated through intraperitoneal injection per day. Tumors were weighted and photographed on day 18 after treatment. Tumor size were recorded every three days and calculated as [(length x width x width)/2]. REF000977 ICD-11: 2C30 Melanoma CELL00609; CELL00069; CELL00348; CELL00126; CELL00021; CELL00081; CELL00005; CELL00057 SK-MEL-28; A375; WM35; SK-MEL-5; 786-O; Caki-1; MDA-231; HEK293T Fatty acid metabolism (hsa01212); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique00274 a-eleostearic acid (ESA)-triggered ferroptosis is mediated by acyl-CoA synthetase long-chain isoform 1 (ACSL1), which promotes ESA incorporation into neutral lipids including triacylglycerols in Breast adenocarcinoma. Inducer . Up regulation . . Driver Mice were housed in a dedicated laboratory animal facility with 12-h light:dark cycle, at 70F+/-2 degrees, and 40-70% relative humidity. Orthotopic xenografts were generated by implanting 2.5 million MDA-MB-231 cells in 100 uL phosphate-buffered saline (PBS) mixed with 100 uL growth factor-reduced Matrigel (Corning) bilaterally into the fourth inguinal fat pad of four- to six-week-old female NOD. REF000381 ICD-11: 2C60 Breast adenocarcinoma CELL00112; CELL00005; CELL00077; CELL00156; CELL00171; CELL00169; CELL00166; CELL00165; CELL00173; CELL00010; CELL00141; CELL00270 MDA-MB-468; MDA-MB-231; BT-20; BT-549; HCC38; HCC1806; HCC1187; HCC1143; HCC70; Hs-578T; MCF-10A; MCF-12A; Lenti-X 293T; TNBC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00911 In epithelial cells, such interactions mediated by E-cadherin suppress ferroptosis by activating the intracellular NF2 (also known as merlin) and Hippo signalling pathway in breast adenocarcinoma. Antagonizing this signalling axis allows the proto-oncogenic transcriptional co-activator YAP to promote ferroptosis by upregulating several ferroptosis modulators, including ACSL4 and TFRC. . . . Up regulation Driver Driver Six- to eight-week-old female athymic nu/nu mice were purchased from Envigo (East Millstone, NJ, USA). For s.c. tumour models, mice were injected in the right flank with 1 x 107 shNT-GPX4 iKO MSTO-211H cells or shMerlin-GPX4 iKO MSTO-211H cells suspended in 150 uL Matrigel. Tumours were measured with callipers every 3 days. When tumours reached a mean volume of 100 mm3, mice with similarly sized tumours were grouped into four treatment groups. For control or knockout cohorts, mice were given intraperitoneal (i.p.) injections of 0.9% sterile saline or Doxycycline (100 mg/kg body weight) for two days. At the same time, mice were provided with either a normal diet or Doxycycline diet for control or knockout cohorts, respectively. REF000079 ICD-11: 2C60 Breast adenocarcinoma CELL10119; CELL10113; CELL00005; CELL00078; CELL00287 MEFs; NF639; MDA-MB-231; BT474; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique00297 Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis. Inducer . Up regulation . . Driver MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 106 cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day. REF000417 ICD-11: 2C60 Triple-negative breast cancer CELL00005; CELL00010; CELL00002; CELL00135; CELL00277; CELL00156; CELL00111 MDA-MB-231; HS578T; MCF-7; T47D; HBL-100; BT549; MDA-MB-453; NHFB Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01266 The present study demonstrated that miR-5096 targets and downregulates SLC7A11, thereby providing a mechanistic basis for ferroptosis in human breast cancer cells. In addition, miR-5096 induced cell death via ferroptosis, characterized by mitochondrial shrinkage with partial loss of cristae with simultaneous changes in ACSL4, ROS, lipid ROS, OH-, reactive iron, GSH, and MMP levels. . . . Up regulation Driver Driver Mating was setup 2 days prior to injection day and zebrafish embryos were collected and incubated in E3 embryo medium (5 mM NaCl, 0.17 mM KCl, 10 mM HEPES, 0.33 mM MgSO4·7H2O, 0.33 mM CaCl2·6H2O, and 0.00001% methylene blue) containing 0.2 mM N-phenyl-thiourea (PTU) (catalog no: P7629, Sigma-Aldrich). Two days post-fertilization, the chorion was removed manually using fine forceps, and the embryos were anesthetized using E3 medium containing 200 mg/L Ethyl 3-aminobenzoate methanesulfonate (Tricaine) (catalog no: A5040, Sigma-Aldrich). Anesthetized embryos were mounted in 0.7% low melting agarose containing 200 ug/ml of Tricaine and were microinjected with 500 cells in the yolk sac using Nanoject III (catalog no: 3-000-207; Drummond Scientific Company, PA, USA). At 1 day post-injection (dpi), embryos with similar graft size were selected and imaged using both bright field and RFP channels and incubated in E3-PTU medium containing 5 ug/ml doxycycline at 34 until further imaging. At 4 dpi, embryos were anesthetized and imaged again using both bright field and RFP channels using Olympus IX-73 microscope. Cells that migrated outside the yolk sac (injection site) were represented by a notable fluorescent dot and considered a metastatic event; these were counted manually for all embryos in each experimental group. REF000513 ICD-11: 2C60-2C65 Breast cancer CELL00112; CELL00111; CELL00156; CELL00005; CELL00003; CELL00135; CELL00002; CELL00019; CELL00141 MDA-MB-468; MDA-MB-453; BT-549; MDAMB-231; SKBR-3; T-47D; MCF-7; ZR-75; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01869 Molecular docking study indicated that robustaflavone 7,5'-dimethyl ether (8) is a potential strong inhibitor, which induce ferroptosis via down-regulating the expression level of ACSL4 proteins in human breast cancer MCF-7 cells. Inducer . Down regulation . . Driver . REF000603 ICD-11: 2C60-2C65 Breast cancer CELL00002 MCF-7 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00521 Lycium barbarum polysaccharide (LBP) effectively inhibited proliferation of breast cancer cells and promoted ferroptosis by modulation of the xCT/GPX4 pathway. GPX4 inactivity and repression of SLC7A11 (the gene for xCT) result in ROS accumulation, thereby modulating ferroptosis. Inducer . Down regulation . . Suppressor . REF000715 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00005 MCF-7; MDA-MB-231 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00679 The combined treatment of etoposide and erastin synergistically induced oxidative stress and lipid peroxidation, while suppressing glutathione peroxidase activity in breast cancer cells. More importantly, the combination treatment synergistically increased iron accumulation, which was associated with altered expression of IREB2/FPN1. Additionally, ferroptosis-regulating proteins ACSF2 and GPX4 were altered more potently by the combination treatment, compared to untreated cells and erastin treatment alone (p<0.05). Inducer . Down regulation . . Suppressor . REF000902 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00141; CELL00005 MCF-7; MCF-10A; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00776 Tubastatin A (Tub) as a novel GPX4 inhibitor that induced ferroptosis through large-scale drug screening. We showed that IR-mediated GPX4 expression restrained ferroptosis to drive radioresistance in breast cancer. Inducer . Down regulation . . Suppressor Female 5-week-old athymic nude mice were obtained from Sun Yat-sen University. All mice were kept under specific-pathogen free conditions in the animal facility of Sun Yat-sen University Cancer Centre. Cancer cells were suspended and counted in 1 x DMEM, and 2 x 106 MDA-MB-231 cells were injected into mice subcutaneously. When the tumours reached 50-100 mm3, the mice were randomly assigned to different treatment groups. Tumours were irradiated with a JL Shepherd Mark I-68A irradiator at a dose of 10 Gy. Tub was dissolved in solvent containing 1% DMSO, 30% polyethylene glycol, 1% Tween 80 and 68% H2O and then subcutaneously administered to mice at a dose of 2.5 mg/kg once a day. Lipro-1 diluted in PBS was intraperitoneally injected daily at a dose of 10 mg/kg. Tub or Lipro-1 was administered three times before irradiation followed by continued daily administration until the endpoint, as indicated in the corresponding figures. REF000996 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00002 MDA-MB-231; MCF-7 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01577 TMEM189 (PEDS1) could inhibit autophagy to mediate ferroptosis in breast cancer cells. Moreover, TMEM189 ablation strongly up-regulated LC3BII and transferrin receptor 1 (TfR1) expression levels in breast cancer cells, whereas down-regulated p62 and GPX4. . . . Up regulation Suppressor Suppressor Twenty BALB/c nude female mice (4- to 6-week-old) were purchased from Charles River Laboratories (Beijing, China) to establish tumorigenesis (5 mice in each). We injected MCF-7 or MDA-MB-231 cells (4 x 106) transfected with the stable knockdown and over-expressing TMEM189 into the flanks of mice to construct tumorigenesis models, respectively. Meanwhile, the sh-Con and empty vector were served as the control groups for each model. REF000783 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00005 MCF-7; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique01773 RUNX1-IT1 promotes breast cancer carcinogenesis through blocking ferroptosis via elevating GPX4, targeting of the previously unappreciated regulatory axis of RUNX1-IT1/IGF2BP1/GPX4 may be a promising treatment for patient with breast cancer. . . . Up regulation Suppressor Suppressor MDA-MB-231 cells with stable RUNX1-IT1 knockdown were injected into NOD/SCID mice, which were randomly divided into three groups, five in each group. The protocol of establishment of breast cancer orthotopic transplantation model was described in our previous study. REF001004 ICD-11: 2C60-2C65 Breast cancer CELL00135; CELL00005 T47D; MDA-MB-231 Ferroptosis (hsa04216) Cell ferroptosis
unique01774 RUNX1-IT1 promotes breast cancer carcinogenesis through blocking ferroptosis via elevating GPX4, targeting of the previously unappreciated regulatory axis of RUNX1-IT1/IGF2BP1/GPX4 may be a promising treatment for patient with breast cancer. . . . Up regulation Suppressor Suppressor MDA-MB-231 cells with stable RUNX1-IT1 knockdown were injected into NOD/SCID mice, which were randomly divided into three groups, five in each group. The protocol of establishment of breast cancer orthotopic transplantation model was described in our previous study. REF001004 ICD-11: 2C60-2C65 Breast cancer CELL00135; CELL00005 T47D; MDA-MB-231 Ferroptosis (hsa04216) Cell ferroptosis
unique00272 Shuganning injection (SGNI) induced a ferroptotic cell death of Triple-negative breast cancer (TNBC) cells. Mechanistically, SGNI induced ferroptosis was dependent on HO-1, which promotes intracellular labile iron pool accumulation, and was alleviated by HO-1 knockdown and inhibition by tin protoporphyrin IX. Inducer . Up regulation . . Driver/Suppressor MDA-MB-231 cells resuspended in PBS (2 x 106/100 m1) were injected subcutaneously into bothhind limbsof 4-6 weeks old femalenude mice. A week later, SGNI was administrated byintraperitoneal injectionat a dose of 112.5 mg/kg/3 d. REF000377 ICD-11: 2C60 Triple-negative breast cancer CELL00003; CELL00005; CELL00112; CELL00156; CELL00141; CELL00021; CELL00070; CELL00087; CELL00048; CELL00045; CELL00304; CELL00274; CELL00044; CELL00095 SK-BR-3; MDA-MB-231; MDA-MB-468; BT-549; MCF10A; 786-O; A2780; HCT116; HepG2; A549; Lo2; WPMY-1; U-87 MG; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00676 The combined treatment of etoposide and erastin synergistically induced oxidative stress and lipid peroxidation, while suppressing glutathione peroxidase activity in breast cancer cells. More importantly, the combination treatment synergistically increased iron accumulation, which was associated with altered expression of IREB2/FPN1. Additionally, ferroptosis-regulating proteins ACSF2 and GPX4 were altered more potently by the combination treatment, compared to untreated cells and erastin treatment alone (p<0.05). Inducer . Up regulation . . Driver . REF000902 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00141; CELL00005 MCF-7; MCF-10A; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01028 ATF2 inhibited BETi-induced ferroptosis by increasing NRF2 expression. Altogether, ATF2 suppressed ani-tumor effects of BETi in a negative feedback manner by attenuating ferroptosis. BETi combined with ATF2 or NRF2 inhibitor might be a novel strategy for treatment of Breast cancer. . . . Up regulation Suppressor Marker/Suppressor Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). Mice was randomly divided into different groups (n = 6 per group), 1 x 106 MB-231 cells with stable overexpression of ATF2 and control cells were subcutaneously inoculated on the right flanks. Seven days later, mice were injected intraperitoneally with PBS containingdimethyl sulfoxide(DMSO) and JQ1 (50 mg/kg) once every 2-4 days for 8 times, and the tumor volumes and body weight of mice were monitored and recorded every 23 days. REF000243 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00156; CELL00049; CELL00045 MDA-MB-231; BT-549; HeLa; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01804 Loss of PTEN activates AKT kinase to inhibit GSK3, increasing NF-E2 p45-related factor 2 (NRF2) along with transcription of one of its known target genes encoding xCT in breast cancers. . . . Down regulation Driver Marker/Suppressor A cross between 12 week old, B6.129S4 Ptenfl/fl mice obtained from Jackson Laboratory was set up and 14 days later both male and female embryos were harvested from the pregnant females. Highly vascularized sections of the embryos were removed - head, extremities, and liver. The remainder was minced via a scalpel and resuspended in 0.25% trypsin using a pipet. The cells were then incubated for 10 min in an incubator at 37 with 5% CO2 before being further resuspended into single cell suspension. The cells were then spun down at 1500 RPM for 5 min to remove the trypsin, after which they were resuspended in 10 mL of fresh media and transferred to a 10 cm dish. REF001034 ICD-11: 2C60 Breast ductal carcinoma CELL00168; CELL00167; CELL00198; CELL00203; CELL00019; CELL00086; CELL00166; CELL00169; CELL00156; CELL00022; CELL10119 HCC1419; HCC1395; NCIH226; NCIH446; ZR-75-1; HCC1937; HCC1187; HCC1806; BT549; NCIH520; MEFs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01150 The study proposed a model in which high expression of TYRO3 or TYRO3 activation by its ligands on apoptotic cells triggers the downstream AKT/NRF2 pathway, followed by the transcription of genes that inhibit ferroptosis in Mammary carcinoma. . . . Up regulation Suppressor Marker/Suppressor Six-week-old BALB/c mice were purchased from The Jackson Laboratory. Mouse 4T1 cells (5 x 104 cells) in 50 uL of 50% Matrigel (47743-720, Corning) were injected into the mammary fat pad. Three days after inoculation, 100 ug mouse anti-PD-1 antibody (BE0146, Bio X Cell) or IgG control (BE0089, Bio X Cell) was injected intraperitoneally twice a week for a total of 5 injections. For the TYRO3 inhibitor and antimPD-1 combination treatment, mice were also treated daily with vehicle control (90% polyethylene glycol 400 and 10% DMSO) or LDC1267 (20 mg/kg, S7638, Selleck Chemical) for 10 days by intraperitoneal injection. REF000383 ICD-11: 2C60 Mammary carcinoma CELL00540; CELL00057; CELL00007; CELL00156; CELL00038; CELL00563 4T1; 293T; B16F10; BT549; THP1; PY8119 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis; Cell proliferation
unique00025 Sulfasalazine (SAS) upregulated TFRC and DMT1. Knockdown of the ER increased TFRC expression in breast cancer cells. In conclusion SAS could trigger ferroptosis in breast cancer cells, especially in cells with low ER expression. Inducer . Up regulation . . Driver . REF000070 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00135; CELL00156; CELL00002 MDA-MB-231; T47D; BT549; MCF7 Ferroptosis (hsa04216) Cell ferroptosis
unique00908 ATM inhibition enhanced the nuclear translocation of metal-regulatory transcription factor 1 (MTF1), responsible for regulating expression of Ferritin/FPN1 and ferroptosis protection in breast adenocarcinoma. . . . Up regulation Suppressor Marker/Suppressor . REF000077 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00121; CELL00057; CELL00095 MDA-MB-231; RCC4; 293T; HT-1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00909 ATM inhibition enhanced the nuclear translocation of metal-regulatory transcription factor 1 (MTF1), responsible for regulating expression of Ferritin/FPN1 and ferroptosis protection in breast adenocarcinoma. . . . Down regulation Driver Marker/Suppressor . REF000077 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00121; CELL00057; CELL00095 MDA-MB-231; RCC4; 293T; HT-1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00004 Overexpression FPN resulted in decreased ROS and cell death whereas knockdown of FPN increased cell death after siramesine and lapatinib treatment. This indicates a novel induction of ferroptosis through altered iron regulation by treating breast cancer cells with a lysosome disruptor and a tyrosine kinase inhibitor. Inducer . Down regulation . . Marker/Suppressor . REF000013 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00003; CELL00002; CELL00019 MDA MB-231; SKBR3; MCF-7; ZR-75-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00005 Overexpression FPN resulted in decreased ROS and cell death whereas knockdown of FPN increased cell death after siramesine and lapatinib treatment. This indicates a novel induction of ferroptosis through altered iron regulation by treating breast cancer cells with a lysosome disruptor and a tyrosine kinase inhibitor. Inducer . Down regulation . . Marker/Suppressor . REF000013 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00003; CELL00002; CELL00019 MDA MB-231; SKBR3; MCF-7; ZR-75-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00677 The combined treatment of etoposide and erastin synergistically induced oxidative stress and lipid peroxidation, while suppressing glutathione peroxidase activity in breast cancer cells. More importantly, the combination treatment synergistically increased iron accumulation, which was associated with altered expression of IREB2/FPN1. Additionally, ferroptosis-regulating proteins ACSF2 and GPX4 were altered more potently by the combination treatment, compared to untreated cells and erastin treatment alone (p<0.05). Inducer . Down regulation . . Suppressor . REF000902 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00141; CELL00005 MCF-7; MCF-10A; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01431 Knockdown of circ-BGN inhibited breast cancer cell viability and notably restored its sensitivity to trastuzumab. Further, we found that circ-BGN could directly bind to OTUB1 and SLC7A11, enhancing OTUB1-mediated SLC7A11 deubiquitination and thereby inhibiting ferroptosis. . . . Up regulation Suppressor Suppressor A total of 24 NOD/SCID mice were purchased from Model Animal Research Center and grown under specific-pathogen-free condition. Mice were randomly divided into three groups (n = 8 per group), BT474-Tr cells were inoculated orthotopically onto the abdominal mammary fat pad. After 1 week, mice were treated with erastin (15 mg/kg intraperitoneal, twice every other day). Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma). To better dissolve erastin, we warmed the tube at 37 water bath and shook it gently. At the end of the sixth week, all mice were sacrificed, tumor tissues were collected and weighed. REF000673 ICD-11: 2C60-2C65 Breast cancer CELL00078; CELL00003 BT474; SKBR3 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00828 MUC1-C binds directly with CD44v and in turn promotes stability of xCT (SLC7A11) in the cell membrane in breast adenocarcinoma. The interaction between 2MUC1-C and xCT is further supported by the demonstration that targeting xCT with silencing or the inhibitor sulfasalazine suppresses MUC1 gene transcription by increasing histone and DNA methylation on the MUC1 promoter. . . . Up regulation Suppressor Suppressor . REF000009 ICD-11: 2C60 Breast adenocarcinoma CELL00112; CELL00002; CELL00057 MDA-MB-468; MCF-7; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00105 The combined effects of vorinostat with salazosulfapyridine (SASP) depend on the accumulation of ROS caused by a decrease in intracellular GSH levels, possibly due to SASP-mediated inhibition of xCT. xCT (coded by the SLC7A11 gene), a light chain subunit of the glutamate-cystine antiporter system Xc(-) in Breast adenocarcinoma. Inducer . Down regulation . . Suppressor . REF000158 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00087 MDA-MB-231; HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00310 Metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc-inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Inducer . Down regulation . . Suppressor T47D xenografts were established in 5-week-old nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 107 cells mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, Metformin, SAS, and Metformin + SAS groups). Metformin (200 mg/kg/day) was provided in drinking water. Sulfasalazine was dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 250 mg/kg once a day. REF000438 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00135; CELL00086; CELL00075; CELL00277; CELL00005; CELL00156 MCF-7; T47D; HCC1937; Bcap37; NHFB; HBL-100; MDAMB231; BT549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01265 The present study demonstrated that miR-5096 targets and downregulates SLC7A11, thereby providing a mechanistic basis for ferroptosis in human breast cancer cells. In addition, miR-5096 induced cell death via ferroptosis, characterized by mitochondrial shrinkage with partial loss of cristae with simultaneous changes in ACSL4, ROS, lipid ROS, OH-, reactive iron, GSH, and MMP levels. . . . Down regulation Driver Suppressor Mating was setup 2 days prior to injection day and zebrafish embryos were collected and incubated in E3 embryo medium (5 mM NaCl, 0.17 mM KCl, 10 mM HEPES, 0.33 mM MgSO4·7H2O, 0.33 mM CaCl2·6H2O, and 0.00001% methylene blue) containing 0.2 mM N-phenyl-thiourea (PTU) (catalog no: P7629, Sigma-Aldrich). Two days post-fertilization, the chorion was removed manually using fine forceps, and the embryos were anesthetized using E3 medium containing 200 mg/L Ethyl 3-aminobenzoate methanesulfonate (Tricaine) (catalog no: A5040, Sigma-Aldrich). Anesthetized embryos were mounted in 0.7% low melting agarose containing 200 ug/ml of Tricaine and were microinjected with 500 cells in the yolk sac using Nanoject III (catalog no: 3-000-207; Drummond Scientific Company, PA, USA). At 1 day post-injection (dpi), embryos with similar graft size were selected and imaged using both bright field and RFP channels and incubated in E3-PTU medium containing 5 ug/ml doxycycline at 34 until further imaging. At 4 dpi, embryos were anesthetized and imaged again using both bright field and RFP channels using Olympus IX-73 microscope. Cells that migrated outside the yolk sac (injection site) were represented by a notable fluorescent dot and considered a metastatic event; these were counted manually for all embryos in each experimental group. REF000513 ICD-11: 2C60-2C65 Breast cancer CELL00112; CELL00111; CELL00156; CELL00005; CELL00003; CELL00135; CELL00002; CELL00019; CELL00141 MDA-MB-468; MDA-MB-453; BT-549; MDAMB-231; SKBR-3; T-47D; MCF-7; ZR-75; MCF-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01432 Knockdown of circ-BGN inhibited breast cancer cell viability and notably restored its sensitivity to trastuzumab. Further, we found that circ-BGN could directly bind to OTUB1 and SLC7A11, enhancing OTUB1-mediated SLC7A11 deubiquitination and thereby inhibiting ferroptosis. . . . Up regulation Suppressor Suppressor A total of 24 NOD/SCID mice were purchased from Model Animal Research Center and grown under specific-pathogen-free condition. Mice were randomly divided into three groups (n = 8 per group), BT474-Tr cells were inoculated orthotopically onto the abdominal mammary fat pad. After 1 week, mice were treated with erastin (15 mg/kg intraperitoneal, twice every other day). Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma). To better dissolve erastin, we warmed the tube at 37 water bath and shook it gently. At the end of the sixth week, all mice were sacrificed, tumor tissues were collected and weighed. REF000673 ICD-11: 2C60-2C65 Breast cancer CELL00078; CELL00003 BT474; SKBR3 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01438 SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, the study elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer. . . . Down regulation Driver Suppressor . REF000679 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00019; CELL00005 MCF-7; ZR-75-1; MDA-MB-231 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01439 SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, the study elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer. . . . Up regulation Suppressor Suppressor . REF000679 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00019; CELL00005 MCF-7; ZR-75-1; MDA-MB-231 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01578 TMEM189 (PEDS1) could inhibit autophagy to mediate ferroptosis in breast cancer cells. Moreover, TMEM189 ablation strongly up-regulated LC3BII and transferrin receptor 1 (TfR1) expression levels in breast cancer cells, whereas down-regulated p62 and GPX4. . . . Down regulation Suppressor Marker/Suppressor/Driver Twenty BALB/c nude female mice (4- to 6-week-old) were purchased from Charles River Laboratories (Beijing, China) to establish tumorigenesis (5 mice in each). We injected MCF-7 or MDA-MB-231 cells (4 x 106) transfected with the stable knockdown and over-expressing TMEM189 into the flanks of mice to construct tumorigenesis models, respectively. Meanwhile, the sh-Con and empty vector were served as the control groups for each model. REF000783 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00005 MCF-7; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00024 Sulfasalazine (SAS) upregulated TFRC and DMT1. Knockdown of the ER increased TFRC expression in breast cancer cells. In conclusion SAS could trigger ferroptosis in breast cancer cells, especially in cells with low ER expression. Inducer . Up regulation . . Marker/Suppressor/Driver . REF000070 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00135; CELL00156; CELL00002 MDA-MB-231; T47D; BT549; MCF7 Ferroptosis (hsa04216) Cell ferroptosis
unique00912 In epithelial cells, such interactions mediated by E-cadherin suppress ferroptosis by activating the intracellular NF2 (also known as merlin) and Hippo signalling pathway in Breast adenocarcinoma. Antagonizing this signalling axis allows the proto-oncogenic transcriptional co-activator YAP to promote ferroptosis by upregulating several ferroptosis modulators, including ACSL4 and TFRC. . . . Up regulation Driver Marker/Suppressor/Driver Six- to eight-week-old female athymic nu/nu mice were purchased from Envigo (East Millstone, NJ, USA). For s.c. tumour models, mice were injected in the right flank with 1 x 107 shNT-GPX4 iKO MSTO-211H cells or shMerlin-GPX4 iKO MSTO-211H cells suspended in 150 uL Matrigel. Tumours were measured with callipers every 3 days. When tumours reached a mean volume of 100 mm3, mice with similarly sized tumours were grouped into four treatment groups. For control or knockout cohorts, mice were given intraperitoneal (i.p.) injections of 0.9% sterile saline or Doxycycline (100 mg/kg body weight) for two days. At the same time, mice were provided with either a normal diet or Doxycycline diet for control or knockout cohorts, respectively. REF000079 ICD-11: 2C60 Breast adenocarcinoma CELL10119; CELL10113; CELL00005; CELL00078; CELL00287 MEFs; NF639; MDA-MB-231; BT474; H1650 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique01302 Knockdown of circGFRA1 could attenuate HER-2-positive HER-2-positive breast cancer progression by inhibiting the proliferation, infiltration and migratory ability of HER-2-positive BC cells. Through ceRNA mechanism, circGFRA1 could bind to miR-1228 and alleviate inhibitory activity of miR-1228 on targeted gene AIFM2. . . . Up regulation Suppressor Suppressor Female BALB/c nude mice aged 4 weeks were administered subcutaneously with 2 x 106 cells (five mice/group). After that, the mice were given intratumoural inoculation of 40 uL si-circGFRA1 or si-NC every 4 days. To detect lung metastases, we intravenously inoculated 1 x 105 cells into the tail veins of mice (six mice/group). After the elapse of 8 weeks, we anaesthetized the mice, harvested their lungs and visually counted the metastatic nodules in the lungs, followed by validation via H&E staining and counting under a microscope. REF000552 ICD-11: 2C60-2C65 Breast cancer CELL00003; CELL00078 184A; SKBR3; BT474 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell infiltration; Cell migration
unique01303 Knockdown of circGFRA1 could attenuate HER-2-positive HER-2-positive breast cancer progression by inhibiting the proliferation, infiltration and migratory ability of HER-2-positive BC cells. Through ceRNA mechanism, circGFRA1 could bind to miR-1228 and alleviate inhibitory activity of miR-1228 on targeted gene AIFM2. . . . Down regulation Driver Suppressor Female BALB/c nude mice aged 4 weeks were administered subcutaneously with 2 x 106 cells (five mice/group). After that, the mice were given intratumoural inoculation of 40 uL si-circGFRA1 or si-NC every 4 days. To detect lung metastases, we intravenously inoculated 1 x 105 cells into the tail veins of mice (six mice/group). After the elapse of 8 weeks, we anaesthetized the mice, harvested their lungs and visually counted the metastatic nodules in the lungs, followed by validation via H&E staining and counting under a microscope. REF000552 ICD-11: 2C60-2C65 Breast cancer CELL00003; CELL00078 184A; SKBR3; BT474 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell infiltration; Cell migration
unique01495 The NF2-YAP signaling axis modulated the expression of ferroptosis suppressor protein 1 (FSP1) and CD24 in CD24 high cells. This system achieved dual antitumor effects, ultimately promoting cell death and thus inhibiting triple-negative breast cancer (TNBC) tumor growth, with some tumors even disappearing. . . . Up regulation Suppressor Suppressor C57BL/6 mice (female, 6-8 weeks old, 20-30 g weight) and SPF-grade SD rats (female, 180-230 g weight) were used to detect the toxicity of nanoparticles. Different cells (5 x 106) cells were grafted in the left flank; 5 days after engraftation, the stimulated TAMs (1 x 106) were injected into NSG mice through the tail vein. Different treatments were given and recorded as day 0. REF000718 ICD-11: 2C60 Triple-negative breast cancer CELL10109 Macrophage Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01496 The NF2- YAP signaling axis modulated the expression of ferroptosis suppressor protein 1 (FSP1) and CD24 in CD24 high cells. This system achieved dual antitumor effects, ultimately promoting cell death and thus inhibiting triple-negative breast cancer (TNBC) tumor growth, with some tumors even disappearing. . . . Down regulation Driver Suppressor C57BL/6 mice (female, 6-8 weeks old, 20-30 g weight) and SPF-grade SD rats (female, 180-230 g weight) were used to detect the toxicity of nanoparticles. Different cells (5 x 106) cells were grafted in the left flank; 5 days after engraftation, the stimulated TAMs (1 x 106) were injected into NSG mice through the tail vein. Different treatments were given and recorded as day 0. REF000718 ICD-11: 2C60 Triple-negative breast cancer CELL10109 Macrophage Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00133 BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. Inducer Down regulation . . Suppressor . Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days. REF000190 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00112; CELL00003 MDA-MB-231; MDA-MB-468; SK-BR-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00131 BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. Inducer Down regulation . . Suppressor . Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days. REF000190 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00112; CELL00003 MDA-MB-231; MDA-MB-468; SK-BR-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01835 Isoliquiritin notably counteracted the LPS-induced relative protein levels of p-p50/p50, p-p65/p65 (RELA), and IB, and the levels of ferroptosis, oxidative stress, glycolysis, and inflammation. Iso inhibited the NF-kB signaling to regulate ferroptosis and improved Dox-resistance in breast cancer. Inducer Down regulation . . Suppressor . BALB/c nude mice (4 weeks old) were obtained from Charles river (Beijing, China). Mice were fed in a temperature-controlled SPF animal room with a 12-h cycle of light-dark. All animal experiments were ratified by the Animal Research Ethics Committee of Shenzhen Bao'an Traditional Chinese Medicine Hospital Group. 10 mice were subcutaneously inoculated with a total of 2106 of MDA-MB-231 cells and then divided into two groups at random, including the Model group and Iso group. Mice in the Iso group were intraperitoneally injected with 25?mg/kg/d Iso, while mice in the Model group were supplied with the same amount of phosphate buffer saline (PBS, Beyotime). Tumor volume was monitored every 4 d. Mice were sacrificed with the intraperitoneal introduction of sodium pentobarbital (100 mg/kg) after tumor cells treatment for 31 d, and the tumor samples were removed and weighed. Tumor volume was determined according to the formula: volume = 1/2 x length x width2. REF000934 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00002 MDA-MB-231; MCF-7 Ferroptosis (hsa04216); Apoptosis (hsa04210); Gluconeogenesis (hsa00010); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00132 BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. Inducer Down regulation . . Suppressor . Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days. REF000190 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00112; CELL00003 MDA-MB-231; MDA-MB-468; SK-BR-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01088 Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), the receptor for collagen I, is highly expressed in ferroptosis-sensitive recurrent tumor cells and human mesenchymal breast cancer cells. Erastin treatment induces DDR2 upregulation and phosphorylation, independent of collagen I. Furthermore, DDR2 knockdown in recurrent tumor cells reduces clonogenic proliferation. Inducer Up regulation . . Driver . . REF000327 ICD-11: 2C60-2C65 Breast cancer CELL00434; CELL00019; CELL00078; CELL00002; CELL00077; CELL00005; CELL00010; CELL00145; CELL00156 SUM52; ZR751; BT474; MCF7 T47D; BT20; MDA-MB-231; Hs 578T, BT549; MDA-MB-157 Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell proliferation
unique00130 BET (BRD2, BRD3, BRD4, BRDT) inhibitors (BETi) exert an excellent anti-cancer activity in breast cancer. BETi JQ1 and I-BET151 exhibited anti-cancer effects in breast cancer by inducing ferroptosis. NCOA3 as a coactivator synergized with NR5A2 to prevent BETi-induced ferroptosis. Mechanistically, NR5A2 synergized with NCOA3 to increase expression of NRF2, a transcription factor that controls the expression of many antioxidant genes. Inducer Down regulation . . Suppressor . Athymic nu/nu mice (5 to 6-week-old female) were acquired from the Silaike Experimental Animal Co. Ltd (Shanghai, China). All mice were randomly allocated to different groups, 1 x 106 MDA-MB-231 cells were subcutaneously inoculated into the right flanks. Ten days later, mice were intraperitoneally injected with PBS including DMSO, JQ1 (50 mg/kg), Bufalin (1 mg/kg) and SR1848 (50 mg/kg), every 2-4 days for 8 times, and the tumor volumes and mice weigh were monitored and recorded every 2-3 days. REF000190 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00112; CELL00003 MDA-MB-231; MDA-MB-468; SK-BR-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00678 The combined treatment of etoposide and erastin synergistically induced oxidative stress and lipid peroxidation, while suppressing glutathione peroxidase activity in breast cancer cells. More importantly, the combination treatment synergistically increased iron accumulation, which was associated with altered expression of IREB2/FPN1. Additionally, ferroptosis-regulating proteins ACSF2 and GPX4 were altered more potently by the combination treatment, compared to untreated cells and erastin treatment alone (p<0.05). Inducer Up regulation . . Driver . . REF000902 ICD-11: 2C60-2C65 Breast cancer CELL00002; CELL00141; CELL00005 MCF-7; MCF-10A; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01285 Metformin and lncRNA-H19 can regulate both autophagy and ferroptosis. Autophagy inducers and H19 can reverse the production of lipid reactive oxygen species and the inhibition of autophagy induced by metformin. Metformin may induce ferroptosis by inhibiting autophagy via H19, and this discovery may facilitate the development of novel therapies for the treatment of breast cancer. Inducer Down regulation . . Suppressor . . REF000538 ICD-11: 2C60-2C65 Breast cancer CELL00002 MCF7 Glutamate metabolism (hsa00250); Autophagy (hsa04140); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique00156 The effect of the xCT (SLC7A11) inhibitor, sulfasalazine on cytotoxicity was stronger in paclitaxel-resistant uterine serous carcinoma (USC) cells compared with that in paclitaxel-sensitive USC cells. Furthermore, the synthetic lethal interaction between the accumulation of ROS and the activation of the Ras effector, JNK, induced cell-proliferation inhibition and ferroptotic cell death in paclitaxel-resistant USC cells. Inducer . Down regulation . . Suppressor The mean weight of the mice at the start was 19.4 ± 0.87 g. To generate the subcutaneous xenograft model, USPC1 (5 x 106 cells) or PTX1 (5 x 106 cells) were suspended in 200 ul of PBS following determination of cellular viability and injected into the subcutaneous tissue of 6-week-old female Crj:SHO-PrkdcscidHrhr hairless SCID mice (n = 2) (Charles River Laboratories Inc.). Tumor formation was visually confirmed in mice inoculated with USPC1 cells, but not in those inoculated with PTX1 cells, thus the animal study was performed using USPC1 cells. The recipient mice were monitored for general health status and presence of subcutaneous tumors once a week. REF000209 ICD-11: 2C72 Uterine serous carcinoma CELL10038; CELL00316; CELL00128 UCPC1; PTX1; SKOV3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01030 MiR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. . . . Down regulation Suppressor Driver . REF000247 ICD-11: 2C73 Ovarian cancer CELL00479; CELL00128 HO8910; SKOV3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01696 FZD7 was a direct target of miR-1-3p, which inhibited the expression of FZD7 by binding to the 3'-untranslated region (3'UTR) site of FZD7. In ovarian cancer tissues, overexpression of FZD7 reduced the sensitivity of platinum-resistant ovarian cancer cells to ferroptosis by up-regulating GPX4 expression. . . . Up regulation Suppressor Suppressor . REF000913 ICD-11: 2C73 Ovarian cancer CELL00329; CELL00479; CELL00128; CELL00057 HOSE; HO8910; SKOV3; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01791 Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. Inducer . Down regulation . . Suppressor . REF001016 ICD-11: 2C73 Ovarian cancer CELL00070; CELL00608 A2780; OVCAR3 Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00810 Tripterygium (TG) can effectively inhibit the proliferation of drug-resistant ovarian tumor cells A2780/DDP and increase the sensitivity to cisplatin chemotherapy both invitro and invivo. In terms of mechanism, TG induces ferroptosis by targeting the NRF2/GPX4 signal axis to weaken the antioxidant capacity of cancer cells. Inducer . Down regulation . . Suppressor All female BALB/cnude mice(4-6 weeks old, 15-20 g) were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). They were raised in specific pathogen-free conditions and allowed to access sterile water and food freely. A2780/DDP cell suspension (100 uL) with a density of 1 x 107 cells/mL was injected subcutaneously into the axilla of the mice. After observing the nude mice for a week, it was confirmed that subcutaneous A2780/DDP cells were inoculated successfully. Sterile saline (100 uL) was injected into the abdominal cavity of the nude mice in the control group for 14 days. The mice in the DDP treatment group were given DDP (4 mg/kg/day) intraperitoneally on the first and eighth days. TG (100 uL, 1 mg/kg) diluted with sterile physiological saline were injected into the abdominal cavity of the nude mice in the TG treatment group for 14 days. In addition, the nude mice in the TG + DDP treatment group were given TG (100 uL, 1 mg/kg) for 14 days and DDP (4 mg/kg/day) intraperitoneally on the first and eighth days. REF001025 ICD-11: 2C73 Ovarian cancer CELL00511 A2780/DDP Ferroptosis (hsa04216) Cell ferroptosis
unique01788 Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. Inducer . Down regulation . . Suppressor . REF001016 ICD-11: 2C73 Ovarian cancer CELL00070; CELL00608 A2780; OVCAR3 Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01695 FZD7 was a direct target of miR-1-3p, which inhibited the expression of FZD7 by binding to the 3'-untranslated region (3'UTR) site of FZD7. In ovarian cancer tissues, overexpression of FZD7 reduced the sensitivity of platinum-resistant ovarian cancer cells to ferroptosis by up-regulating GPX4 expression. . . . Down regulation Driver Suppressor . REF000913 ICD-11: 2C73 Ovarian cancer CELL00329; CELL00479; CELL00128; CELL00057 HOSE; HO8910; SKOV3; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00620 Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/HO-1/GPX4/xCT axis. Inducer . Down regulation . . Suppressor Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. REF000845 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608 SKOV3; OVCAR-3 Ferroptosis (hsa04216) Cell ferroptosis
unique01049 Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7 platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors. . . . Up regulation Suppressor Suppressor To develop platinum resistant OC cells in vivo, female (6-8 weeks old) athymic nude mice (Foxn1nu, Envigo) were injected subcutaneously (s.c.) with 2 million SKOV3 or OVCAR3 cells, or intraperitoneally (i.p.) with 2 million OVCAR5 cells to induce tumors. REF000264 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608; CELL00388; CELL00247; CELL00535; CELL00252; CELL00416 SKOV3; OVCAR3; OVCAR5; COV362; FT190; PEO1; PEO4 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01050 Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7 platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors. . . . Up regulation Suppressor Suppressor To develop platinum resistant OC cells in vivo, female (6-8 weeks old) athymic nude mice (Foxn1nu, Envigo) were injected subcutaneously (s.c.) with 2 million SKOV3 or OVCAR3 cells, or intraperitoneally (i.p.) with 2 million OVCAR5 cells to induce tumors. REF000264 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608; CELL00388; CELL00247; CELL00535; CELL00252; CELL00416 SKOV3; OVCAR3; OVCAR5; COV362; FT190; PEO1; PEO4 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00619 Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/ HO-1/GPX4/xCT axis. Inducer . Down regulation . . Suppressor Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. REF000845 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608 SKOV3; OVCAR-3 Ferroptosis (hsa04216) Cell ferroptosis
unique01790 Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. Inducer . Down regulation . . Marker/Suppressor . REF001016 ICD-11: 2C73 Ovarian cancer CELL00070; CELL00608 A2780; OVCAR3 Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00809 Tripterygium (TG) can effectively inhibit the proliferation of drug-resistant ovarian tumor cells A2780/DDP and increase the sensitivity to cisplatin chemotherapy both invitro and invivo. In terms of mechanism, TG induces ferroptosis by targeting the NRF2/GPX4 signal axis to weaken the antioxidant capacity of cancer cells. Inducer . Down regulation . . Marker/Suppressor All female BALB/cnude mice(4-6 weeks old, 15-20 g) were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). They were raised in specific pathogen-free conditions and allowed to access sterile water and food freely. A2780/DDP cell suspension (100 uL) with a density of 1 x 107 cells/mL was injected subcutaneously into the axilla of the mice. After observing the nude mice for a week, it was confirmed that subcutaneous A2780/DDP cells were inoculated successfully. Sterile saline (100 uL) was injected into the abdominal cavity of the nude mice in the control group for 14 days. The mice in the DDP treatment group were given DDP (4 mg/kg/day) intraperitoneally on the first and eighth days. TG (100 uL, 1 mg/kg) diluted with sterile physiological saline were injected into the abdominal cavity of the nude mice in the TG treatment group for 14 days. In addition, the nude mice in the TG + DDP treatment group were given TG (100 uL, 1 mg/kg) for 14 days and DDP (4 mg/kg/day) intraperitoneally on the first and eighth days. REF001025 ICD-11: 2C73 Ovarian cancer CELL00511 A2780/DDP Ferroptosis (hsa04216) Cell ferroptosis
unique00618 Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/HO-1/GPX4/xCT axis. Inducer . Down regulation . . Marker/Suppressor Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. REF000845 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608 SKOV3; OVCAR-3 Ferroptosis (hsa04216) Cell ferroptosis
unique01787 Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. Inducer . Down regulation . . Marker/Suppressor . REF001016 ICD-11: 2C73 Ovarian cancer CELL00070; CELL00608 A2780; OVCAR3 Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01816 NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 (SLC16A1) and activate the AMPK signaling pathway in ovarian cancer cells, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression. Inducer . Down regulation . . Suppressor BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days. REF001046 ICD-11: 2C73 Ovarian cancer CELL00532; CELL00341 Anglne; HO8910PM Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis; Cell proliferation
unique01456 ADAMTS9-AS1 regulated SLC7A11 expression through miR-587, thereby affecting ferroptosis, proliferation and migration of Epithelial ovarian cancer cells. . . . Up regulation Suppressor Suppressor . REF000690 ICD-11: 2C73 Epithelial ovarian cancer CELL00263; CELL00608; CELL00079 ES-2; OVCAR3; CAOV-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01717 circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in ovarian cancer. . . . Up regulation Suppressor Suppressor . REF000937 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00070 SKOV3; A2780 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01321 KLHDC3 expression is elevated in ovarian cancer. KLHDC3 suppresses ferroptosis in vitro and supports tumor growth in vivo by relieving p14ARF-mediated suppression of SLC7A11 transcription. . . . Up regulation Suppressor Suppressor 4-6-week-old female BALB/c nu/nu mice obtained from SLAC Laboratory Animal Co., Ltd. were bred and maintained in our institutional pathogen-free mouse facilities. Ovarian tumors were established by subcutaneously injecting 5 x 106 SKOV3 cells in 100 ul of PBS buffer into the right flank of 6-week-old nude mice (four mice for each group). At the end of 3 weeks, mice were killed and in vivo solid tumors were dissected and weighed. REF000574 ICD-11: 2C73 Ovarian cancer CELL00057; CELL00056; CELL00128; CELL00608; CELL00220; CELL00049; CELL00012; CELL00002; CELL00045; CELL00098; CELL00561; CELL00304; CELL00299 293T; H1299; SKOV3; OVCAR-3; SJSA; HeLa; Huh-7; MCF-7; A549; Hep3B; CT26; L02; HCCLM3 Ubiquitin mediated proteolysis (hsa04120); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell growth
unique01457 ADAMTS9-AS1 regulated SLC7A11 expression through miR-587, thereby affecting ferroptosis, proliferation and migration of Epithelial ovarian cancer cells. . . . Down regulation Driver Suppressor . REF000690 ICD-11: 2C73 Epithelial ovarian cancer CELL00263; CELL00608; CELL00079 ES-2; OVCAR3; CAOV-3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01718 circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in ovarian cancer. . . . Down regulation Driver Suppressor . REF000937 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00070 SKOV3; A2780 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01112 Mechanistically, pharmacological inhibition or genetic deletion of PARP1 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP1 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01119 Mechanistically, pharmacological inhibition or genetic deletion of PARP10 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP10 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01120 Mechanistically, pharmacological inhibition or genetic deletion of PARP11 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP11 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01121 Mechanistically, pharmacological inhibition or genetic deletion of PARP12 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP12 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01122 Mechanistically, pharmacological inhibition or genetic deletion of PARP14 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP14 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01123 Mechanistically, pharmacological inhibition or genetic deletion of PARP15 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP15 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01124 Mechanistically, pharmacological inhibition or genetic deletion of PARP16 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP16 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01113 Mechanistically, pharmacological inhibition or genetic deletion of PARP2 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP2 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01114 Mechanistically, pharmacological inhibition or genetic deletion of PARP3 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP3 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01115 Mechanistically, pharmacological inhibition or genetic deletion of PARP4 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP4 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01116 Mechanistically, pharmacological inhibition or genetic deletion of PARP6 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP6 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01117 Mechanistically, pharmacological inhibition or genetic deletion of PARP8 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP8 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01118 Mechanistically, pharmacological inhibition or genetic deletion of PARP9 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP9 is the primary therapeutic strategy for BRCA mutant ovarian cancer. . . . Up regulation Suppressor Suppressor Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 106 A2780 or 1 x 106 HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm3. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. REF000357 ICD-11: 2C73 Ovarian cancer CELL00091; CELL00070; CELL00128; CELL00057 HEY; A2780; SKOV3; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique00621 Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/HO-1/GPX4/xCT axis. Inducer . Down regulation . . Suppressor Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. REF000845 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608 SKOV3; OVCAR-3 Ferroptosis (hsa04216) Cell ferroptosis
unique00176 The MI463 induced decrease in cell viability may be at least partly associated with the inhibition of SCD1 activity. In addition, the potent induction of HO1 contributed to the synergistic effects of MI463 plus auranofin. Therefore, meninMLL inhibitors, such as MI463, in combination with auranofin represent an effective therapeutic approach for several types of cancer via the induction of ferroptosis in High grade ovarian serous adenocarcinoma. Inducer . Down regulation . . Suppressor . REF000234 ICD-11: 2C73 High grade ovarian serous adenocarcinoma CELL00211; CELL00608; CELL00210; CELL00045; CELL00425; CELL00371; CELL00503; CELL00156; CELL00112; CELL00005; CELL00002; CELL00135; CELL00013; CELL00120; CELL00008; CELL00160 OVCAR-8; OVCAR-3; OVCAR-4; A549; LU99; LU65; PC-7; BT-549; MDA-MB-468; MDA-MB-231; MCF-7; T47D; MIAPaCa-2; PANC-1; BxPC-3; CFPAC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00611 The mechanism results confirmed that ropivacaine inactivated the PI3K/AKT signaling pathway in ovarian cancer cells. Furthermore, in vivo assay demonstrated that ropivacaine repressed the proliferation of ovarian cancer cells in vivo and had a protective function in ovarian cancer. Inducer Down regulation . . Suppressor . Twelve Nude female BALB/c-nu mice (5-weeks-old) were from Shanghai Lab. Animal Research Center (Shanghai, China). SKOV3 cells (5 x 106) were injected subcutaneously into mice according to the previously described methods with minor changes. To evaluate the effect of ropivacaine on the growth of ovarian cancer, ropivacaine (10 mg/kg) was injected intraperitoneally into mice referring to the previously reported methods with minor revisions. The size of the tumor was measured every day and the tumor volumes were calculated by the formula: length x width2/2 = tumor volume (mm3). When the tumor size reached 2000 mm3, all mice were sacrificed and the excised tumor tissues were weighed to evaluate the antitumor effect. REF000837 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608 SKOV3; OVCAR-3 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00612 The mechanism results confirmed that ropivacaine inactivated the PI3K/AKT signaling pathway in ovarian cancer cells. Furthermore, in vivo assay demonstrated that ropivacaine repressed the proliferation of ovarian cancer cells in vivo and had a protective function in ovarian cancer. Inducer Down regulation . . Suppressor . Twelve Nude female BALB/c-nu mice (5-weeks-old) were from Shanghai Lab. Animal Research Center (Shanghai, China). SKOV3 cells (5 x 106) were injected subcutaneously into mice according to the previously described methods with minor changes. To evaluate the effect of ropivacaine on the growth of ovarian cancer, ropivacaine (10 mg/kg) was injected intraperitoneally into mice referring to the previously reported methods with minor revisions. The size of the tumor was measured every day and the tumor volumes were calculated by the formula: length x width2/2 = tumor volume (mm3). When the tumor size reached 2000 mm3, all mice were sacrificed and the excised tumor tissues were weighed to evaluate the antitumor effect. REF000837 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608 SKOV3; OVCAR-3 PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01792 Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. Inducer Up regulation . . Driver . . REF001016 ICD-11: 2C73 Ovarian cancer CELL00070; CELL00608 A2780; OVCAR3 Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01789 Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. Inducer Up regulation . . Driver . . REF001016 ICD-11: 2C73 Ovarian cancer CELL00070; CELL00608 A2780; OVCAR3 Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01097 Silencing of PTPN18 induced ferroptosis in KLE endometrial cancer cells. PTPN18 knockdown increased intracellular ROS level and down-regulated GPX4 and xCT expression. Besides, silencing of PTPN18 also induced the expression of p-p38 (MAPK14). . . . Up regulation Suppressor Suppressor . REF000338 ICD-11: 2C76 Corpus uteri cancer CELL00181 KLE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01098 Silencing of PTPN18 induced ferroptosis in KLE endometrial cancer cells. PTPN18 knockdown increased intracellular ROS level and down-regulated GPX4 and xCT expression. Besides, silencing of PTPN18 also induced the expression of p-p38 (MAPK14). . . . Down regulation Driver Suppressor . REF000338 ICD-11: 2C76 Corpus uteri cancer CELL00181 KLE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00302 Juglone as a natural quinone from C. cathayensisgreen peel could exert its anti-cancer activity by inducing iron dependent autophagy and inhibiting the migration of endometrial cancer (EC) cells. Subsequently, Fe2+ accumulation, lipid peroxidation, GSH depletion, the upregulation of HMOX1, and heme degradation to Fe2+ were reported. Juglone was involved in inducing autophagy and inhibiting cell migration and endoplasmic reticulum stress. Inducer . Up regulation . . Driver/Suppressor . REF000425 ICD-11: 2C76 Corpus uteri cancer CELL00024 EC Ishikawa cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell migration
unique01635 CircRAPGEF5 interacts with RBFOX2, an important splicing regulator, to modulate the splicing of TFRC pre-mRNA. Importantly, circRAPGEF5 promotes exon-4 skipping of TFRC by sequestering RBFOX2, resulting in resistance to ferroptosis via the reduction of labile iron in endometrial cancer cells. . . . Down regulation Suppressor Marker/Suppressor/Driver Female 4-week-old BALB/c-nu nude mice were purchased from Vital River (Beijing, China) and housed in a specific pathogen-free facility. EC cells were washed twice with serum-free medium and injected subcutaneously into nude mice (5 x 106 cells/site). Tumors were measured with calipers every four days for four weeks. The mice were sacrificed on day 32 after cell implantation, and the tumors were excised and weighed. REF000849 ICD-11: 2C76 Corpus uteri cancer CELL00181; CELL00024; CELL00089; CELL00090; CELL00123 KLE; Ishikawa; HEC-1-A; HEC-1-B; RL95-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01636 CircRAPGEF5 interacts with RBFOX2, an important splicing regulator, to modulate the splicing of TFRC pre-mRNA. Importantly, circRAPGEF5 promotes exon-4 skipping of TFRC by sequestering RBFOX2, resulting in resistance to ferroptosis via the reduction of labile iron in endometrial cancer cells. . . . Up regulation Driver Marker/Suppressor/Driver Female 4-week-old BALB/c-nu nude mice were purchased from Vital River (Beijing, China) and housed in a specific pathogen-free facility. EC cells were washed twice with serum-free medium and injected subcutaneously into nude mice (5 x 106 cells/site). Tumors were measured with calipers every four days for four weeks. The mice were sacrificed on day 32 after cell implantation, and the tumors were excised and weighed. REF000849 ICD-11: 2C76 Corpus uteri cancer CELL00181; CELL00024; CELL00089; CELL00090; CELL00123 KLE; Ishikawa; HEC-1-A; HEC-1-B; RL95-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00538 Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling. Inducer . . . Suppressor . . REF000748 ICD-11: 2C76 Corpus uteri cancer CELL10060; CELL00181 ESC; KLE mTOR signaling pathway (hsa04150); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00539 Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling. Inducer . . . Driver . . REF000748 ICD-11: 2C76 Corpus uteri cancer CELL10060; CELL00181 ESC; KLE mTOR signaling pathway (hsa04150); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01463 CircLMO1 acted as a competing endogenous RNA (ceRNA) by sponging miR-4192 to repress target gene ACSL4. CircLMO1 promoted cervical cancer cell ferroptosis through up-regulating ACSL4 expression. Overexpression of miR-4291 or knockdown of ACSL4 reversed the effect of circLMO1 on facilitating ferroptosis and repressing cervical cancer cell proliferation and invasion. . . . Up regulation Driver Driver Male BALB/c nude mice (6 weeks old) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). The mice were kept in a constant temperature (25) and pathogen-free room with free access to food and water ad libitum. The animal experiments were approved by the Ethics Committee for Animal Experimentation of The Second Affiliated Hospital and Yuying Childrens Hospital. Mice were euthanised with isoflurane inhalation. CaSki cells overexpressing circLMO1 (7 x 106 cells/100 uL PBS) were injected subcutaneously into the flank of mice. Tumor growth was measured with a caliper 3 times a week and tumor-bearing mice were euthanised at 5 weeks after inoculation. REF000694 ICD-11: 2C77.Z Cervical cancer CELL00050; CELL00049; CELL00157; CELL00359 SiHa; HeLa; CaSki; C33A Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique00242 Oleanolic acid (OA) significantly reduced the viability and proliferative capacity of Hela cells. OA activated ferroptosis in Hela cells by promoting ACSL4 expression, thereby reducing the survival rate of Hela cells. Therefore, promotion of ACSL4-dependent ferroptosis by OA may be a potential approach for the treatment of cervical cancer. Inducer . Up regulation . . Driver Male BALB/c Nude mice (20 ± 2g, 5 weeks old) were supplied by Hangzhou Ziyuan Experimental Animal Technology Co. LTD (SYXK-20180049) for this study. The nude mice were kept under specefic pathogen free (SPF) conditions for one week, and 5x107 Hela cells were injected under the left axillary skin after acclimatization. The tumors of Hela cell-inoculated mice were measured every 3 days after modeling, and tumor>=0.5 cm in diameter were considered successful. The tumor-bearing mice were randomly divided into control group (n = 6), 40 mg/kg OA group (n = 6) and 80 mg/kg OA group (n = 6). 40 mg/kg OA group and 80 mg/kg OA group both received subcutaneous injection modeling and control mice received saline intraperitoneal injections. The 40 mg/kg OA group and 80 mg/kg OA group received daily intraperitoneal injections of 40 mg/kg OA and 80 mg/kg OA for 15 days. REF000316 ICD-11: 2C77.Z Cervical cancer CELL00049 Hela Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01464 CircLMO1 acted as a competing endogenous RNA (ceRNA) by sponging miR-4192 to repress target gene ACSL4. CircLMO1 promoted cervical cancer cell ferroptosis through up-regulating ACSL4 expression. Overexpression of miR-4291 or knockdown of ACSL4 reversed the effect of circLMO1 on facilitating ferroptosis and repressing cervical cancer cell proliferation and invasion. . . . Down regulation Suppressor Driver Male BALB/c nude mice (6 weeks old) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). The mice were kept in a constant temperature (25) and pathogen-free room with free access to food and water ad libitum. The animal experiments were approved by the Ethics Committee for Animal Experimentation of The Second Affiliated Hospital and Yuying Childrens Hospital. Mice were euthanised with isoflurane inhalation. CaSki cells overexpressing circLMO1 (7 x 106 cells/100 uL PBS) were injected subcutaneously into the flank of mice. Tumor growth was measured with a caliper 3 times a week and tumor-bearing mice were euthanised at 5 weeks after inoculation. REF000694 ICD-11: 2C77.Z Cervical cancer CELL00050; CELL00049; CELL00157; CELL00359 SiHa; HeLa; CaSki; C33A Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique01215 Knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount in Endocervical adenocarcinoma. . . . Down regulation Suppressor Driver . REF000474 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00216 HeLa; SAS Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01580 miR-193a-5p was able to target GPX4 and circACAP2 promoted GPX4 expression by sponging miR-193a-5p in cervical cancer cells.Therefore, we concluded that circular RNA circACAP2 repressed ferroptosis of cervical cancer during malignant progression by miR-193a-5p/GPX4. . . . Down regulation Driver Suppressor . REF000784 ICD-11: 2C77.Z Cervical cancer CELL00050; CELL00049 SiHa; HeLa Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00791 Dihydroartemisinin (DHA) treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis. Inducer . Down regulation . . Suppressor . REF001012 ICD-11: 2C77.Z Cervical cancer CELL00049; CELL00050 HeLa; SiHa Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01579 miR-193a-5p was able to target GPX4 and circACAP2 promoted GPX4 expression by sponging miR-193a-5p in cervical cancer cells.Therefore, we concluded that circular RNA circACAP2 repressed ferroptosis of cervical cancer during malignant progression by miR-193a-5p/GPX4. . . . Up regulation Suppressor Suppressor . REF000784 ICD-11: 2C77.Z Cervical cancer CELL00050; CELL00049 SiHa; HeLa Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00790 Dihydroartemisinin (DHA) treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis. Inducer . Up regulation . . Driver . REF001012 ICD-11: 2C77.Z Cervical cancer CELL00049; CELL00050 HeLa; SiHa Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01078 CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis. . . . Up regulation Suppressor Suppressor The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. REF000312 ICD-11: 2C77.Z Cervical cancer CELL00157; CELL00049; CELL10023 CaSki; HeLa; HcerEpic Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01079 CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1- miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis. . . . Down regulation Driver Suppressor The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. REF000312 ICD-11: 2C77.Z Cervical cancer CELL00157; CELL00049; CELL10023 CaSki; HeLa; HcerEpic Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01080 CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/ 409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis. . . . Down regulation Driver Suppressor The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. REF000312 ICD-11: 2C77.Z Cervical cancer CELL00157; CELL00049; CELL10023 CaSki; HeLa; HcerEpic Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01081 CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/409-3P/ 515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis. . . . Down regulation Driver Suppressor The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. REF000312 ICD-11: 2C77.Z Cervical cancer CELL00157; CELL00049; CELL10023 CaSki; HeLa; HcerEpic Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01330 Testicular cancers are among the most common malignancies in young males. The loss of CCDC6 was associated with an enhancement of the xCT/SLC7A11 cystine antiporter expression which, by promoting the accumulation of ROS, interfered with the activation of ferroptosis pathway. . . . Down regulation Driver Suppressor . REF000595 ICD-11: 2C80 Testicular cancer CELL00334; CELL00559; CELL00448; CELL00449 NTERA-2; TM4; GC-1; GC-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01759 The regulation of ferroptosis by the RB1/E2F/ACSL4 axis and highlight the therapeutic potential of ferroptosis induction in the treatment of RB1 loss driven prostate cancer growth and metastasis and perhaps other RB1-deficient malignancies. . . . Down regulation Suppressor Driver 1 x 106 shCT or shRB PC-3 cells were mixed with 100 uL Matrigel (Corning) and implanted subcutaneously into the right flanks of 6- to 8-week-old male nude mice. When tumor volumes were approximately 80-100 mm3 in PC3 xenografts or circulating RFP tumor cells had begun to emerge in peripheral blood of PPR-RFP mice (around 7.5 months), vehicle or JKE-1674 (25 mg/kg, dissolved in 10% ethanol and 90% PEG-400, Sigma-Aldrich) were administered orally to mice every other day. REF000986 ICD-11: 2C82 Prostate cancer CELL00108; CELL00051; CELL00150; CELL00065; CELL00283; CELL00045; CELL00048; CELL00002; CELL00271; CELL00057 LNCaP; PC-3; 22Rv1; DU145; C4-2; A549; HepG2; MCF7; RWPE-1; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique01409 MiR-15a induces ferroptosis by regulating GPX4 in prostate cancer cells, which provides evidence for investigating the therapeutic strategies of prostate cancer. . . . Down regulation Driver Suppressor . REF000652 ICD-11: 2C82 Prostate cancer CELL00108 LNCAP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00237 ITC-ARi 13 and buthionine sulfoximine (BSO) cooperatively downregulate AR and induce ferroptosis likely through increasing the accessibility of 13/12b to cellular targets, escalating free intracellular ferrous iron and attenuating GSH-centered cellular defense and adaptation. Further studies on the combination of ITC-ARi and GSH synthesis inhibitor could result in a new modality against castration-resistant prostate cancer (CRPC). Collectively, the combination of ITC-ARi 13 and BSO reveals a pro-ferroptotic role of Nrf2 through upregulating HO-1 under GSH-deficient conditions. Inducer . Down regulation . . Suppressor . REF000305 ICD-11: 2C82 Castration-resistant prostate cancer CELL00408; CELL00108; CELL00283; CELL00150; CELL00271; CELL00298 VCaP; LNCaP; C42; 22Rv1; RWPE-1; MDA-kb2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00238 ITC-ARi 13 and buthionine sulfoximine (BSO) cooperatively downregulate AR and induce ferroptosis likely through increasing the accessibility of 13/12b to cellular targets, escalating free intracellular ferrous iron and attenuating GSH-centered cellular defense and adaptation. Further studies on the combination of ITC-ARi and GSH synthesis inhibitor could result in a new modality against castration-resistant prostate cancer (CRPC). Collectively, the combination of ITC-ARi 13 and BSO reveals a pro-ferroptotic role of Nrf2 through upregulating HO-1 under GSH-deficient conditions. Inducer . Up regulation . . Driver/Suppressor . REF000305 ICD-11: 2C82 Castration-resistant prostate cancer CELL00408; CELL00108; CELL00283; CELL00150; CELL00271; CELL00298 VCaP; LNCaP; C42; 22Rv1; RWPE-1; MDA-kb2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00993 PANX2 is implicated in the pathogenesis of prostate cancer (PCa), which regulates malignant phenotypes and ferroptosis through Nrf2 signaling pathway (Nrf2, HO-1, and FTH1), and maybe a potential therapeutic target for PCa. Blocking expression of PANX2 resulted in suppression of proliferation, migration, and invasion in PCa cells, while increasing ferrous iron and MDA levels. . . . Up regulation Suppressor Marker/Suppressor . REF000191 ICD-11: 2C82 Prostate cancer CELL00108; CELL00051; CELL00065; CELL00271 LNCap; PC-3; DU145; RWPE1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01180 OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, lncRNA OIP5-AS1 promotes prostate cancer progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling. . . . Up regulation Suppressor Suppressor A total of 2 x 106 PC3 and PC3/Cd cells were subcutaneously injected into the right flanks of 4-week-old male Balb/c nude mice. Tumor burdens were closely monitored by tumor volumes. When the largest tumors reached a size of 1.0 cm3, all mice were sacrificed due to ethical considerations. Moreover, the final tumor weight was also recorded. REF000420 ICD-11: 2C82 Prostate cancer CELL00051; CELL00065 PC3; DU145 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique01488 Docetaxel (DTX)-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNAPCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance. . . . Up regulation Suppressor Suppressor PC3 and PC3/DR cells (5 x 106 cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm3, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. REF000714 ICD-11: 2C82 Prostate cancer CELL00051; CELL00150 PC3; 22RV1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01489 Docetaxel (DTX)-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNAPCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance. . . . Up regulation Suppressor Suppressor PC3 and PC3/DR cells (5 x 106 cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm3, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. REF000714 ICD-11: 2C82 Prostate cancer CELL00051; CELL00150 PC3; 22RV1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01487 Docetaxel (DTX)-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNAPCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance. . . . Down regulation Driver Suppressor PC3 and PC3/DR cells (5 x 106 cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm3, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. REF000714 ICD-11: 2C82 Prostate cancer CELL00051; CELL00150 PC3; 22RV1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01486 DTX-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNA PCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance. . . . Up regulation Suppressor Suppressor PC3 and PC3/DR cells (5 x 106 cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm3, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. REF000714 ICD-11: 2C82 Prostate cancer CELL00051; CELL00150 PC3; 22RV1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01181 OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, lncRNA OIP5-AS1 promotes prostate cancer progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling. . . . Down regulation Driver Suppressor A total of 2 x 106 PC3 and PC3/Cd cells were subcutaneously injected into the right flanks of 4-week-old male Balb/c nude mice. Tumor burdens were closely monitored by tumor volumes. When the largest tumors reached a size of 1.0 cm3, all mice were sacrificed due to ethical considerations. Moreover, the final tumor weight was also recorded. REF000420 ICD-11: 2C82 Prostate cancer CELL00051; CELL00065 PC3; DU145 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique00200 Flubendazole is a novel P53 inducer which exerts anti-proliferation and pro-apoptosis effects in castration-resistant prostate cancer (CRPC) through hindering the cell cycle and activating the ferroptosis, and indicates that a novel utilization of flubendazole in neoadjuvant chemotherapy of CRPC. Inducer Up regulation . . Driver . 24 nude mice (3-4 weeks) were acquired from the experimental animal center of southern medical university (GuangZhou, China) and kept under specific pathogen-free conditions. 4 x 106 PC3 cells were implanted subcutaneously into the right armpit regions of each nude mouse. When the tumors volume reached approximately 40 mm3, mice were randomly divided into two groups to receive flubendazole (10 mg/kg, once daily), 5-fluorouracil (30 mg/kg, once daily), their combination, and vehicle control by intraperitoneal injection. After 20 days of treatment, all mice were sacrificed and tumor weight and tumor volume were immediately measured, respectively. REF000265 ICD-11: 2C82 Castration-resistant prostate cancer CELL00051; CELL00065; CELL00304; CELL00271 PC3; DU145; HL-7702; RWPE-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00385 Lycorine could inhibit the proliferation in human renal cell carcinoma (RCC) cells. The anti-tumor effect of lycorine was associated with the induction of ferroptosis. After lycorine treatment, the expression levels of GPX4 in RCC cells decreased, whereas those of ACSL4 increased. Inducer . Up regulation . . Driver . REF000521 ICD-11: 2C90 Renal cell carcinoma CELL00021; CELL00153; CELL00081; CELL00093 786-O; A498; Caki-1; HK-2 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00860 Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by inactivation of the Krebs cycle enzyme fumarate hydratase (FH). Mechanistically, the FH sensitivity to ferroptosis is attributed to dysfunctional GPX4, the primary cellular defender against ferroptosis. . . . Up regulation Suppressor Suppressor . REF000042 ICD-11: 2C90 Hereditary leiomyomatosis and renal cell cancer CELL00400; CELL00093; CELL00095 UOK262; HK2; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00861 Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by inactivation of the Krebs cycle enzyme fumarate hydratase (FH). Mechanistically, the FH sensitivity to ferroptosis is attributed to dysfunctional GPX4, the primary cellular defender against ferroptosis. . . . Up regulation Suppressor Suppressor . REF000042 ICD-11: 2C90 Renal cell carcinoma CELL00400; CELL00093; CELL00095 UOK262; HK2; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00384 Lycorine could inhibit the proliferation in human renal cell carcinoma (RCC) cells. The anti-tumor effect of lycorine was associated with the induction of ferroptosis. After lycorine treatment, the expression levels of GPX4 in RCC cells decreased, whereas those of ACSL4 increased. Inducer . Down regulation . . Suppressor . REF000521 ICD-11: 2C90 Renal cell carcinoma CELL00021; CELL00153; CELL00081; CELL00093 786-O; A498; Caki-1; HK-2 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01249 Analysis of clinical specimens revealed that there is a close correlation between KLF2 and GPX4 in clear cell renal cell carcinoma (ccRCC). Mechanistically, KLF2 deficiency is sufficient to inhibit ferroptosis on account of the impairment of transcriptional repression of GPX4 and thus promotes the migration and invasion of RCC cells. . . . Down regulation Driver Suppressor BALB/c mice were purchased from the Animal Core Facility of Nanjing Medical University. Injection into the tail vein of 6-week-old male mice with Renca-luci (luciferase) cells (1 x 105 cells) was adopted to build the model oflung metastasis. Before lungs were harvested after 1 month to assess pulmonary metastasis, lung metastatic nodules were tracked with IVIS spectrum imaging system in vivo or not (n = 5/group). For survival analysis, the time of death was recorded in each group (n = 10/group) after cells were injected. For assessing the effect of liproxstatin-1 (Lipro, Sigma), one week after injection of cells in the tail vein, mice were tail intravenous administrated with 2.5 mg/kg Lipro three times on a weekly basis for two weeks, then lungs were harvested ( n= 5/group). REF000498 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00057; CELL00093; CELL00021; CELL00151; CELL00155; CELL00081 293T; HK-2; 786-O; 769-P; ACHN; Caki-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01167 DHODH operates in parallel to mitochondrial GPX4 (but independently of cytosolic GPX4 or FSP1) to inhibit ferroptosis in the mitochondrial inner membrane by reducing ubiquinone to ubiquinol (a radical-trapping antioxidant with anti-ferroptosis activity) in Clear cell renal carcinoma. . . . Up regulation Suppressor Suppressor 5 x 106 HT-1080 or 1 x 107 NCI-H226 cells were injected into mice subcutaneously. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups. Brequinar or sulfasalazine was dissolved in dimethyl sulfoxide (DMSO) and diluted in PBS. Brequinar was intraperitoneally injected into mice at a dose of 30 mg/kg every three days. Sulfasalazine was intraperitoneally injected daily at a dose of 100 mg/kg. Liproxstatin-1 diluted in PBS was intraperitoneally injected daily at a dose of 10 mg/kg. The daily injection of brequinar, sulfasalazine, or liproxstatin-1 was continued until the endpoint as indicated in the corresponding figures. REF000404 ICD-11: 2C90 Clear cell renal carcinoma CELL00417; CELL00418; CELL00121; CELL00229; CELL00095; CELL00198 UMRC2; UMRC6; RCC4; TK-10; HT-1080; NCI-H226 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00187 Tetrachlorobenzoquinone (TCBQ)-induced ferroptosis occurred as a result of iron accumulation and inhibition of GPX4 expression. Mechanistically, TCBQ promotes the iron import into cells by improving the expression of TF and TFR1, and the complex of TF and TFR1 is internalized by endocytosis in Adrenal gland pheochromocytoma. Inducer . Down regulation . . Suppressor . REF000246 ICD-11: 2C90 Adrenal gland pheochromocytoma CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01111 Pharmacologic inhibition of mTORC1 ( mTOR associated protein, MLST8) decreases GPX4 protein levels, sensitizes renal cell carcinoma cells to ferroptosis, and synergizes with ferroptosis inducers to suppress patient-derived xenograft tumor growth in vivo. . . . Up regulation Suppressor Suppressor PDX tumor derived from lung cancer patient rinsed in cold DMEM media were minced into fragments 1-2 mm3 in volume. Then tumor fragment was subcutaneously inoculated into the dorsal flank of NSG mice. The tumor growth in mice was monitored by bi-dimensional tumor measurements. When tumors grew to a volume of 200 mm3, the mice were divided randomly into four groups (n = 5/group) and treated with vehicle, 10 mg/kg AZD8055, 30 mg/kg IKE, or both (10% dimethyl sulfoxide/90% corn oil) by daily intraperitoneal administration. Body weights of mice in each group during treatment were also recorded accordingly. REF000355 ICD-11: 2C90 Renal cell carcinoma CELL00418; CELL00057; CELL00021; CELL00155; CELL00198; CELL00015; CELL00199; CELL00056 UMRC6; HEK293T; 786-0; ACHN; NCI-H226; H460; NCI-H23; NCI-H1299 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00920 Cell density-regulated ferroptosis is mediated by TAZ through the regulation of EMP1-NOX4, suggesting its therapeutic potential for renal cell carcinoma (RCC) and other TAZ-activated tumors. . . . Up regulation Driver Driver One million 786O cells with or without shTAZ were implanted subcutaneously into the healthy 8-week-old JAX NOD.CB17-PrkdcSCID-J mice; both male and female mice were used. Once tumor volume reached 120 mm3, mice were randomized into control or erastin treatment group. The vehicle (ORA-plus) or erastin (0.1 ml of 4 mg/ml erastin) was administrated by oral gavage twice daily for 20 days. REF000088 ICD-11: 2C90 Renal cell carcinoma CELL00121; CELL00021; CELL00057; CELL00005 RCC4; 786O; HEK293T; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis
unique00921 Cell density-regulated ferroptosis is mediated by TAZ through the regulation of EMP1-NOX4, suggesting its therapeutic potential for renal cell carcinoma (RCC) and other TAZ-activated tumors. . . . Up regulation Driver Driver One million 786O cells with or without shTAZ were implanted subcutaneously into the healthy 8-week-old JAX NOD.CB17-PrkdcSCID-J mice; both male and female mice were used. Once tumor volume reached 120 mm3, mice were randomized into control or erastin treatment group. The vehicle (ORA-plus) or erastin (0.1 ml of 4 mg/ml erastin) was administrated by oral gavage twice daily for 20 days. REF000088 ICD-11: 2C90 Renal cell carcinoma CELL00121; CELL00021; CELL00057; CELL00005 RCC4; 786O; HEK293T; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis
unique01798 USP35 functions to maintain NRF2 levels by catalyzing its deubiquitylation and thus antagonizing degradation. NRF2 reduction imposed by USP35 silencing rendered renal clear cell carcinoma cells increased sensitivity to ferroptosis induction. . . . Up regulation Suppressor Marker/Suppressor Female Balb/c nude mice aged 6 weeks were obtained from Vital River Laboratory (Beijing, China). To generate xenografts of RCC, mice were randomized into two groups of 8 that were subcutaneously inoculated with 1 x 10^7 of OS-RC-2 cells stably transfected with USP35 Tet-on shRNA constructs or empty vector. After 7 days, mice were administered with doxycycline every day (20 mg/kg) to induce shRNA expression through oral gavage without blinding. REF001028 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00021; CELL00057; CELL00151; CELL00387 RCC 786-O; HEK293T; RCC 769-P; OS-RC-2 Ubiquitin mediated proteolysis (hsa04120); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01533 The miR-4735-3p mimic increased, while the miR-4735-3p inhibitor decreased oxidative stress, lipid peroxidation, iron overload, and ferroptosis of human Clear cell renal cell carcinoma (ccRCC) cell lines. Mechanistic studies identified SLC40A1 as a direct target of miR-4735-3p. . . . Down regulation Driver Marker/Suppressor . REF000752 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00021; CELL00153; CELL00093 796-O; A498; HK2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01605 MITD1 knockdown inhibited clear cell renal cell carcinoma (ccRCC) cell proliferation and migration and induced ferroptosis in ccRCC. Subsequent overexpression experiments demonstrated that MITD1 knockdown induced ferroptosis and suppressed tumor growth and migration through the TAZ/SLC7A11 pathway. . . . Up regulation Suppressor Suppressor . REF000812 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00093; CELL00021; CELL00155; CELL00153; CELL00151; CELL00081 HK-2; 786-O; ACHN; A498; 769-P; Caki-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01414 SLC16A1-AS1 served as a sponge of miR-143-3p, and knockdown SLC16A1-AS1 significantly increased the enrichment of miR-143-3p. And then, SLC7A11 was identified as the target protein of miR-143-3p, and overexpression miR-143-3p remarkably inhibited the expression of SLC7A11. And silencing lncRNA SLC16A1-AS1 can induce ferroptosis through miR-143-3p/SLC7A11 signaling in renal cell carcinoma. . . . Up regulation Suppressor Suppressor . REF000663 ICD-11: 2C90 Renal cell carcinoma CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01415 SLC16A1-AS1 served as a sponge of miR-143-3p, and knockdown SLC16A1-AS1 significantly increased the enrichment of miR-143-3p. And then, SLC7A11 was identified as the target protein of miR-143-3p, and overexpression miR-143-3p remarkably inhibited the expression of SLC7A11. And silencing lncRNA SLC16A1-AS1 can induce ferroptosis through miR-143-3p/SLC7A11 signaling in renal cell carcinoma. . . . Down regulation Driver Suppressor . REF000663 ICD-11: 2C90 Renal cell carcinoma CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique00188 Tetrachlorobenzoquinone (TCBQ)-induced ferroptosis occurred as a result of iron accumulation and inhibition of GPX4 expression. Mechanistically, TCBQ promotes the iron import into cells by improving the expression of TF and TFR1, and the complex of TF and TFR1 is internalized by endocytosis in Adrenal gland pheochromocytoma. Inducer . Up regulation . . Marker/Suppressor/Driver . REF000246 ICD-11: 2C90 Adrenal gland pheochromocytoma CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00264 Arsenite was able to trigger ferroptosis in the adrenal gland pheochromocytoma cells. Arsenite significantly decreased the expressions of ferritin and NCOA4, but sharply enhanced the level of autophagy marker LC3B, suggesting the activation of ferritinophagy by arsenite. Inducer Up regulation . . Driver . A total of thirty-two healthy specificpathogenfree C57BL/6J male mice at seven weeks of age and weighted 20-24 g were purchased from the Experimental Animal Center of Chongqing Medical University. After administration of arsenite via drinking water, the animals were euthanized by pentobarbital sodium, three of the animals were subjected to the perfusion fixation, and subsequently, the hippocampus tissues were rapidly dissected on ice and immersed into 4% paraformaldehyde for pre-fixation. REF000358 ICD-11: 2C90 Adrenal gland pheochromocytoma CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00990 Ferroptosis-inducing erastin or cystine deprivation elevates MESH1 (HDDC3), whose overexpression depletes NADPH and sensitizes clear cell renal cell carcinoma cells to ferroptosis, whereas MESH1 depletion promotes ferroptosis survival by sustaining the levels of NADPH and GSH and by reducing lipid peroxidation. Inducer Up regulation . . Driver . . REF000183 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00121; CELL00057; CELL00195; CELL00005; CELL00021; CELL00051; CELL00095; CELL00062; CELL00120 RCC4; HEK-293T; H1975; MDA-MB-231; 786-O; PC3; HT1080; A673; PANC1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00398 Everolimus and RSL3/Erastin could synergistically inhibit the viability and induce ferroptosis in Renal cell carcinoma cells. Mechanistically, the inhibition of the mTOR-4EBP1 axis was found to be essential for the synergistic effects of Everolimus and RSL3/Erastin. Everolimus in combination with RSL3/Erastin is a promising therapeutic option for RCC treatment. Inducer Down regulation . . Suppressor . . REF000541 ICD-11: 2C90 Renal cell carcinoma CELL00155; CELL00081; CELL00004 ACHN; Caki-1; HEK-293 Ferroptosis (hsa04216); Glutathione metabolism (hsa00480); mTOR signaling pathway (hsa04150) Cell ferroptosis
unique00491 Rapamycin treatment inhibited MTOR signaling. And it is possible to induce ferroptosis in an hereditary leiomyomatosis and renal cell cancer (HLRCC) tumor model in vivo using a combination of rapamycin and Cyst(e)inase. Inducer Down regulation . . Suppressor . Ten million NCCFH1 cells suspended in a 1:1 ratio of PBS:Matrigel were injected into the right flank of each animal. Tumors were measured twice a week using a digital caliper, and tumor volumes were calculated according to the volume of an ellipsoid. When mean tumor volumes reached 100 mm3, an equal number of male and female mice were randomly assigned into four different groups. Thirty three of the 40 mice used in the experiment developed tumors. Thus, the final group assignment was as follow: vehicle (control group, n = 6, 3 female & 3 male), rapamycin (rapamycin only group, n = 7, 4 female & 3 male), Cyst(e)inase (Cyst(e)inase only group, n = 10, 5 female & 5 male), rapamycin+Cyst(e)inase (combination group, n = 10, 5 female & 5 male). Treatments were administered once every three days via intraperitoneal injection of either vehicle (Phosphate buffered saline containing 30% PEG300), rapamycin (0.6 mg/ml suspended in vehicle, injection dose = 0.6 mg per mouse), Cyst(e)inase (7.1 mg/ml suspended in vehicle, injection dose = 7.1 mg per mouse), and rapamycin+Cyst(e)inase combination (0.6 mg/ml rapamycin, 7.1 mg/ml Cyst(e)inase suspended in vehicle. REF000655 ICD-11: 2C90 Hereditary leiomyomatosis and renal cell cancer CELL00400; CELL10076 UOK262; NCCFH1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00399 Everolimus and RSL3/Erastin could synergistically inhibit the viability and induce ferroptosis in Renal cell carcinoma cells. Mechanistically, the inhibition of the mTOR-4EBP1 axis was found to be essential for the synergistic effects of Everolimus and RSL3/Erastin. Everolimus in combination with RSL3/Erastin is a promising therapeutic option for RCC treatment. Inducer Down regulation . . Suppressor . . REF000541 ICD-11: 2C90 Renal cell carcinoma CELL00155; CELL00081; CELL00004 ACHN; Caki-1; HEK-293 Ferroptosis (hsa04216); Glutathione metabolism (hsa00480); mTOR signaling pathway (hsa04150) Cell ferroptosis
unique01041 Artesunate (ART) significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant renal cell carcinoma (RCC) cells. P53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC. Inducer Up regulation . . Driver . . REF000256 ICD-11: 2C90 Renal cell carcinoma CELL00081; CELL00021; CELL00292; CELL00153 Caki-1; 786-O; KTCTL-26; A-498 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00485 Baicalin triggered ferroptosis in vitro and in vivo, as evidenced by ROS accumulation and intracellular chelate iron enrichment. Baicalin exerts its anticancer activity in bladder cancer by inducing FTH1-dependent ferroptosis, which will hopefully provide great therapeutic potential for bladder cancer treatment. Inducer . Down regulation . . Marker/Suppressor All mouse experiments were approved by the Use and Care of Animals Committee at Hangzhou Normal University. About 6 x 106 KU-19-19cells were injected into the about 3-5 weeks old female BALB/c nude mice (about 18 g,n = 5).Once palpable tumors appeared, the mice were randomized in four groups: the control (deionized water containing 7% Tween 80 and 0.1% CMC-Na) group, the DFO (100 mg/kg/day) group, the baicalin (200 mg/kg/day) group, and DFO + baicalin group. After 10 days of drug administration (intraperitoneal injection, once daily), mice were sacrificed, and tumor specimens resected were collected for immunohistochemical staining and Perl's staining (Solarbio Life Sciences, G1420). REF000644 ICD-11: 2C94 Bladder cancer CELL00067; CELL00027 5637; KU-19-19 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01719 PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation and induce ferroptosis of bladder cancer cells through the downregulation of GPX4. . . . Up regulation Suppressor Suppressor Twenty female BALB/c nude mice (4-6-weeks old, 15 g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). All mice were housed under specific pathogen-free conditions in 12/12 cycle of light at room temperature (24-26 ). Mice were fed a full fat diet and autoclaved water. The number of mice did not exceed five per cage. A total of 1 x 107 infected 5637 cells were suspended in 100 uL PBS and injected into the shoulder of the mice. Tumor length (L) and width (W) were observed for 4 weeks. Tumor volume (V) was monitored by measuring the length and width of the tumor using the following equation: V = (L x W2) x 0.5. The mice were euthanized by cervical dislocation after inhalational of CO2 when the maximum diameter of any tumor was near 1.5 cm. Tumor tissues were excised and embedded in paraffin for ematoxylin and eosin (HE) or IHC staining. REF000939 ICD-11: 2C94 Bladder cancer CELL00136; CELL00067; CELL00102; CELL00230 T24; 5637; J82; UM-UC3 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00165 Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j. Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc-/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. Compound 7j could be a promising lead for molecular-targeted anti- bladder cancer agents' discovery. Inducer . Down regulation . . Suppressor . REF000220 ICD-11: 2C94 Bladder cancer CELL00291; CELL00290; CELL00087; CELL00236; CELL00136; CELL00335 BEL-7402; MGC-803; HCT116; HCC827; T24; RT4 Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique00423 Fin56, a type 3 inducer, leads to ferroptosis mainly by promoting GPX4 degradation. Fin56 induces ferroptosis and autophagy in bladder cancer cells and that Fin56-triggered ferroptosis mechanistically depends on the autophagic machinery. Inducer . Down regulation . . Suppressor . REF000566 ICD-11: 2C94 Bladder cancer CELL00102; CELL00312; CELL00136; CELL00215; CELL10119 J82; 253J; T24; RT-112; MEF Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01594 CircST6GALNAC6 inhibits HSPB1 and promotes cell ferroptosis by occupying the phosphorylation site (Ser-15) of HSBP1 and activating the P38 MAPK signaling pathway. Therefore, enhancing the expression of circST6GALNAC6 to promote ferroptosis or using circST6GALNAC6 as a biomarker of ferroptosis sensitivity is of considerable importance to the development and application of ferroptosis intervention methods in bladder cancer. . . . Down regulation Driver Marker/Suppressor . REF000802 ICD-11: 2C94 Bladder cancer CELL00230; CELL00102 UM-UC-3; J82 Ferroptosis (hsa04216) Cell ferroptosis
unique00431 Erianin inhibited cell proliferation and triggered cell death in bladder cancer cells. Mechanistically, we showed NRF2 was a key determinant for erianin-triggered ferroptosis. NRF2 activation by TBHQ treatment protected against erianin-induced cell death and increased the expression of GPX4, ferritin, xCT and glutaminase. Inducer . Down regulation . . Marker/Suppressor 4-weeks-old female BALB/c nude mice aged were injected into 5 x 105 cells. Every 2 days mice weight and tumor size were assessed, and the tumor volume (V) was calculated with the formula: (maximum length) x (maximum width)2/2. Once tumors were found, the mice were stochastically divided into 2 groups: the control (PBS) group and the treatment (erianin 100 mg/kg) group. For 14 days, mice were injected intraperitoneally with drugs once a day, then puting the mice to death, after that tumors were taken for IHC (immunohistochemical) analysis. REF000581 ICD-11: 2C94 Bladder cancer CELL00335; CELL00366 RT4; KU-1919 Fatty acid metabolism (hsa01212); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique01192 circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. And circKIF4A-miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Therefore, targeting circKIF4A is very likely to be a potential method for treatment of papillary thyroid cancer in the future. . . . Up regulation Suppressor Suppressor KAT-5 and TPC-1 cells (2 x 107) were subcutaneously injected into nude mice (four mice/group, 4-week-old) and treated with intratumoral injection (50 uL si-circCON, si-circKIF4A) every four days. The volume of tumors was estimated every four days according to the formula 0.5 x width2 x length. After 28 days, the tumors were weighed. Forin vivolung metastasis assay, cells (1 x 105) were injected through tail veins (four mice/group). REF000437 ICD-11: 2D10 Thyroid cancer CELL00103; CELL00296 KAT-5; TPC-1 Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique00263 Vitamin C could significantly inhibit anaplastic thyroid cancer (ATC) cells growth through ferroptosis activation, evidenced by the GPX4 inactivation, ROS accumulation and iron-dependent lipid peroxidation. Inducer . Down regulation . . Suppressor . REF000356 ICD-11: 2D10 Anaplastic thyroid cancer CELL00152; CELL00468 8505C; C643 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy; Cell proliferation
unique01193 circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. And circKIF4A- miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Therefore, targeting circKIF4A is very likely to be a potential method for treatment of papillary thyroid cancer in the future. . . . Down regulation Driver Suppressor KAT-5 and TPC-1 cells (2 x 107) were subcutaneously injected into nude mice (four mice/group, 4-week-old) and treated with intratumoral injection (50 uL si-circCON, si-circKIF4A) every four days. The volume of tumors was estimated every four days according to the formula 0.5 x width2 x length. After 28 days, the tumors were weighed. Forin vivolung metastasis assay, cells (1 x 105) were injected through tail veins (four mice/group). REF000437 ICD-11: 2D10 Thyroid cancer CELL00103; CELL00296 KAT-5; TPC-1 Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique00730 Knockdown of HO-1 inhibits ferroptosis by upregulating the GPX4 expression in follicular thyroid cancer cells. We conclude that curcumin inhibits the tumorigenesis of follicular thyroid cancer via HO-1-induced activation of the ferroptosis signalling pathway. Inducer . Down regulation . . Suppressor . REF000950 ICD-11: 2D10 Follicular thyroid cancer CELL00251; CELL00251; CELL00411 Nthy-ori-3-1; Nthy-ori-3-1; FTC-238 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00729 Knockdown of HO-1 inhibits ferroptosis by upregulating the GPX4 expression in follicular thyroid cancer cells. We conclude that curcumin inhibits the tumorigenesis of follicular thyroid cancer via HO-1-induced activation of the ferroptosis signalling pathway. Inducer . Up regulation . . Driver . REF000950 ICD-11: 2D10 Follicular thyroid cancer CELL00251; CELL00251; CELL00411 Nthy-ori-3-1; Nthy-ori-3-1; FTC-238 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01755 SIRT6-driven sensitivity to ferroptosis via NCOA4-dependent autophagy and proposed ferroptosis inducers as promising therapeutic agents for anaplastic thyroid cancer patients. The clinically used ferroptosis inducer sulfasalazine showed promising therapeutic effects on SIRT6-upregulated thyroid cancer cells in vivo. . . . Up regulation Driver Driver Six-week-old male BALB/c-nu mice were provided by Beijing Vital River Laboratory Animal Technology Co. Ltd. All mice were randomly divided into 6 equal groups (CAL62-NC-Blank, CAL62-NC-sulfasalazine, CAL62-NC-sulfasalazine + CQ; CAL62-SIRT6-Blank, CAL62-SIRT6-sulfasalazine, CAL62-SIRT6-sulfasalazine + CQ). CAL62-NC or CAL62-SIRT6 cells (5 x 106) suspended in 100 ul PBS were injected subcutaneously into the axilla of each nude mouse. After 5 days, the mice were treated with different reagents: solvent (100 ul 0.1 M NaOH and 100 ul saline), sulfasalazine (200 mg/kg, i.p., dissolved in 100 ul 0.1 M NaOH), CQ (50 mg/kg, i.p., dissolved in 100 ul saline). REF000978 ICD-11: 2D10 Anaplastic thyroid cancer CELL00360; CELL00358 CAL62; BHT101 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01204 Circ_0067934 upregulated the expression of the ferroptosis-negative regulator SLC7A11 by sponging and inhibiting miR-545-3p in thyroid cancer cells. The overexpression of SLC7A11 or the inhibitor of miR-545-3p reversed circ_0067934 silencing-regulated thyroid cancer cell proliferation. . . . Up regulation Suppressor Suppressor BALB/c nude mice (18-20 g, 4-week-old, male) (n = 6) were purchased and applied for the tumor growth analysis of FTC133 cellsin vivo. About 1 x 106 FTC133 cells were transfected with control shRNA or circ_0067934 shRNA and were subcutaneously injected into the left fat pad of mice. After 5 days of injection, we measured tumor growth every 5 days. We sacrificed the mice after 30 days of injection. The tumor volume was calculated by (length x width2)/2. And the tumor weight was calculated at day 30. REF000459 ICD-11: 2D10 Thyroid cancer CELL00162; CELL00296 FTC133; TPC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01205 Circ_0067934 upregulated the expression of the ferroptosis-negative regulator SLC7A11 by sponging and inhibiting miR-545-3p in thyroid cancer cells. The overexpression of SLC7A11 or the inhibitor of miR-545-3p reversed circ_0067934 silencing-regulated thyroid cancer cell proliferation. . . . Down regulation Driver Suppressor BALB/c nude mice (18-20 g, 4-week-old, male) (n = 6) were purchased and applied for the tumor growth analysis of FTC133 cellsin vivo. About 1 x 106 FTC133 cells were transfected with control shRNA or circ_0067934 shRNA and were subcutaneously injected into the left fat pad of mice. After 5 days of injection, we measured tumor growth every 5 days. We sacrificed the mice after 30 days of injection. The tumor volume was calculated by (length x width2)/2. And the tumor weight was calculated at day 30. REF000459 ICD-11: 2D10 Thyroid cancer CELL00162; CELL00296 FTC133; TPC-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01558 Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. The expression of Ki67, PCNA, GPX4, and SLC7A11 was inhibited by si- CERS6-AS1 transfection. . . . Up regulation Suppressor Suppressor Animal experiments were approved by ethics committee of Wuzhou Red Cross Hospital. The TPC-1 cells transfected with sh-CERS6-AS1 or sh-NC were made into cell suspension (2 x 106/ml) with PBS. Then nude mice were randomly divided into sh-CERS6-AS1 group (n = 6) and sh-NC group (n = 6). The mice were subcutaneously inoculated with 200 ul corresponding cell suspension respectively, and then the weight and tumor volume of mice were recorded every other week. After 5 weeks, pentobarbital sodium (120 mg/kg) were intraperitoneally injected to make nude mice euthanasia, and then the tumors were stripped and weighed. Subsequently, immunohistochemistry and RT-PCR were performed. REF000768 ICD-11: 2D10 Papillary thyroid cancer CELL00251; CELL00422; CELL00074; CELL00297; CELL00296 Nthy-ori3-1; IHH-4; BCPAP; KTC-1; TPC-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01560 Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. The expression of Ki67, PCNA, GPX4, and SLC7A11 was inhibited by si-CERS6-AS1 transfection. . . . Up regulation Suppressor Suppressor Animal experiments were approved by ethics committee of Wuzhou Red Cross Hospital. The TPC-1 cells transfected with sh-CERS6-AS1 or sh-NC were made into cell suspension (2 x 106/ml) with PBS. Then nude mice were randomly divided into sh-CERS6-AS1 group (n = 6) and sh-NC group (n = 6). The mice were subcutaneously inoculated with 200 ul corresponding cell suspension respectively, and then the weight and tumor volume of mice were recorded every other week. After 5 weeks, pentobarbital sodium (120 mg/kg) were intraperitoneally injected to make nude mice euthanasia, and then the tumors were stripped and weighed. Subsequently, immunohistochemistry and RT-PCR were performed. REF000768 ICD-11: 2D10 Papillary thyroid cancer CELL00251; CELL00422; CELL00074; CELL00297; CELL00296 Nthy-ori3-1; IHH-4; BCPAP; KTC-1; TPC-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01559 Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. The expression of Ki67, PCNA, GPX4, and SLC7A11 was inhibited by si-CERS6-AS1 transfection. . . . Down regulation Driver Suppressor Animal experiments were approved by ethics committee of Wuzhou Red Cross Hospital. The TPC-1 cells transfected with sh-CERS6-AS1 or sh-NC were made into cell suspension (2 x 106/ml) with PBS. Then nude mice were randomly divided into sh-CERS6-AS1 group (n = 6) and sh-NC group (n = 6). The mice were subcutaneously inoculated with 200 ul corresponding cell suspension respectively, and then the weight and tumor volume of mice were recorded every other week. After 5 weeks, pentobarbital sodium (120 mg/kg) were intraperitoneally injected to make nude mice euthanasia, and then the tumors were stripped and weighed. Subsequently, immunohistochemistry and RT-PCR were performed. REF000768 ICD-11: 2D10 Papillary thyroid cancer CELL00251; CELL00422; CELL00074; CELL00297; CELL00296 Nthy-ori3-1; IHH-4; BCPAP; KTC-1; TPC-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01201 The downregulation of ETV4 repressed the tumor development through the low expression of SLC7A11, and the ETV4 overexpression obtained the contrary effects. Overall, knockdown of ETV4 suppressed the papillary thyroid cancer progression by promoting ferroptosis upon SLC7A11 downregulation. . . . Up regulation Suppressor Suppressor Six-week-old BALB/c female nude mice (HFK Bioscience, Beijing, China) were used to perform experimentsin vivo. One hundred forty-four mice were randomly divided into four groups (36 mice in each group). TPC-1 cells were stably transfected with NC shRNA or ETV4-shRNA, and GLAG-66 cells were stably transfected with ETV4-OE or Vector. 5 x 106 cells were injected subcutaneously into the right armpit in mice. After 7 days, the diameter of tumors was measured every 3 days to calculate the tumor volume. REF000457 ICD-11: 2D10 Papillary thyroid cancer CELL00296; CELL00422; CELL00251 TPC-1; IHH-4; Nthy-ori 3-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell cycle
unique00388 HDAC inhibitor Romidepsin converted SW13+ cells also had reduced mRNA expression of the mitochondrial ROS detoxifier superoxide dismutase 2 (SOD2), and the tumor suppressor p53. HDAC inhibitor treatment synergistically increased adrenocortical carcinoma cell death following induction of ferroptosis. Inducer Down regulation . . Suppressor . . REF000523 ICD-11: 2D11 Adrenocortical carcinoma CELL00130 SW13 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
dupunique00388 HDAC inhibitor Romidepsin converted SW13+ cells also had reduced mRNA expression of the mitochondrial ROS detoxifier superoxide dismutase 2 (SOD2), and the tumor suppressor p53. HDAC inhibitor treatment synergistically increased adrenocortical carcinoma cell death following induction of ferroptosis. Inducer Up regulation . . Driver . . REF000523 ICD-11: 2D11 Adrenocortical carcinoma CELL00130 SW13 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01175 Pediatric neuroblastoma (NB) cells harboring MYCN amplification are prone to undergo ferroptosis conferred by TFRC upregulation, suggesting that GPX4-targeting ferroptosis inducers or TFRC agonists can be potential strategies in treating MYCN-amplified NB. . . . Up regulation Driver Marker/Suppressor/Driver . REF000411 ICD-11: 2D50 Pediatric neuroblastoma CELL00344; CELL00221; CELL00042 SHEP; SK-N-AS; SY5Y Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00998 Inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. Increased IRP and TfR and decreased Fpn and FTH boosted up intracellular free iron, resulting in lipid peroxidation and ferroptosis in vitro and in vivo. . . . Up regulation Suppressor Marker/Suppressor Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice. REF000199 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00293; CELL10070; CELL00519; CELL10071 AMC-HN3; HN3R; HN4; HN4R Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00143 The suppression of GLRX5 activated the IRE-binding activity of IRP and canonical iron-starvation responsive proteins (increased TfR, decreased FTH), resulting in increased intracellular free iron. The data suggest that inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. . . . Up regulation Suppressor Marker/Suppressor Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice. REF000199 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00293; CELL10070; CELL00519; CELL10071 AMC-HN3; HN3R; HN4; HN4R Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01333 Overexpression of CAV1 in head and neck squamous cell carcinoma (HNSCC) inhibited the process of ferroptosis, leading to aggressive phenotypes, as well as worse prognosis. And the knockdown of CAV1 could reduce the expression of GPX4. . . . Up regulation Suppressor Suppressor . REF000602 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00493; CELL00461; CELL00159; CELL00219; CELL00218 HN6; HN30; CAL27; SCC9; SCC25 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00999 Inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. Increased IRP and TfR and decreased Fpn and FTH boosted up intracellular free iron, resulting in lipid peroxidation and ferroptosis in vitro and in vivo. . . . Up regulation Suppressor Marker/Suppressor Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice. REF000199 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00293; CELL10070; CELL00519; CELL10071 AMC-HN3; HN3R; HN4; HN4R Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01322 GRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells. PGRMC1 expression increased FAO and ferroptosis sensitivity from in vivo mice experiments. And PGRMC1 promotes ferroptosis by xCT (SLC7A11) inhibition in head and neck cancer (HNC) cells. . . . Down regulation Driver Suppressor Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN4 cells with transfection of PGRMC1 overexpression or control vector and HN4PCC with shPGRMC1 or control vector were subcutaneously injected into the bilateral flank of nude mice. When gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). REF000575 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00491; CELL00519 HN3; HN4 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01341 The study demonstrate the critical role of IL-6-induced ferroptosis resistance during head and neck squamous cell carcinoma carcinogenesis. The IL-6/STAT3/xCT (encoded by SLC7A11) axis acts as a novel mechanism driving tumor progression and thus may potentially be utilized as a target for tumor prevention and therapy. . . . Up regulation Suppressor Suppressor Four-week-old male BALB/c-nu mice were purchased from the Shanghai Laboratory Animal Center (Shanghai, China). About 4 x 106 CAL27 cells were stably transfected with lentivirus. After administration of 2 ug/mL puromycin for three days, transfection efficiency was confirmed by western blotting. Approximately 2 x 106 transfected cells were subcutaneously injected into flanks. For the drug-administration study, 20 mg/kg erastin (S7242, Selleck Chemicals) were administrated intraperitoneally twice every other day. Approximately 20 uL IL-6 (10 ug/mL, PeproTech, USA) were given intratumorally twice every other day. REF000607 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00519; CELL00159 HN4; CAL27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ferroptosis (hsa04216); JAK-STAT signaling pathway (hsa04630) Cell ferroptosis; Cell proliferation
unique01342 The study demonstrate the critical role of IL-6-induced ferroptosis resistance during head and neck squamous cell carcinoma carcinogenesis. The IL-6/ STAT3/xCT (encoded by SLC7A11) axis acts as a novel mechanism driving tumor progression and thus may potentially be utilized as a target for tumor prevention and therapy. . . . Up regulation Suppressor Suppressor Four-week-old male BALB/c-nu mice were purchased from the Shanghai Laboratory Animal Center (Shanghai, China). About 4 x 106 CAL27 cells were stably transfected with lentivirus. After administration of 2 ug/mL puromycin for three days, transfection efficiency was confirmed by western blotting. Approximately 2 x 106 transfected cells were subcutaneously injected into flanks. For the drug-administration study, 20 mg/kg erastin (S7242, Selleck Chemicals) were administrated intraperitoneally twice every other day. Approximately 20 uL IL-6 (10 ug/mL, PeproTech, USA) were given intratumorally twice every other day. REF000607 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00519; CELL00159 HN4; CAL27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ferroptosis (hsa04216); JAK-STAT signaling pathway (hsa04630) Cell ferroptosis; Cell proliferation
unique00142 The suppression of GLRX5 activated the IRE-binding activity of IRP and canonical iron-starvation responsive proteins (increased TfR, decreased FTH), resulting in increased intracellular free iron. The data suggest that inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. . . . Down regulation Suppressor Marker/Suppressor/Driver Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice. REF000199 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00293; CELL10070; CELL00519; CELL10071 AMC-HN3; HN3R; HN4; HN4R Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00175 Histone deacetylase SIRT1 gene silencing or pharmacological inhibition by EX-527 suppressed EMT and consequently decreased ferroptosis, whereas SIRT inducers, resveratrol and SRT1720, increased ferroptosis. In head and neck cancer (HNC) cells with low expression of E-cadherin, the treatment of 5-azacitidine diminished the hypermethylation of CDH1, resulting in increased E-cadherin expression and decreased ferroptosis susceptibility. Suppressor Up regulation . . Suppressor . Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN9 cells with transfection of CDH1 or control vector or HN4 cells with ZEB1 or control vector were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). Each group included six mice. REF000229 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00293; CELL00519; CELL00492; CELL00493; CELL00494; CELL00490 AMC HN3; HN4; HN5; HN6; HN9; HN10 Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis
unique00174 Histone deacetylase SIRT1 gene silencing or pharmacological inhibition by EX-527 suppressed EMT and consequently decreased ferroptosis, whereas SIRT inducers, resveratrol and SRT1720, increased ferroptosis. In head and neck cancer (HNC) cells with low expression of E-cadherin, the treatment of 5-azacitidine diminished the hypermethylation of CDH1, resulting in increased E-cadherin expression and decreased ferroptosis susceptibility. Suppressor Down regulation . . Driver . Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN9 cells with transfection of CDH1 or control vector or HN4 cells with ZEB1 or control vector were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). Each group included six mice. REF000229 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00293; CELL00519; CELL00492; CELL00493; CELL00494; CELL00490 AMC HN3; HN4; HN5; HN6; HN9; HN10 Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis
unique00173 Histone deacetylase SIRT1 gene silencing or pharmacological inhibition by EX-527 suppressed EMT and consequently decreased ferroptosis, whereas SIRT inducers, resveratrol and SRT1720, increased ferroptosis. In head and neck cancer (HNC) cells with low expression of E-cadherin, the treatment of 5-azacitidine diminished the hypermethylation of CDH1, resulting in increased E-cadherin expression and decreased ferroptosis susceptibility. Inducer Up regulation . . Driver . Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN9 cells with transfection of CDH1 or control vector or HN4 cells with ZEB1 or control vector were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). Each group included six mice. REF000229 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00293; CELL00519; CELL00492; CELL00493; CELL00494; CELL00490 AMC HN3; HN4; HN5; HN6; HN9; HN10 Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis
unique00018 Sulfasalazine-resistant head and neck squamous cell carcinoma (HNSCC) cells were found to highly express ALDH3A1 and knockdown of ALDH3A1 rendered these cells sensitive to sulfasalazine. The combination of dyclonine and sulfasalazine cooperatively suppressed the growth of highly ALDH3A1-expressing HNSCC or gastric tumors that were resistant to sulfasalazine monotherapy. Inducer Down regulation . . Suppressor . HSC-2 or K19-Wnt1/C2mE-KP cells (2 x 106 cells per site) were implanted subcutaneously in the flank of athymic nude mice (CLEA Japan) or C57BL6 mice (CLEA Japan), respectively. The mice were then injected intraperitoneally with physiological saline or sulfasalazine (350 mg/kg per day), or with combinations of physiological saline, sulfasalazine (400 mg/kg per day), and dyclonine hydrochloride (5 mg/kg per day). REF000051 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00428; CELL00176; CELL00177; CELL00178; CELL00218; CELL00538; CELL00087; CELL00540 OSC19; HSC-2; HSC-3; HSC-4; SCC25; DMS114; HCT116; 4T1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01144 Knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. Importantly, silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2. . . . Down regulation Driver Suppressor . REF000379 ICD-11: 2E81 Hemangioma CELL10072 HemECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Notch signaling pathway (hsa04330) Cell ferroptosis; Cell proliferation
unique01145 Knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/ NOTCH2 axis. Importantly, silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2. . . . Up regulation Suppressor Suppressor . REF000379 ICD-11: 2E81 Hemangioma CELL10072 HemECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Notch signaling pathway (hsa04330) Cell ferroptosis; Cell proliferation
unique01143 Knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. Importantly, silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2. . . . Up regulation Suppressor Suppressor . REF000379 ICD-11: 2E81 Hemangioma CELL10072 HemECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Notch signaling pathway (hsa04330) Cell ferroptosis; Cell proliferation
unique01660 Lnc-TC/miR-142-5p/CUL4B signaling axis promoted cell ferroptosis to participate in benzene hematotoxicity, and was a potential biomarker for risk screening and health surveillance of benzene-exposed workers. The expression of GPX4 was negatively correlated with both Lnc-TC and CUL4B. . . . Down regulation Driver Suppressor . REF000867 ICD-11: 3A70 Benzene hematotoxicity CELL00266 AHH-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01661 Lnc-TC/ miR-142-5p/CUL4B signaling axis promoted cell ferroptosis to participate in benzene hematotoxicity, and was a potential biomarker for risk screening and health surveillance of benzene-exposed workers. The expression of GPX4 was negatively correlated with both Lnc-TC and CUL4B. . . . Up regulation Suppressor Suppressor . REF000867 ICD-11: 3A70 Benzene hematotoxicity CELL00266 AHH-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01662 Lnc-TC/miR-142-5p/ CUL4B signaling axis promoted cell ferroptosis to participate in benzene hematotoxicity, and was a potential biomarker for risk screening and health surveillance of benzene-exposed workers. The expression of GPX4 was negatively correlated with both Lnc-TC and CUL4B. . . . Down regulation Driver Suppressor . REF000867 ICD-11: 3A70 Benzene hematotoxicity CELL00266 AHH-1 Ferroptosis (hsa04216) Cell ferroptosis
unique01655 The iron-regulatory system IRP1, ferroptosis regulator DHODH, and fatty acids metabolism rate-limiting enzyme ALOX12 were the crucial influencers in regulating ferroptosis, this provides the potential target in attenuating benzene-induced anemia of inflammation. . . . Down regulation Suppressor Driver 4-week male C57BL/6J mice (20-22 g) were obtained from the vital river and preconditioned for one week. Mice were divided into two groups, either exposed to benzene or fresh air in the exposure system for 6 h/day, 6 days/week, for two months. In the last exposure day, the mice were fast for 10 h. Subsequently, the mice were injected with tribromoethanol (T48402, Sigma, USA) (300 mg/kg). REF000862 ICD-11: 3A9Z Anemia CELL00266 AHH-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00146 High-dose auranofin (AUR) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity.In conclusion, TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders. Inducer Down regulation . . Suppressor . C57BL/6J mice (7-8 weeks of age, both males and females) were purchased from Vital River Laboratory Animal Technology Co., Ltd., Beijing, China. Hfe-/-mice were kindly provided by Dr. Nancy C. Andrews. All mice were housed in a specific pathogen-free facility and fed an egg white-based AIN-76A diet containing 50 mg/kg iron (Research Diets, Inc., New Brunswick, NJ). REF000204 ICD-11: 3B10-3B11 Hemochromatosis CELL00012; CELL00057 Huh7; HEK293T JAK-STAT signaling pathway (hsa04630); NF-kappa B signaling pathway (hsa04064); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00147 High-dose auranofin (AUR) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity.In conclusion, TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders. Inducer Down regulation . . Suppressor . C57BL/6J mice (7-8 weeks of age, both males and females) were purchased from Vital River Laboratory Animal Technology Co., Ltd., Beijing, China. Hfe-/-mice were kindly provided by Dr. Nancy C. Andrews. All mice were housed in a specific pathogen-free facility and fed an egg white-based AIN-76A diet containing 50 mg/kg iron (Research Diets, Inc., New Brunswick, NJ). REF000204 ICD-11: 3B10-3B11 Hemochromatosis CELL00012; CELL00057 Huh7; HEK293T JAK-STAT signaling pathway (hsa04630); NF-kappa B signaling pathway (hsa04064); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00145 High-dose auranofin (AUR) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity.In conclusion, TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders. Inducer Down regulation . . Suppressor . C57BL/6J mice (7-8 weeks of age, both males and females) were purchased from Vital River Laboratory Animal Technology Co., Ltd., Beijing, China. Hfe-/-mice were kindly provided by Dr. Nancy C. Andrews. All mice were housed in a specific pathogen-free facility and fed an egg white-based AIN-76A diet containing 50 mg/kg iron (Research Diets, Inc., New Brunswick, NJ). REF000204 ICD-11: 3B10-3B11 Hemochromatosis CELL00012; CELL00057 Huh7; HEK293T JAK-STAT signaling pathway (hsa04630); NF-kappa B signaling pathway (hsa04064); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01229 IFN- ( IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01227 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01219 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01223 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01220 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01225 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01217 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01226 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01228 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01222 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01218 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01221 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01224 IFN- (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21) and SLE IgG suppresses the transcription of GPX4 by promoting binding of CREM to the Gpx4 promoter. Together, neutrophil ferroptosis is an important driver of neutropenia in systemic lupus erythematosus (SLE) and heavily contributes to disease manifestations. . . . Down regulation Driver Suppressor In ferroptosis rescue experiments, LPX-1 (10 mg/kg), CTX (20 mg/kg) or 0.1 ml DMSO (10%) was administered intraperitoneally to female MRL/Mpj and MRL/lpr mice every other day for six weeks beginning at 12 weeks of age. Urine was collected in the morning once a week. Mice were sacrificed at 18 weeks of age, and spleen, kidneys, lymph nodes, and peripheral blood were collected for analysis. For in vivo treatment, MRL/lprmice were administered 0.1 ml DMSO (10%), Cl-amidine (20 mg/kg), LPX-1 (10 mg/kg), or Cl-amidine (20 mg/kg) combined with LPX-1 (10 mg/kg) intraperitoneally every other day for 3 weeks starting at 12 weeks of age. REF000477 ICD-11: 4A40 Systemic lupus erythematosus CELL10094 Peripheral blood mononuclear cells (PBMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01672 Berberine (BBR) stimulated GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet cells in diabetes mellitus, which functioned similarly as ferroptosis inhibitor Fer-1. Suppressor . Up regulation . . Suppressor . REF000883 ICD-11: 5A10 Diabetes mellitus . isletcells Ferroptosis (hsa04216) Cell ferroptosis
unique00692 Empagliflozin, a clinical hypoglycemic gliflozin drug, can inhibit ferroptosis and enhance skeletal muscle cell survival and paracrine function under hyperglycemic condition via restoring the expression of GPX4. This study highlights the potential of intramuscular injection of empagliflozin for treating diabetic hindlimb ischemia. Suppressor . Up regulation . . Suppressor For diabetes induction, C57BL/6 mice were fed with high fat diet (HFD) for 3 weeks (20% kcal protein, 20% kcal carbohydrate, and 60% kcal fat). Intraperitoneal administration of 60 mg/kg body weight streptozotocin (STZ, Sigma-Aldrich, St Louis, MO, USA) diluted in sodium citrate buffer was then performed for the following six days. Mice were fasted overnight prior to each STZ injection and blood glucose level measurement. Blood glucose level was evaluated using Accu-Check Integra (Roche Diagnostics, Shanghai, China). Mice with blood glucose level above 16.6 mM were assumed as diabetic mice, and were used for establishing diabetic HLI model as described previously. REF000917 ICD-11: 5A10-5A11 Diabetic hindlimb ischemia CELL00546; CELL10037; CELL00353; CELL00057 C2C12; HUVECs; MOVAS; HEK293T Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00723 Salidroside/GPX4-mediated ferroptosis inhibition is crucial for promoting angiogenesis and blood perfusion recovery in diabetic hindlimb ischemia mice. Suppressor . Up regulation . . Suppressor For diabetes induction, C57BL/6 mice were given a high-fat diet for three weeks that contained 20% protein, 20% carbohydrate, and 60% fat. Sodium citratebuffer-diluted 60 mg/kg body weight streptozotocin (STZ; Sigma-Aldrich, St. Louis, MO) were administered intraperitoneally for the next constitutive six days. Prior to each STZ injection and blood glucose testusing Accu-Check Integra (Roche Diagnostics, Shanghai, China), mice were fasted overnight. Mice with blood glucose levels higher than 16.6 mM were considered diabetic and were utilized to establish the diabetic HLI model. REF000941 ICD-11: 5A10-5A11 Diabetic hindlimb ischemia CELL00546; CELL10037; CELL00353 MyoblastC2C12; HUVECs; MOVAS Ferroptosis (hsa04216) Cell ferroptosis
unique00140 Cryptochlorogenic acid (CCA) functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. System xc- which is composed of SLC7A11 and SLC3A2, served as the provider of GSH synthesis. Suppressor . Down regulation . . Driver Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful. REF000195 ICD-11: 5A10 Diabetes mellitus CELL00602 INS-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00141 Bilirubin protects transplanted islets by inhibiting ferroptosis through multiple mechanisms, including ROS scavenging ability, iron-chelating property, and upregulation of Nrf2/HO-1 signaling pathway. Bilirubin could improve islet viability and function through inhibiting ferroptosis, which could be of clinic interest to apply bilirubin into the islet transplantation system. Islet transplantation is an attractive treatment for type 1 diabetic patients. Suppressor . Up regulation . . Marker/Suppressor BALB/c mouse are used as recipients and donors in the transplantation. Fifteen diabetic BALB/c mice were randomly divided into 5 groups (3 mice in each group). Then, 250 IEQ islets pretreated with or without bilirubin (20 uM) for 48 h were transplanted into the subrenal site of the diabetic mouse. Ferrin 1 (10 uM) and DFO (10 mM) pretreated islets were also transplanted for comparison. Following, the non-fasting glucose level and bodyweight was the mice were recorded daily. REF000196 ICD-11: 5A10 Diabetes mellitus CELL00551 Min6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00139 Cryptochlorogenic acid (CCA) functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. System xc- which is composed of SLC7A11 and SLC3A2, served as the provider of GSH synthesis. Suppressor . Up regulation . . Suppressor Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful. REF000195 ICD-11: 5A10 Diabetes mellitus CELL00602 INS-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00138 Cryptochlorogenic acid (CCA) functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. System xc- which is composed of SLC7A11 and SLC3A2, served as the provider of GSH synthesis. Suppressor . Up regulation . . Suppressor Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful. REF000195 ICD-11: 5A10 Diabetes mellitus CELL00602 INS-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00444 Acrolein is a typical food and environmental pollutant and a risk factor for diabetes. Resveratrol, an antioxidant natural product, may relieve ER stress and upregulate PPAR expression, thereby inhibiting acrolein-induced ferroptosis. Inducer Down regulation . . Suppressor . . REF000590 ICD-11: 5A10 Diabetes mellitus CELL00551 MIN6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique00443 Acrolein is a typical food and environmental pollutant and a risk factor for diabetes. Resveratrol, an antioxidant natural product, may relieve ER stress and upregulate PPAR expression, thereby inhibiting acrolein-induced ferroptosis. Suppressor Up regulation . . Suppressor . . REF000590 ICD-11: 5A10 Diabetes mellitus CELL00551 MIN6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique01724 NEDD4L facilitates GC ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of polycystic ovary syndrome. . . . Down regulation Driver Suppressor Adult female C57BL/6J mice were purchased from Cyagen Bioscience (Santa Clara, CA, USA). Prior to the experiment, the animals were allowed to adapt to the environment for 1 week. For this study, all procedures were approved by the Ethics Committee of Shanghai Seventh Peoples Hospital (item number: 2021-AR-059). Adult female C57BL/6J mice were housed withaccess to food and waterad libitum. The PCOS mouse model was established as described previously. In brief, female C57BL/6J mice (4 weeks old) were subcutaneously injected with DHEA (6 mg/0.1kg body weight) daily for 20 days. REF000945 ICD-11: 5A80.1 Polycystic ovary syndrome CELL00106 KGN Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00738 Morphological results showed that after metformin treatment, polycystic lesions in ovaries were reduced, the ovarian function was restored, and the expressions of SIRT3 and GPX4 were elevated. Metformin could regulate ferroptosis to improve polycystic ovary syndrome via the SIRT3/AMPK/mTOR pathway. Suppressor . Up regulation . . Suppressor n = 6 blank control group was created. The mice in the control group were fed regular food and gavaged with normal saline daily. The mice in the control group were given a high-fat diet and 1 mg/kg of letrozole via gavage for 21 days to establish a PCOS model of insulin resistance and hyperandrogenism. The mice, after successful modeling, were randomly divided into PCOS group and metformin group (n = 6). During the treatment period, the control group continued to be fed with normal feed and given normal saline; the PCOS group was fed with continuous high-fat feed and given letrozole (1 mg/kg/day) by intragastric administration, and the metformin group was given metformin by intragastric administration (200 mg/kg/day). After 30 days of treatment, the experimental mice were euthanized, serum was collected, one mouse ovary was collected for histological examination, and the other was stored in a -80 refrigerator for molecular biology experimental research. REF000961 ICD-11: 5A80.1 Polycystic ovary syndrome . . Ferroptosis (hsa04216) Cell ferroptosis
unique01671 The overexpression of miR-93-5p can promote apoptosis by reducing the expression of Bcl2 and increasing ferroptosis by downregulating GPX4, SLC7A11 and Nrf2 expression in the KGN cell line. miR-93-5p promotes the apoptosis and ferroptosis in GC by regulating the NF-kB signaling pathway. Our study identified miR-93-5p as a new molecular target for improving the function of GCs in polycystic ovary syndrome patients. . . . Down regulation Driver Suppressor C57BL/6 J (3-week-old) female mice, weighing 15-20 g, were purchased from Beijing Vitalriver Laboratory Animal Technology Co Ltd., China. Experimental animals were randomly divided into control (glycerol treatment) and experimental groups (PCOS, DHEA treatment). The modeling method was as described previously. The PCOS model and control was verified successfully as our previous results, and ovarian tissue was extracted for RT-qPCR detection. REF000881 ICD-11: 5A80.1 Polycystic ovary syndrome CELL00106 KGN Fatty acid metabolism (hsa01212); NF-kappa B signaling pathway (hsa04064); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01253 circRHBG inhibits ferroptosis in Polycystic ovary syndrome cells through the circRHBG/miR-515-5p/SLC7A11 axis in PCOS, which may provide new diagnostic molecular markers and therapeutic targets for PCOS. . . . Up regulation Suppressor Suppressor We recruited 12 infertility patients (6 PCOS and 6 controls) aged 20 and 38 who underwent in vitro fertilization (IVF) at the Department of Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-Sen University. All patients were treated the antagonist stimulation protocol. Briefly, on cycle day 2, ovarian stimulation was started by daily injection of recombinant FSH (r-FSH) (Gonal-F; Merck Serono). Gonadotropin-releasing hormone (GnRH) antagonist (Cetrotide, 0.25 mg; Merck Serono) injection was started from the day 6 of stimulation. When at least three follicles had reached 17 mm or two follicles had reached 18 mm in diameter, an intramuscular injection of 5,000 IU-10000 IU of human chorionic gonadotropin (hCG) is used for triggering final oocyte maturation. REF000503 ICD-11: 5A80.1 Polycystic ovary syndrome CELL00106; CELL00324 KGN; SVOG Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01254 circRHBG inhibits ferroptosis in Polycystic ovary syndrome cells through the circRHBG/ miR-515-5p/SLC7A11 axis in PCOS, which may provide new diagnostic molecular markers and therapeutic targets for PCOS. . . . Down regulation Driver Suppressor We recruited 12 infertility patients (6 PCOS and 6 controls) aged 20 and 38 who underwent in vitro fertilization (IVF) at the Department of Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-Sen University. All patients were treated the antagonist stimulation protocol. Briefly, on cycle day 2, ovarian stimulation was started by daily injection of recombinant FSH (r-FSH) (Gonal-F; Merck Serono). Gonadotropin-releasing hormone (GnRH) antagonist (Cetrotide, 0.25 mg; Merck Serono) injection was started from the day 6 of stimulation. When at least three follicles had reached 17 mm or two follicles had reached 18 mm in diameter, an intramuscular injection of 5,000 IU-10000 IU of human chorionic gonadotropin (hCG) is used for triggering final oocyte maturation. REF000503 ICD-11: 5A80.1 Polycystic ovary syndrome CELL00106; CELL00324 KGN; SVOG Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00454 Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical polycystic ovary syndrome (PCOS)-like rat model. N-acetylcysteine treatment results in increased mRNA expression of Aifm2, a negative regulator of GPX4-independent ferroptosis in the placenta. Moreover, NAC reverses HAIR-induced uterine and placental ferroptosis through activation of the Slc7a11/GSH/GPX4 axis. Suppressor . Up regulation . . Suppressor Adult Sprague-Dawley rats (70 days old) of both sexes were purchased from the Laboratory Animal Centre of Harbin Medical University, Harbin, China. Before the experiment, female rats were allowed to acclimatize for a minimum of 1 week and then were monitored daily by vaginal lavage to determine the stage of the estrous cycle as previously described (Zhanget al., 2016). Pregnancy was achieved by housing female rats on the night of proestrus with fertile males of the same strain at a 2:1 ratio. Confirmation of mating was performed the morning after by the presence of a vaginal plug, and this was considered as GD 0.5. The rats were sacrificed between 8:00 a.m. and 9:00 a.m. hours on GD 14.5. REF000596 ICD-11: 5A80.1 Polycystic ovary syndrome CELL10095 Uterine and placental tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell differentiation
unique00453 Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical polycystic ovary syndrome (PCOS)-like rat model. N-acetylcysteine treatment results in increased mRNA expression of Aifm2, a negative regulator of GPX4-independent ferroptosis in the placenta. Moreover, NAC reverses HAIR-induced uterine and placental ferroptosis through activation of the Slc7a11/GSH/GPX4 axis. Suppressor . Up regulation . . Suppressor Adult Sprague-Dawley rats (70 days old) of both sexes were purchased from the Laboratory Animal Centre of Harbin Medical University, Harbin, China. Before the experiment, female rats were allowed to acclimatize for a minimum of 1 week and then were monitored daily by vaginal lavage to determine the stage of the estrous cycle as previously described (Zhanget al., 2016). Pregnancy was achieved by housing female rats on the night of proestrus with fertile males of the same strain at a 2:1 ratio. Confirmation of mating was performed the morning after by the presence of a vaginal plug, and this was considered as GD 0.5. The rats were sacrificed between 8:00 a.m. and 9:00 a.m. hours on GD 14.5. REF000596 ICD-11: 5A80.1 Polycystic ovary syndrome CELL10095; CELL10095 Uterine and placental tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell differentiation
unique00737 Morphological results showed that after metformin treatment, polycystic lesions in ovaries were reduced, the ovarian function was restored, and the expressions of SIRT3 and GPX4 were elevated. Metformin could regulate ferroptosis to improve polycystic ovary syndrome (PCOS) via the SIRT3/AMPK/mTOR pathway. Suppressor Up regulation . . Suppressor . n = 6 blank control group was created. The mice in the control group were fed regular food and gavaged with normal saline daily. The mice in the control group were given a high-fat diet and 1 mg/kg of letrozole via gavage for 21 days to establish a PCOS model of insulin resistance and hyperandrogenism. The mice, after successful modeling, were randomly divided into PCOS group and metformin group (n = 6). During the treatment period, the control group continued to be fed with normal feed and given normal saline; the PCOS group was fed with continuous high-fat feed and given letrozole (1 mg/kg/day) by intragastric administration, and the metformin group was given metformin by intragastric administration (200 mg/kg/day). After 30 days of treatment, the experimental mice were euthanized, serum was collected, one mouse ovary was collected for histological examination, and the other was stored in a -80 refrigerator for molecular biology experimental research. REF000961 ICD-11: 5A80.1 Polycystic ovary syndrome . . Ferroptosis (hsa04216) Cell ferroptosis
unique00393 Cadmium induced ferroptosis by iron homeostasis dysregulation, mediated by excessive activation of HMOX-1. The disruption of autophagy flow contributed to Cd-induced testicular dysfunction and attenuated testosterone synthesis. Inducer . Up regulation . . Driver Eight-week-old adult male C57BL/6J mice were raised for 7 days before the study in a temperature and humidity controlled animal facility (22-25 , 50% relative humidity) with a12-h light/dark cycles. A total of 10 mice were randomly assigned into two groups. As described in our previous study, the control group was treated with 0.9% NaCl (0 mg CdCl2), and the treatment group was intraperitoneally injected with CdCl2 at a dose of 1.0 mg per kg of body weight for 1 week. REF000529 ICD-11: 5A81 Testicular dysfunction CELL00558 TM3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00638 Atorvastatin decreased the level of GPX4 and depleted GGPP production, but not Fer-1. Atorvastatin was able to induce ferroptosis in adipose tissue, which was due to increased ROS and an increase in cellular senescence. Moreover, this effect could be reversed by the supplement of GGPP. Taken together, our results suggest that the induction of ferroptosis contributed to statin-induced cell senescence in adipose tissue and may contributed to obesity disease. Inducer . Down regulation . . Suppressor Mice were sacrificed by cervical dislocation. As described previously, epidydimal adipose tissues (EAT) were isolated and minced into ~5-mg pieces in DMEM containing 10% FBS. After 2 h of incubation, 50 mg of small pieces were placed in serum-free DMEM and exposed to 1 umol/L atorvastatin for 18 h, and 0.1% DMSO served as a control. In specific experiments, EAT explants were also treated with GGPP (50 uM; GlpBio), or ferrostatin-1 (Fer-1, 8 uM), and added to the culture medium at the same time as was atorvastatin. Group animal size was n = 6-8 per group. The exact group size is specially described in the Figure legends. REF000873 ICD-11: 5B81 Obesity . Adipose tissue Ferroptosis (hsa04216) Cell ferroptosis; Cell senescence
unique00932 Mutations of LAMP2 cause the classic triad of myopathy, cardiomyopathy and encephalopathy of Danon disease (DD). LAMP2-KD reduced the concentration of cytosolic cysteine, resulting in low glutathione (GSH), inferior antioxidant capability and mitochondrial lipid peroxidation. ROS induced RPE cell death through ferroptosis. Inhibition of glutathione peroxidase 4 (GPx4) increased lethality in LAMP2-KD cells compared to controls. . . . Up regulation Suppressor Marker/Suppressor . REF000103 ICD-11: 5C51 Danon disease CELL00072; CELL10099 ARPE-19; HfRPE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01251 FGF21 could protect hepatocytes from developing iron overload-induced ferroptosis by stimulating HO-1 ubiquitination and subsequent degradation. The FGF21HO-1 pathway could be targeted for treating iron overload-induced ferroptosis-related diseases, particularly hereditary haemochromatosis (HH). . . . Down regulation Suppressor Driver/Suppressor In the adenovirus-mediated FGF21 over-expression mouse model, 12-week-old C57BL/6J male mice were divided into four groups: (1) EGFP vector overexpression + PBS injection group (n = 10), (2) EGFP vector overexpression + iron dextran injection group (n = 10), (3) FGF21-EGFP overexpression + PBS injection group (n = 10) and (4) FGF21-EGFP overexpression + iron dextran injection group (n = 10). The mice were administered PBS and iron dextran by intraperitoneal injection for 7 days. REF000501 ICD-11: 5C64 Hereditary haemochromatosis CELL10142 Hepatocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00365 Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function. Suppressor . Down regulation . . Driver Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups. REF000493 ICD-11: 6D71 Diabetes-induced cognitive dysfunction CELL10125 hippocampal neurons Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00364 Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function. Suppressor . Up regulation . . Suppressor Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups. REF000493 ICD-11: 6D71 Diabetes-induced cognitive dysfunction CELL10125 hippocampal neurons Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00627 Gastrodin (GAS) inhibited ferroptosis in hippocampal neurons by activating the Nrf2/Keap1-GPx4 signaling pathway, suggesting its possible application as a functional food for improving vascular dementia by inhibiting ferroptosis. Suppressor . Up regulation . . Suppressor Male Sprague-Dawley rats (weight 260 ± 20 g; Guizhou Medical University Experimental Animal Center; Certificate No. SCXK2018-0001; Grant No. 2200483) were reared in a specific pathogen-free environment with 12 h light/dark cycle and 55% ± 10% humidity at a temperature of 20~25 , were provided with sufficient feed and sterile drinking water and fasted for 6 h before and after surgery. All animal experiments were performed in accordance with the Declaration of Helsinki and the Guide for the Care and Use of Laboratory Animals. REF000860 ICD-11: 6D81 Vascular dementia CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00150 6-hydroxydopamine (6-OHDA) treatment-induced ferroptosis in SH-SY5Y cells mainly by disturbing the protein expression of GPX4 and ACSL4. Collectively, the activation of the p62-Keap1-Nrf2 pathway prevents 6-OHDA-induced ferroptosis in SH-SY5Y cells, targeting this pathway in combination with a pharmacological inhibitor of ferroptosis can be a potential approach for parkinson's disease therapy. Inducer . Up regulation . . Driver The AB strain of wild-type zebrafish (Danio rerio) was applied in this study. Zebrafish larvae at 4 dpf (days post-fertilization) were co-incubated with 250 uM 6-OHDA or 1.5 ug/mL nomifensine (Nomi, a dopamine transporter inhibitor) in 6-well plates at a density of 30 zebrafish embryos per group for 2 days and the medium was refreshed every day. The swimming total distance of each fish was recorded for 10 min and was analyzed by an automated video tracking system. REF000206 ICD-11: 8A00 Parkinson disease CELL00042 SH-SY5Y Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00673 L. lactis MG1363-pMG36e-GLP-1 exerts neurotrophic effects via activating the Keap1/Nrf2/GPX4 signalling pathway to down-regulate ACSL4 and up-regulate FSP1 to suppress ferroptosis. These results indicated that the neurotrophic effects of the next-generation probiotics L. lactis MG1363-pMG36e-GLP-1 against MPTP-induced Parkinsonism are mediated by modulating oxidative stress, inhibiting ferroptosis, and redressing dysbiosis. Suppressor . Down regulation . . Driver Fifty male C57BL/6 mice provided by Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China) resided in an animal house (temperature 26 ± 1 , humidity 50 ± 10%), in which the light was on for 12 h and off for 12 h. Mice were acclimatised for 1 week and allowed water and animal food with no limitations. Then, all mice were stochastically divided into 5 groups using random number tables available online (https://www.random-online.com/, accessed on 26 December 2021), including: (1) C group, a control group treated with normal saline for 7 consecutive days (n = 10); (2) M group, a model group with intraperitoneal injection of 20 mg/kg/day MPTP (Sigma-Aldrich, Taufkirchen, Germany, M0896) for 7 consecutive days (n = 10); (3) L group, treated with MPTP and 0.4 mg/kg/day liraglutide for 7 consecutive days (n = 10); (4) R group, treated with MPTP and 109 colony-forming unit (CFU) L. lactis MG1363 for 7 consecutive days via gavage (n = 10); (5) RG group, treated with MPTP and 109 CFUL. lactis MG1363-pMG36e-GLP-1 for 7 consecutive days via gavage (n = 10). All animals survived treatment and all animal experiments were administered from 9:00 to 12:00 in the morning to reduce systematic errors. REF000897 ICD-11: 8A00 Parkinson disease CELL10116; CELL10005 Colon tissues; brain tissues Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique00353 Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence. Inducer . Up regulation . . Driver Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments. REF000481 ICD-11: 8A00 Parkinson disease CELL00042 SH-SY5Y Apoptosis (hsa04210); Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique01568 Dysregulated ferroptosis is closely associated with Parkinson's disease (PD) progression. NEAT1 functioned as a sponge to suppress miR-150-5p expression. Moreover, miR-150-5p overexpression suppressed ferroptosis in PD cell model. And miR-150-5p regulated SLC7A11 expression by directly binding to BAP1. . . . Up regulation Driver Driver . REF000777 ICD-11: 8A00.0 Parkinson's Disease CELL00127 SKNSH Ferroptosis (hsa04216) Cell ferroptosis
unique01569 Dysregulated ferroptosis is closely associated with Parkinson's disease (PD) progression. NEAT1 functioned as a sponge to suppress miR-150-5p expression. Moreover, miR-150-5p overexpression suppressed ferroptosis in PD cell model. And miR-150-5p regulated SLC7A11 expression by directly binding to BAP1. . . . Down regulation Suppressor Driver . REF000777 ICD-11: 8A00.0 Parkinson's Disease CELL00127 SKNSH Ferroptosis (hsa04216) Cell ferroptosis
unique01101 MiR335 promotes ferroptosis by targeting FTH1 inin vitroandin vivomodels of Parkinson's disease, providing a potential therapeutic target for the treatment of PD. Mechanistically, miR335 enhanced ferroptosis through the degradation of FTH1 to increase iron release, lipid peroxidation and reactive oxygen species (ROS) accumulation, and to decrease mitochondrial membrane potential (MMP). . . . Down regulation Driver Marker/Suppressor A total of 48 male Sprague-Dawley rats (weighing, 180-220 g; 6-8 weeks of age) were purchased from the Animal Center of Guangzhou University of Chinese Medicine (Guangzhou, China). The rats were anesthetized (100 mg/kg ketamine and 10 mg/kg xylazine, intraperitoneal injection) and placed in a stereotaxic apparatus with the skull flat. An intracerebral injection of 6-OHDA was performed at 2 sites in the right SN pars compacta (SNpc) and ventral tegmental area (VTA): Anteroposterior (A/P)=-4.9 mm; mediolateral (M/L)=-1.9 mm; dorsoventral (D/V)=-7.5 mm; and anteroposterior (A/P)=-4.9 mm; mediolateral (M/L)=-1.1 mm; dorsoventral (D/V)=8.0 mm. During the surgery, body temperature was maintained at ~36.5 using a heating pad. All rats received meticulous post-operative care. REF000341 ICD-11: 8A00 Parkinson disease CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00151 6-hydroxydopamine (6-OHDA) treatment-induced ferroptosis in SH-SY5Y cells mainly by disturbing the protein expression of GPX4 and ACSL4. Collectively, the activation of the p62-Keap1-Nrf2 pathway prevents 6-OHDA-induced ferroptosis in SH-SY5Y cells, targeting this pathway in combination with a pharmacological inhibitor of ferroptosis can be a potential approach for parkinson's disease therapy. Inducer . Down regulation . . Suppressor The AB strain of wild-type zebrafish (Danio rerio) was applied in this study. Zebrafish larvae at 4 dpf (days post-fertilization) were co-incubated with 250 uM 6-OHDA or 1.5 ug/mL nomifensine (Nomi, a dopamine transporter inhibitor) in 6-well plates at a density of 30 zebrafish embryos per group for 2 days and the medium was refreshed every day. The swimming total distance of each fish was recorded for 10 min and was analyzed by an automated video tracking system. REF000206 ICD-11: 8A00 Parkinson disease CELL00042 SH-SY5Y Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01190 This study investigated the mechanism by which PD-specific SE driven SNX5 promoted the ferroptosis level in Parkinson's disease models. The results showed that the GPX4 expression level significantly reduced. . . . Down regulation Driver Suppressor All animal maintenance and experiments were approved by The Ethical Committee of Guangzhou University of Chinese Medicine. A total of 36 SD rats (Sprague-Dawley; male; 230-260 g; 8-9-weeks old) were divided randomly into two study groups (n = 18 rats/group), i.e., the sham group (unilateral injection of the equal volume of saline) and model group (unilateral injection of 20 g of 6-OHDA). All surgical procedures were performed under (10 mg/kgxylazine, and 100 mg/kg ketamine, intraperitoneal administration) anesthesia using stereotactic apparatus (RWD, Shenzhen, China). The rats received either unilateral injections of 5 ul of 6-OHDA (Sigma-Aldrich, Germany; 4 ug/ul, dissolved in PBS) or 5 ul of saline into MFB (left medial forebrain bundle) at the rate of 1 ul/min. Injection coordinates were as follows (with reference to bregma): anteroposterior (A/P) = - 2.2 mm, lateral (LAT) = 1.5 mm, and dorsoventral (D/V) = 8.0 mm. The rats were placed in animal holding room (humidity: 50 ± 5%; temperature: 21 ± 1 ; 12-h dark/light cycle). REF000433 ICD-11: 8A00.0 Parkinson's Disease CELL00597 PC12 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00088 Gastrodin induced GPX4, Nrf2 and HO-1 expression to protect C6 cells from H2O2-induced ferroptosis. Gastrodin pretreatment effectively reduced H2O2-induced oxidative damage, indicating gastrodin is a potential antioxidant that reduced cytotoxic ROS. The role of gastrodin in ferroptosis presents a new perspective for understanding parkinson's disease. Suppressor . Up regulation . . Driver/Suppressor . REF000141 ICD-11: 8A00 Parkinson disease CELL00593 C6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00352 Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence. Inducer . Up regulation . . Driver Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments. REF000481 ICD-11: 8A00 Parkinson disease CELL00042 SH-SY5Y Apoptosis (hsa04210); Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00087 Gastrodin induced GPX4, Nrf2 and HO-1 expression to protect C6 cells from H2O2-induced ferroptosis. Gastrodin pretreatment effectively reduced H2O2-induced oxidative damage, indicating gastrodin is a potential antioxidant that reduced cytotoxic ROS. The role of gastrodin in ferroptosis presents a new perspective for understanding parkinson's disease. Suppressor . Up regulation . . Marker/Suppressor . REF000141 ICD-11: 8A00 Parkinson disease CELL00593 C6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00351 Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence. Inducer . Up regulation . . Marker Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments. REF000481 ICD-11: 8A00 Parkinson disease CELL00042 SH-SY5Y Apoptosis (hsa04210); Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00964 KD of DJ-1 (PARK7) increases ferroptosis as PTGS2 levels increased. DJ-1 mutant neuronal cells experience high levels of ferroptosis, which might establish a potential mechanism via which DJ-1 could regulate early-onset recessive Parkinsons disease. . . . Up regulation Suppressor Marker Tumors were established by a subcutaneous injection of shRNA (control or DJ-1 KD) transfected H1299 cells (1,000,000/200 uL) into BALB/c female athymic nude mice (5 weeks, National Rodent Laboratory Animal Resource, Shanghai, China). Twelve days after injection, mice were randomly allocated into different groups and treated with vehicle (0.625% DMSO/99.375% HBSS (pH = 2)) or 30 mg/kg PE (tail intravenous injection, once every other day) for 16 days before the final tumor size was measured in all groups. REF000144 ICD-11: 8A00 Parkinson disease CELL00056; CELL00045; CELL00120; CELL00117; CELL00384; CELL00021; CELL00412; CELL00070; CELL00057 H1299; A549; PANC1; H292; H838; 786-O; KHOS; A2780; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00622 Epigallocatechin-3-Gallate (EGCG) pretreatment counteracted 6-OHDA-induced increased expression of divalent metal transporter-1 (DMT1) and hepcidin and decreased expression of the iron-export protein ferroportin 1 (Fpn1), leading to a 28% reduction in Fe2+ uptake. EGCG inhibits iron overload, decreased LPO, and increased GSH levels in Parkinson disease models, which are the three major hallmarks of ferroptosis. Suppressor . Up regulation . . Driver . REF000846 ICD-11: 8A00 Parkinson disease . . Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00623 Epigallocatechin-3-Gallate (EGCG) pretreatment counteracted 6-OHDA-induced increased expression of divalent metal transporter-1 (DMT1) and hepcidin and decreased expression of the iron-export protein ferroportin 1 (Fpn1), leading to a 28% reduction in Fe2+ uptake. EGCG inhibits iron overload, decreased LPO, and increased GSH levels in Parkinson disease models, which are the three major hallmarks of ferroptosis. Suppressor . Down regulation . . Marker/Suppressor . REF000846 ICD-11: 8A00 Parkinson disease . . Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique00354 Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence. Inducer . Down regulation . . Suppressor Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments. REF000481 ICD-11: 8A00 Parkinson disease CELL00042 SH-SY5Y Apoptosis (hsa04210); Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00672 L. lactis MG1363-pMG36e-GLP-1 exerts neurotrophic effects via activating the Keap1/Nrf2/GPX4 signalling pathway to down-regulate ACSL4 and up-regulate FSP1 to suppress ferroptosis. These results indicated that the neurotrophic effects of the next-generation probiotics L. lactis MG1363-pMG36e-GLP-1 against MPTP-induced Parkinsonism are mediated by modulating oxidative stress, inhibiting ferroptosis, and redressing dysbiosis. Suppressor . Up regulation . . Suppressor Fifty male C57BL/6 mice provided by Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China) resided in an animal house (temperature 26 ± 1 , humidity 50 ± 10%), in which the light was on for 12 h and off for 12 h. Mice were acclimatised for 1 week and allowed water and animal food with no limitations. Then, all mice were stochastically divided into 5 groups using random number tables available online (https://www.random-online.com/, accessed on 26 December 2021), including: (1) C group, a control group treated with normal saline for 7 consecutive days (n = 10); (2) M group, a model group with intraperitoneal injection of 20 mg/kg/day MPTP (Sigma-Aldrich, Taufkirchen, Germany, M0896) for 7 consecutive days (n = 10); (3) L group, treated with MPTP and 0.4 mg/kg/day liraglutide for 7 consecutive days (n = 10); (4) R group, treated with MPTP and 109 colony-forming unit (CFU) L. lactis MG1363 for 7 consecutive days via gavage (n = 10); (5) RG group, treated with MPTP and 109 CFUL. lactis MG1363-pMG36e-GLP-1 for 7 consecutive days via gavage (n = 10). All animals survived treatment and all animal experiments were administered from 9:00 to 12:00 in the morning to reduce systematic errors. REF000897 ICD-11: 8A00 Parkinson disease CELL10116; CELL10005 Colon tissues; brain tissues Pathways in cancer (hsa05200); Ferroptosis (hsa04216) Cell ferroptosis
unique00124 Ferroptosis was probably involved in the pathogenesis of parkinson's disease (PD). Clioquinol (CQ) can decrease the excessive iron in the SN to normal level and directly protect DA neurons against oxidative stress probably by activating the AKT/mTOR survival pathway and blocking p53-medicated cell death. Suppressor Up regulation . . Suppressor . In total, twelve healthy adult rhesus monkeys (Macaca mulatta lasiotis, aged 4-5 years, and weighed 3.5-5 kg at the start of the study) were obtained from Sichuan Primed Biological Technology Co., Ltd. Monkeys were randomly divided into two groups: normal (control) group (n = 3) and MPTP group (n = 9). Monkeys from MPTP group were administered with MPTP by intramuscular injection daily at the beginning of the study, and then the MPTP dose was gradually added to 0.5 mg/kg at the end of the experiment. Monkeys from control group were injected with saline instead, and the other conditions were the same with MPTP group. REF000176 ICD-11: 8A00 Parkinson disease CELL00127 SK-N-SH Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
dupunique00124 Ferroptosis was probably involved in the pathogenesis of parkinson's disease (PD). Clioquinol (CQ) can decrease the excessive iron in the SN to normal level and directly protect DA neurons against oxidative stress probably by activating the AKT/mTOR survival pathway and blocking p53-medicated cell death. Suppressor Down regulation . . Driver . In total, twelve healthy adult rhesus monkeys (Macaca mulatta lasiotis, aged 4-5 years, and weighed 3.5-5 kg at the start of the study) were obtained from Sichuan Primed Biological Technology Co., Ltd. Monkeys were randomly divided into two groups: normal (control) group (n = 3) and MPTP group (n = 9). Monkeys from MPTP group were administered with MPTP by intramuscular injection daily at the beginning of the study, and then the MPTP dose was gradually added to 0.5 mg/kg at the end of the experiment. Monkeys from control group were injected with saline instead, and the other conditions were the same with MPTP group. REF000176 ICD-11: 8A00 Parkinson disease CELL00127 SK-N-SH Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00103 Ferroptosis firstly occurred in a relatively low concentration of ferric ammonium citrate (FAC)-treated group, and then apoptosis appeared in response to the increased iron doses. This was also confirmed in vivo in parkinson's disease transgenic mice and the underlying mechanism might be associated with the p53 signaling pathway, but not MAPK signaling pathway. Inducer Up regulation . . Driver . Human a-synuclein (a-Syn) A53T overexpressiontransgenic mice(B6; C3-Tg (Prnp-SNCA*A53T) 83Vle/J) were originally obtained in breeding pairs from the Jackson Laboratory (004479) to generate a stable breeding colony. Animals were raised according to SPF level, kept at constant temperature (20 ± 2) , constant humidity (50 ± 10%), day and night cycle light (12-12 h), with free access to food and water. REF000156 ICD-11: 8A00 Parkinson disease CELL00585 MES23.5 Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00512 Forsythoside A treatment exerted anti-ferroptosis and anti-neuroinflammatory effects in erastin-stimulated HT22 cells, and the Nrf2/GPX4 axis played a key role in these effects. Collectively, these results demonstrate the protective effects of FA and highlight its therapeutic potential as a drug component for AD ( Alzheimer's disease) treatment. Suppressor . Up regulation . . Suppressor All animal experiments were approved by the Animal Ethics Committee of Jilin University (permit No. SY201905013) and were conducted in compliance with the ARRIVE guidelines. Eight-month-old B6C3-Tg (APPswePSEN1dE9)/Nju double transgenic male mice (APP/PS1) (genotype: (Appswe) T, (Psen1) T) and age-matched wild-type (WT) (genotype: (Appswe) W, (Psen1) W) male mice were purchased from Nanjing Biomedical Research Institute of Nanjing University. All mice were individually housed at 24 with food and drinking water availablead libitum. After 1 week of adaption in the new environment, WT mice received oral administration of normal saline (10 mL/kg) and were designated as the control group (n = 12). APP/PS1 mice were randomly divided into two groups: the model group (n = 12) received oral administration of normal saline (10 mL/kg) and the agent-treated group (n = 12) received oral treatment with 30 mg/kg FA (L-012-171216, 98.83% purity, Chengdu Herbpurify Co., Ltd., Chengdu, China) beginning on day 8. After 30-day treatment, behavioral experiments were serially performed. The entire treatment protocol lasted for 42 days. Blood samples were collected from the caudal vein. After euthanasia via CO2 inhalation, organs including the brain, liver, spleen, and kidney were collected for further analysis. REF000699 ICD-11: 8A20 Alzheimer's disease CELL00549; CELL00552; CELL00544 HT22; N2a; BV2 NF-kappa B signaling pathway (hsa04064); Ferroptosis (hsa04216) Cell ferroptosis
unique00343 Ginkgolide B attenuated Alzheimer's disease (AD)-related cognitive impairment through the regulation of oxidative stress, neuroinflammation and ferroptosis, and that GB-induced protection in AD is dependent on the inhibition of ferroptosis. Furthermore, the involvement of Nrf2/GPX4 pathway-regulated ferroptosis in the GB-related protective effects on the AD mouse model. Suppressor . Up regulation . . Suppressor Male 6-month-old senescence-resistant R1 (SAMR1) and SAMP8 mice (weight, 28-35 g) were purchased from Beijing SPF Biotechnology. First, mice were placed in the center of an empty testing arena (40 x 40 x 40 cm) and allowed to move freely for adaptation. Next, in the training stage, two similar objects were presented in the testing arena and mice were allowed to explore for 10 min, for 3 consecutive days. On day 4, one of the two familiar objects was replaced by a new object. The time of exploring a novel object or familiar object in 10 min was recorded. REF000468 ICD-11: 8A20 Alzheimer's disease CELL10127 hippocampus tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00771 Salidroside alleviates cognitive impairment and inhibits neuronal ferroptosis in Alzheimer's disease. The underlying mechanisms may involve the Nrf2/GPX4 axis activation and reduction in CD8T cells infiltration. Suppressor . Up regulation . . Suppressor SAMP8 mice were employed as an AD model and were treated with salidroside for 12 weeks. Behavioral tests, immunohistochemistry, HE and Nissl staining, immunofluorescence, transmission electron microscopy, quantitative proteomics, bioinformatic analysis, flow cytometry, iron staining,western blotting, andmolecular dockingwere performed. REF000992 ICD-11: 8A20 Alzheimer's disease CELL10115 CD8T cell Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00345 Tetrahydroxy stilbene glycoside (TSG) promoted the activation of GSH/GPX4/ROS and Keap1/Nrf2/ARE signaling pathways. Notably, markers related to ferroptosis including increased lipid peroxidation, enhanced neuroinflammation such as NLRP3, and also the expression of DMT1, ACSL4 and NCOA4, were reduced by TSG administration. In addition, TSG enhanced antioxidative stress via the upregulation of SOD, and the expression of FTH1, CD98 and xCT. Hence, TSG should be taken into consideration during treatment of Alzheimer's disease in the future. Suppressor . Up regulation . . Suppressor APPswe/PSEN1dE9 (APP/PS1) double transgene mice, which were generated by the introduction of human APPswe and PS1-dE9 mutations onto the C57BL/6 background and also wild type (WT) littermates, aged 5 months, were purchased from Beijing HFK Bioscience Co., Ltd. (Beijing, China). The mice received food and water ad libitum under standard husbandry conditions (22-25, 55-65% relative humidity, and 12h/12h lightdark cycle) and acclimated 1 week for the experiments. Mice were randomly divided into 5 groups, including WT control group, APP/PS1 model group, and APP/PS1 + TSG (60, 120 and 180 mg/kg) different dosage groups. Mice were orally treated with TSG every other day for 2 months. WT and model groups were treated with equivalent vehicle. REF000469 ICD-11: 8A20 Alzheimer's disease CELL10127 hippocampus tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Pathways in cancer (hsa05200) Cell ferroptosis
unique00551 Salidroside plays a neuroprotective role by inhibiting neuronal ferroptosis in A1-42-induced Alzheimer's disease mice and Glu-injured HT22 cells, and its mechanism is related to activation of the Nrf2/HO1 signaling pathway. Suppressor . Up regulation . . Suppressor B6.1291-Nfe2l2tm1Ywk/J (Nrf2-/-mice, 017009)and wild-type C57BL/6 were originally from the Jackson Laboratory. Grouping and administration were started when weighing approximately 28-33 g. All mice were housed in a laboratory environment with free access to adequate food and water under a 12 h/12 h light/dark cycle at 22 ± 1 and 55 ± 5% humidity. All procedures conformed to the protocols of the Animal Welfare Commission and Ethical Committee of Southern Medical University. The Nrf2-/- mice were identified by genotyping as shown in Fig.1B. WT and Nrf2-/- mice were randomly assigned to 32 groups (3 groups for WT mice and 3 groups for Nrf2-/- mice) as follows: a sham group, sham + Ab1-42 group, and Salidroside + Ab1-42 group. REF000771 ICD-11: 8A20 Alzheimer's disease CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00511 Forsythoside A treatment exerted anti-ferroptosis and anti-neuroinflammatory effects in erastin-stimulated HT22 cells, and the Nrf2/GPX4 axis played a key role in these effects. Collectively, these results demonstrate the protective effects of FA and highlight its therapeutic potential as a drug component for AD ( Alzheimer's disease) treatment. Suppressor . Up regulation . . Marker/Suppressor All animal experiments were approved by the Animal Ethics Committee of Jilin University (permit No. SY201905013) and were conducted in compliance with the ARRIVE guidelines. Eight-month-old B6C3-Tg (APPswePSEN1dE9)/Nju double transgenic male mice (APP/PS1) (genotype: (Appswe) T, (Psen1) T) and age-matched wild-type (WT) (genotype: (Appswe) W, (Psen1) W) male mice were purchased from Nanjing Biomedical Research Institute of Nanjing University. All mice were individually housed at 24 with food and drinking water availablead libitum. After 1 week of adaption in the new environment, WT mice received oral administration of normal saline (10 mL/kg) and were designated as the control group (n = 12). APP/PS1 mice were randomly divided into two groups: the model group (n = 12) received oral administration of normal saline (10 mL/kg) and the agent-treated group (n = 12) received oral treatment with 30 mg/kg FA (L-012-171216, 98.83% purity, Chengdu Herbpurify Co., Ltd., Chengdu, China) beginning on day 8. After 30-day treatment, behavioral experiments were serially performed. The entire treatment protocol lasted for 42 days. Blood samples were collected from the caudal vein. After euthanasia via CO2 inhalation, organs including the brain, liver, spleen, and kidney were collected for further analysis. REF000699 ICD-11: 8A20 Alzheimer's disease CELL00549; CELL00552; CELL00544 HT22; N2a; BV2 NF-kappa B signaling pathway (hsa04064); Ferroptosis (hsa04216) Cell ferroptosis
unique00344 Ginkgolide B attenuated Alzheimer's disease (AD)-related cognitive impairment through the regulation of oxidative stress, neuroinflammation and ferroptosis, and that GB-induced protection in AD is dependent on the inhibition of ferroptosis. Furthermore, the involvement of Nrf2/GPX4 pathway-regulated ferroptosis in the GB-related protective effects on the AD mouse model. Suppressor . Up regulation . . Marker/Suppressor Male 6-month-old senescence-resistant R1 (SAMR1) and SAMP8 mice (weight, 28-35 g) were purchased from Beijing SPF Biotechnology. First, mice were placed in the center of an empty testing arena (40 x 40 x 40 cm) and allowed to move freely for adaptation. Next, in the training stage, two similar objects were presented in the testing arena and mice were allowed to explore for 10 min, for 3 consecutive days. On day 4, one of the two familiar objects was replaced by a new object. The time of exploring a novel object or familiar object in 10 min was recorded. REF000468 ICD-11: 8A20 Alzheimer's disease CELL10127 hippocampus tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00770 Salidroside alleviates cognitive impairment and inhibits neuronal ferroptosis in Alzheimer's disease. The underlying mechanisms may involve the Nrf2/GPX4 axis activation and reduction in CD8T cells infiltration. Suppressor . Up regulation . . Marker/Suppressor SAMP8 mice were employed as an AD model and were treated with salidroside for 12 weeks. Behavioral tests, immunohistochemistry, HE and Nissl staining, immunofluorescence, transmission electron microscopy, quantitative proteomics, bioinformatic analysis, flow cytometry, iron staining,western blotting, andmolecular dockingwere performed. REF000992 ICD-11: 8A20 Alzheimer's disease CELL10115 CD8T cell Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00550 Salidroside plays a neuroprotective role by inhibiting neuronal ferroptosis in A1-42-induced Alzheimer's disease mice and Glu-injured HT22 cells, and its mechanism is related to activation of the Nrf2/HO1 signaling pathway. Suppressor . Up regulation . . Marker/Suppressor B6.1291-Nfe2l2tm1Ywk/J (Nrf2-/-mice, 017009)and wild-type C57BL/6 were originally from the Jackson Laboratory. Grouping and administration were started when weighing approximately 28-33 g. All mice were housed in a laboratory environment with free access to adequate food and water under a 12 h/12 h light/dark cycle at 22 ± 1 and 55 ± 5% humidity. All procedures conformed to the protocols of the Animal Welfare Commission and Ethical Committee of Southern Medical University. The Nrf2-/- mice were identified by genotyping as shown in Fig.1B. WT and Nrf2-/- mice were randomly assigned to 32 groups (3 groups for WT mice and 3 groups for Nrf2-/- mice) as follows: a sham group, sham + Ab1-42 group, and Salidroside + Ab1-42 group. REF000771 ICD-11: 8A20 Alzheimer's disease CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00011 Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by neurofibrillary tangles (NFTs) composed of Tau protein. a-Lipoic acid (LA) plays a role in inhibiting Tau hyperphosphorylation and neuronal loss, including ferroptosis. After LA administration, TFR expression level was downregulated while Fpn1 level was upregulated, thereby reducing the iron overload. Suppressor . Up regulation . . Marker/Suppressor The P301S transgenic mice [B6C3-Tg (Prnp-MAPT*P301S) PS19 Vle/J], originally obtained from the Jackson laboratory (Bar Harbor, ME, USA), were used as a model of tauopathy. The female mice at the age of 5 months were randomly allocated to three treatment groups (7 mice/group) corresponding to vehicle control, 3 mg/kg LA (T5625, Sigma, St. Louis, MO; the dosage was calculated everyday based on weight), and 10 mg/kg LA. LA was administered by intraperitoneal injection once per day (no injection was administered one day every three days), and vehicle control mice received physiological saline. REF000030 ICD-11: 8A20 Alzheimer's disease CELL10005 Brain tissues Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00010 Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by neurofibrillary tangles (NFTs) composed of Tau protein. a-Lipoic acid (LA) plays a role in inhibiting Tau hyperphosphorylation and neuronal loss, including ferroptosis. After LA administration, TFR expression level was downregulated while Fpn1 level was upregulated, thereby reducing the iron overload. Suppressor . Down regulation . . Marker/Suppressor/Driver The P301S transgenic mice [B6C3-Tg (Prnp-MAPT*P301S) PS19 Vle/J], originally obtained from the Jackson laboratory (Bar Harbor, ME, USA), were used as a model of tauopathy. The female mice at the age of 5 months were randomly allocated to three treatment groups (7 mice/group) corresponding to vehicle control, 3 mg/kg LA (T5625, Sigma, St. Louis, MO; the dosage was calculated everyday based on weight), and 10 mg/kg LA. LA was administered by intraperitoneal injection once per day (no injection was administered one day every three days), and vehicle control mice received physiological saline. REF000030 ICD-11: 8A20 Alzheimer's disease CELL10005 Brain tissues Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01769 MiR-367-3p can be delivered by BMSC-Exos into microglia, where miR-367-3p inhibits EZH2 expression and activates the expression of SLC7A11, suppressing microglial ferroptosis and relieving the symptoms of EAE. Experimental autoimmune encephalomyelitis (EAE) is a typical animal model of multiple sclerosis. . . . Up regulation Suppressor Suppressor Female C57BL6 mice were randomized into four groups (n = 8/group): the control group (non-EAE mice), the EAE group (EAE mice injected intrathecally with 5 uL PBS when symptoms appeared), the EAE + BMSCs-Exo + mimic negative control (NC) group (EAE mice injected intrathecally with Exos from bone MSCs (BMSCs) transfected with mimic NC [5 uL, 2 ug/L in PBS] when symptoms appeared), and the EAE + BMSCs-Exo + miR-367-3p mimic group (EAE mice injected intrathecally with Exos from BMSCs transfected with miR-367-3p mimic [5 uL, 2 ug/L in PBS] when symptoms appeared). REF000998 ICD-11: 8A40 Multiple sclerosis CELL10003; CELL00544 BMSCs; BV2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01768 MiR-367-3p can be delivered by BMSC-Exos into microglia, where miR-367-3p inhibits EZH2 expression and activates the expression of SLC7A11, suppressing microglial ferroptosis and relieving the symptoms of EAE. Experimental autoimmune encephalomyelitis (EAE) is a typical animal model of multiple sclerosis. . . . Down regulation Driver Suppressor Female C57BL6 mice were randomized into four groups (n = 8/group): the control group (non-EAE mice), the EAE group (EAE mice injected intrathecally with 5 uL PBS when symptoms appeared), the EAE + BMSCs-Exo + mimic negative control (NC) group (EAE mice injected intrathecally with Exos from bone MSCs (BMSCs) transfected with mimic NC [5 uL, 2 ug/L in PBS] when symptoms appeared), and the EAE + BMSCs-Exo + miR-367-3p mimic group (EAE mice injected intrathecally with Exos from BMSCs transfected with miR-367-3p mimic [5 uL, 2 ug/L in PBS] when symptoms appeared). REF000998 ICD-11: 8A40 Multiple sclerosis CELL10003; CELL00544 BMSCs; BV2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00382 Klotho overexpression inhibits ferroptosis in temporal lobe epilepsy (TLE) with cognitive deficits and has a neuroprotective effect. Moreover, for the first time, we found that klotho overexpression inhibits ferroptosis and iron overload in TLE with cognitive deficits. In addition, klotho overexpression down-regulated the expression of DMT1 and up-regulated FPN expression which regulated iron metabolism balance. Suppressor . Down regulation . . Driver Adult male Sprague-Dawley (SD) rats aged between 6 and 8 weeks old and weighing between 280 and 320 g were purchased from Hunan slake jingda laboratory animal company (Changsha, China) and used in this study. Under a 12 h light/dark cycle, rats had free access to water and food and were maintained in a room with controlled temperature, humidity. These rats were adapted to the environment for at least 2 week before we began to enter the experimental procedure. REF000519 ICD-11: 8A61 Temporal lobe epilepsy CELL10171 Hippocampus tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00381 Klotho overexpression inhibits ferroptosis in temporal lobe epilepsy (TLE) with cognitive deficits and has a neuroprotective effect. Moreover, for the first time, we found that klotho overexpression inhibits ferroptosis and iron overload in TLE with cognitive deficits. In addition, klotho overexpression down-regulated the expression of DMT1 and up-regulated FPN expression which regulated iron metabolism balance. Suppressor . Up regulation . . Marker/Suppressor Adult male Sprague-Dawley (SD) rats aged between 6 and 8 weeks old and weighing between 280 and 320 g were purchased from Hunan slake jingda laboratory animal company (Changsha, China) and used in this study. Under a 12 h light/dark cycle, rats had free access to water and food and were maintained in a room with controlled temperature, humidity. These rats were adapted to the environment for at least 2 week before we began to enter the experimental procedure. REF000519 ICD-11: 8A61 Temporal lobe epilepsy CELL10171 Hippocampus tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00038 Baicalein, as a naturel bioactive compound, could ameliorate behavioral seizures and play a key neuroprotective role in FeCl3-induced posttraumatic epileptic seizures through inhibiting ferroptosis and its neuroprotection might be related to suppression of 12-LOX/15-LOX. Suppressor . Down regulation . . Driver All adult male C57/BL6 mice weighing 18-22g were obtained from the Experimental Animal Center of Central South University, China. Animals were randomly divided into six groups as follows: 1) control group (n = 6) was given vehicle intracranial injection (PBS 5 ul); 2) FeCl3 group (n = 6) was given 5 ul 50 mM FeCl3; 3) and 4) baicalein groups were pretreated with baicalein 50 mg/kg (n = 6) and 100 mg/kg (n = 6) 30 min prior to FeCl3 administration, respectively; 5) ferroptosis inhibitor group (n = 6) was administered continuously with 10 mg/kg Lipo-1 3 d prior to FeCl3 administration; and 6) baicalein administration group (n = 6) was given 100 mg/kg baicalein once by intraperitoneal injection 30 min prior to 5 ul PBS administration. REF000074 ICD-11: 8A66 Posttraumatic epileptic seizures CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00037 Baicalein, as a naturel bioactive compound, could ameliorate behavioral seizures and play a key neuroprotective role in FeCl3-induced posttraumatic epileptic seizures through inhibiting ferroptosis and its neuroprotection might be related to suppression of 12-LOX/15-LOX. Suppressor . Down regulation . . Driver All adult male C57/BL6 mice weighing 18-22g were obtained from the Experimental Animal Center of Central South University, China. Animals were randomly divided into six groups as follows: 1) control group (n = 6) was given vehicle intracranial injection (PBS 5 ul); 2) FeCl3 group (n = 6) was given 5 ul 50 mM FeCl3; 3) and 4) baicalein groups were pretreated with baicalein 50 mg/kg (n = 6) and 100 mg/kg (n = 6) 30 min prior to FeCl3 administration, respectively; 5) ferroptosis inhibitor group (n = 6) was administered continuously with 10 mg/kg Lipo-1 3 d prior to FeCl3 administration; and 6) baicalein administration group (n = 6) was given 100 mg/kg baicalein once by intraperitoneal injection 30 min prior to 5 ul PBS administration. REF000074 ICD-11: 8A66 Posttraumatic epileptic seizures CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00432 Vitamin E treatment was associated with decreased epileptic grade, seizure latency, and number of seizures in the PTZ-kindled epileptic model. Vitamin E treatment also decreased 15-LOX expression, inhibited MDA and iron accumulation, and increased GPX4 and GSH expression. In conclusion, vitamin E can reduce neuronal ferroptosis and seizures by inhibiting 15-LOX expression. Suppressor . Down regulation . . Driver Sixty-four male Sprague-Dawley (SD) rats (5-6 weeks old) were provided by Shandong Jinan Pengyue Experimental Animal Breeding Co. Ltd. Rats were randomly divided into four groups (n = 16/group): (i) Control group rats received normal saline (NS) administered intraperitoneally (i.p.); (ii) PTZ group rats received PTZ (35 mg/kg, i.p.; Sigma-Aldrich, USA) [7]; (iii) Vitamin E+PTZ group rats received vitamin E (200 mg/kg, i.p.; Sigma-Aldrich, St. Louis, MO, USA) 30 min before PTZ injection; (iv) Fer-1+PTZ group rats received Fer-1 (2.5 umol/g, i.p.; Selleck, Houston, TX, USA) 30 min before PTZ injection. All drugs were administered every other day for a total of 15 injections. REF000582 ICD-11: 8A66 Epilepsy CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01068 Lapatinib exerted neuroprotection via restoring glutathione peroxidase 4 (GPX4). Treatment with GPX4 inhibitor ras-selective lethal small molecule 3 (RSL3) abrogated its anti-ferroptotic potential. It is concluded that lapatinib has neuroprotective potential against epileptic seizures via suppressing GPX4-mediated ferroptosis. Suppressor . Up regulation . . Suppressor Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were obtained from the Animal Unit of Central South University. After anesthetization by intraperitoneal injection of 10% chloral hydrate (v/w), the mice were fixed on a stereotactic instrument and stereotactically injected with KA (250 ng/ul) into the hippocampus. KA (1 ul) was injected slowly for 5 min and positioned in the hippocampus (AP-2.0 mm, ML-1.3 mm, V-1.2 mm). After injection, the needle was left in place for additional 10 min to avoid drug reflux. The mice were randomly divided into six experimental groups: 1) sham operation group that received 1 ul PBS injection (5 animals); 2) mice were pretreated p. o. for 21 days on a twice-daily schedule with 100 mg/kg lapatinib alone before PBS administration (5 animals); 3) KA-treated group was injected KA (5 animals); 4) and 5) lapatinib groups were received with 50 mg/kg (5 animals) and 100 mg/kg (5 animals) lapatinib for 21 days before KA treatment, respectively; 6) this group was given i. p. for 14 days with ferroptosis inhibitor (3 mg/kg Fer-1) before KA administration. REF000290 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00594 Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures in Epilepsy. Suppressor Down regulation . . Driver . Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. REF000825 ICD-11: 8A66 Epilepsy CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00112 Apigenin can efficiently reduce the expression of intracellular MPO and increase the levels of GPX4 and SIRT1, thereby conferring neuroprotection through regulation of kainic acid (KA)-induced ferroptosis. And the level of Ac-p53 inside the brains treated with apigenin was down-regulated, suggesting that the p53-mediated ferroptosis pathway might be blocked. Overall, apigenin was screened and confirmed as an efficient lead compound for epilepsy prevention and treatment. Suppressor Up regulation . . Suppressor . 5-weeks-old kainate (KA)-induced BALB/c nude mice, a widely used epilepsy mouse model, were performed with intraperitoneal (i.p.) injection of KA (6 mg/kg). Pre-treatment 21 with antioxidant apigenin (60 mg/Kg, 2 days) or post-treatment with apigenin (60 mg/Kg, 1 day), mice were injected with KA (6 mg/kg) via intraperitoneal (i.p.) injection, and then HCP (0.5 mg/Kg) were injected by intravenous (i.v.) injection. In vivo and Ex vivo fluorescence images of relative ClO levels in mice brains 5, 15, 30, 45, and 60 min post injection of HCP were further performed by using the IVIS Spectrum imaging system (Nanjing University) with an excitation filter of 430 nm and the collection wavelength range is from 500-600 nm. REF000165 ICD-11: 8A66 Epilepsy CELL00042 SH-SY5Y Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01202 LncRNA H19 was overexpressed in Intracerebral hemorrhage (ICH). Knockdown of H19 promoted cell proliferation and suppressed BMVECs ferroptosis by regulating the miR-106b-5p/ACSL4 axis. Therefore, H19 knockdown may be a promising therapeutic strategy for ICH. . . . Up regulation Driver Driver . REF000458 ICD-11: 8B00 Intracerebral haemorrhage CELL10112 Brain microvascular endothelial cells (BMVECs) Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01203 LncRNA H19 was overexpressed in Intracerebral hemorrhage (ICH). Knockdown of H19 promoted cell proliferation and suppressed BMVECs ferroptosis by regulating the miR-106b-5p/ACSL4 axis. Therefore, H19 knockdown may be a promising therapeutic strategy for ICH. . . . Down regulation Suppressor Driver . REF000458 ICD-11: 8B00 Intracerebral haemorrhage CELL10112 Brain microvascular endothelial cells (BMVECs) Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00456 20-hydroxyeicosatetraenoic acid induces ferroptosis in OHSCs, and inhibition of 20-HETE synthesis improves Intracerebral hemorrhage (ICH) outcome and attenuates markers of ferroptosis, such as mobile iron, lipid peroxidation, and decreased GPX4. Inducer . Down regulation . . Suppressor Adult male C57BL/6J mice were obtained from the Jackson Laboratory (Bar Harbor, ME USA). Mice at 10-12 weeks of age were anesthetized by 1-3% isoflurane inhalation and ventilated with oxygen-enriched air (20% O2:80% air). The right striatum of mice was injected with 0.5 ul of 0.075 U collagenase VII-S (MilliporeSigma, St. Louis, MO, USA) at 0.1 ul per minute. Injections were administered at 0.5 mm anterior and 2.2 mm lateral of the bregma, and 3.0 mm in depth, as previously described. Sham-operated mice received the same treatment, including needle insertion, but were not injected with collagenase. Mice that died before the end of the surgery or shortly thereafter were excluded. REF000600 ICD-11: 8B00 Intracerebral haemorrhage CELL10137 OHSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00271 Baicalin significantly increased the mRNA expression of GPX4 and SLC7A11 in the perihematoma brain tissues of intracerebral hemorrhage (ICH) model mice. Baicalin can inhibit the development of ferroptosis in ICH. Baicalin is a potential therapeutic drug for ICH treatment. Suppressor . Up regulation . . Suppressor A total of 60 male C57BL/6 mice (10weeks old, 25-28g) were purchased from Guangzhou University of Chinese Medicine Experimental Animal Center (Guangzhou, China). The mice were maintained with enough food and water at 24, 60% relative humidity and 12/12h light/dark cycle. The mice were randomly divided into three groups: sham operation group (Sham), ICH model group (Mod) and baicalin group (Bai) (n = 20/group). Baicalin was suspended in 0.5% carboxymethylcellulose sodium solution. Given the extremely low solubility of baicalin, the concentration of baicalin solution was 0.5 mg/ml. To achieve 20 mg/kg/day dosage, the baicalin solution was administered to the mice in the Bai group by oral route twice at an interval of 1 h within 2 h after ICH injury onset. The remaining two groups received an equal volumes of saline through oral gavage. Since the second day after ICH, mice in the Bai group received 20 mg/kg of baicalin solution while those in the remaining two groups received equal volumes of saline once a day for three consecutive days. REF000374 ICD-11: 8B00 Intracerebral haemorrhage CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00363 Dauricine (Dau) could inhibit ferroptosis of nerve cells and alleviate brain injury after intracerebral hemorrhage by upregulating glutathione peroxidase 4 (GPX4) and glutathione reductase (GSR) co-expression. Therefore, Dau may be an effective drug for inhibiting ferroptosis and treating intracerebral hemorrhage. Suppressor . Up regulation . . Suppressor Adult male C57BL/6 mice weighing 20-28 g were maintained in the specific pathogen-free (SPF) facility to be used in this study. Mice were subjected to a 12-h light/dark cycle at a constant ambient temperature (22 ± 1 ). Mice were randomly assigned into the following five groups based on random numbers generated using SPSS. The sham group(n = 20, of which 20 survived) was subjected to mock surgery (craniotomy without collagenase) and treated with 0.1 mL 0.9% saline. The intracerebral hemorrhage(ICH) group (n = 29, of which 23 survived) was subjected to ICH surgery, then treated with 0.9% saline. The low Dauricine(Dau) group (n = 24, of which 20 survived) was subjected to ICH surgery, then immediately treated with 5 mg/kg Dau via tail vein injection. The medium Dau group (n = 25, of which 22 survived)was subjected to ICH surgery, then treated with 10 mg/kg Dau. The high Dau group (n = 24, of which 22 survived)was subjected to ICH surgery, then immediately treated with 15 mg/kg Dau. REF000492 ICD-11: 8B00 Intracerebral haemorrhage CELL00042 SH-SY5Y Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00407 Iron-dependent oxidative stress (ferroptosis) is a main hallmark of retinal and brain diseases, including hemorrhage. Fucoidans can abrogate the decrease in the protein levels of the antioxidant enzyme GPX4 that is crucial for ferroptosis. Suppressor . Up regulation . . Suppressor . REF000556 ICD-11: 8B00 Brain hemorrhage CELL00072; CELL00485; CELL00042; CELL00549 ARPE-19; OMM-1; SH-SY5Y; HT-22 Fatty acid metabolism (hsa01212); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00746 Single rotenone administration markedly inhibited neuronal viability, promoted iron accumulation, increased malondialdehyde (MDA) contents, decreased total superoxide dismutase (SOD) activity, and downregulated ferroptosis-related proteins RPL8, COX-2, xCT, ASCL4, and GPX4 in primary neurons. Together, our data revealed that intracerebral hemorrhage induced significant mitochondrial dysfunction and that mitochondrial inhibitor rotenone can trigger and enhance neuronal ferroptosis. Inducer . Down regulation . . Suppressor Six-to-eight week old male ICR mice were purchased from the Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China). Herein, a total of 51 mice were randomly divided into 3 groups: (i) sham group (n = 15), (ii) ICH group (n = 18), and (iii) ICH + Rot group (n = 18). All mice were euthanized at 3 d after operation and brain samples were harvested, as per our previously described reports. REF000971 ICD-11: 8B00 Intracerebral haemorrhage CELL10178 Primary cortical neurons Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01596 Treatment of miR-1405p mimics led to decreased COX-2 and ACSL4 expressions, and elevated GPX-4 expressions. circAFF1 can bind miR-1405p to up-regulate GSK-3 expression, thus inhibiting the Wnt/-catenin signaling pathway. And circAFF1 knockdown can suppress ferroptosis of neurons in vitro and therefore attenuate intracerebral hemorrhage (ICH). . . . Up regulation Suppressor Suppressor C57BL/6 J pregnant mice (E15 ~ E16 day) were disinfected with 75% alcohol and then decapitated. The brain was collected and washed in pre-cold D-Hanks solution with the midbrain and hippocampus being removed. The cortex was collected and the meninx was removed. Then the brain tissues were made into 1 mm3 blocks for digestion with 1 ~ 2 mL lysis at 37 for 15 min. The tissues were cultured in high glucose DMEM to terminate the digestion and made into single-cell suspension. The suspension was filtered through a 70 um mesh screen for centrifugation for 5 min with the supernatant being removed. High glucose DMEM was used to re-suspended cells and the concentration of cells was adjusted for cells were seeded into the plate. About 4 h later, the high glucose DMEM was replaced with Neurobasal medium (containing 2% B27). The culture medium was half refreshed every 2 ~ 3 d. The cells were cultured for 8 ~ 10 d before following experiments. REF000803 ICD-11: 8B00 Intracerebral haemorrhage CELL10181 primary neurons Ferroptosis (hsa04216); Wnt signaling pathway (hsa04310) Cell ferroptosis
unique01595 Treatment of miR-1405p mimics led to decreased COX-2 and ACSL4 expressions, and elevated GPX-4 expressions. circAFF1 can bind miR-1405p to up-regulate GSK-3 expression, thus inhibiting the Wnt/-catenin signaling pathway. And circAFF1 knockdown can suppress ferroptosis of neurons in vitro and therefore attenuate intracerebral hemorrhage (ICH). . . . Down regulation Driver Suppressor C57BL/6 J pregnant mice (E15 ~ E16 day) were disinfected with 75% alcohol and then decapitated. The brain was collected and washed in pre-cold D-Hanks solution with the midbrain and hippocampus being removed. The cortex was collected and the meninx was removed. Then the brain tissues were made into 1 mm3 blocks for digestion with 1 ~ 2 mL lysis at 37 for 15 min. The tissues were cultured in high glucose DMEM to terminate the digestion and made into single-cell suspension. The suspension was filtered through a 70 um mesh screen for centrifugation for 5 min with the supernatant being removed. High glucose DMEM was used to re-suspended cells and the concentration of cells was adjusted for cells were seeded into the plate. About 4 h later, the high glucose DMEM was replaced with Neurobasal medium (containing 2% B27). The culture medium was half refreshed every 2 ~ 3 d. The cells were cultured for 8 ~ 10 d before following experiments. REF000803 ICD-11: 8B00 Intracerebral haemorrhage CELL10181 primary neurons Ferroptosis (hsa04216); Wnt signaling pathway (hsa04310) Cell ferroptosis
unique01597 Treatment of miR-1405p mimics led to decreased COX-2 and ACSL4 expressions, and elevated GPX-4 expressions. circAFF1 can bind miR-1405p to up-regulate GSK-3 expression, thus inhibiting the Wnt/-catenin signaling pathway. And circAFF1 knockdown can suppress ferroptosis of neurons in vitro and therefore attenuate intracerebral hemorrhage (ICH). . . . Down regulation Driver Suppressor C57BL/6 J pregnant mice (E15 ~ E16 day) were disinfected with 75% alcohol and then decapitated. The brain was collected and washed in pre-cold D-Hanks solution with the midbrain and hippocampus being removed. The cortex was collected and the meninx was removed. Then the brain tissues were made into 1 mm3 blocks for digestion with 1 ~ 2 mL lysis at 37 for 15 min. The tissues were cultured in high glucose DMEM to terminate the digestion and made into single-cell suspension. The suspension was filtered through a 70 um mesh screen for centrifugation for 5 min with the supernatant being removed. High glucose DMEM was used to re-suspended cells and the concentration of cells was adjusted for cells were seeded into the plate. About 4 h later, the high glucose DMEM was replaced with Neurobasal medium (containing 2% B27). The culture medium was half refreshed every 2 ~ 3 d. The cells were cultured for 8 ~ 10 d before following experiments. REF000803 ICD-11: 8B00 Intracerebral haemorrhage CELL10181 primary neurons Ferroptosis (hsa04216); Wnt signaling pathway (hsa04310) Cell ferroptosis
unique00468 Curcumin in NPs (Cur-NPs) were shown to suppress erastin-induced ferroptosis in HT22 murine hippocampal cells. Cur-NPs effectively regulated the expression levels of HMOX1 and NFE2L2, which indicated that it might inhibit the ROS production through regulating the NRF2/HO-1 pathway. Cur-NPs served as an effective treatment for Intracerebral hemorrhage owing to their ability to inhibit ferroptosis. Suppressor . Up regulation . . Marker/Suppressor Male C57BL/6 mice (8-10 weeks old) were obtained from the Experimental Animal Center of Guangzhou University of Chinese Medicine (Guangzhou, China). Briefly, mice were anesthetized and placed in a prone position with head stabilization in a stereotaxic frame. A dental drill was then utilized to generate a 1 mm burr hole at 2.0 mm to the lateral right of the bregma and 3.5 mm deep of the brain. Next, acute ICH was induced by slowly injecting 0.1U of type IV collagenase into this hole. REF000619 ICD-11: 8B00 Intracerebral haemorrhage CELL00028; CELL00549 MDCK; HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique01072 Acupuncture alleviated ferroptosis and decreased miR-23a-3p expression, as evidenced by the increased NFE2L2 nuclear translocation and expressions of heme oxygenase-1 and glutathione peroxidase 4 and the decreased iron and malondialdehyde contents and reactive oxygen species accumulation. Notably, the binding site of miR-23a-3p existed in NFE2L2. Taken together, acupuncture may alleviate the neuronal cell death, inflammation, and ferroptosis after intracerebral hemorrhage (ICH) by down-regulating miR-23a-3p. . . . Down regulation Driver Marker/Suppressor Male 8-week-old Sprague-Dawley rats were chosen for this study. These animals were randomized to 3, 4, or 5 groups: Design for 3 groups: Sham group, rats underwent sham operation; ICH group, rats underwent ICH operation; ICH + Ac group, rats underwent ICH operation and treated with acupuncture at target acupoints. Design for 4 groups: Sham group; ICH group; ICH + Ac group; ICH + sAc group, rats underwent ICH operation and treated with acupuncture at non-acupoints located 1 cm posterior and parallel to Baihui-penetrating-Qubin needling as previously described. Another design for 4 groups: Sham group; ICH group; ICH + NC group, rats underwent ICH operation and injected with antagomiR-NC; ICH + antagomiR group, rats underwent ICH operation and injected with antagomiR-23a-3p. REF000297 ICD-11: 8B00 Intracerebral haemorrhage CELL10173; CELL10005 Neuronal cell; Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01035 Both apoptosis and ferroptosis, but not necroptosis, were regulated by miR-124/Fpn signaling manipulation. Thus, Fpn upregulation or miR-124 inhibition might be promising therapeutic approachs for intracerebral hemorrhage (ICH). . . . Down regulation Driver Marker/Suppressor Fpn-floxed (Fpnflox/flox) mice were obtained from Dr. N.C. Andrews and transferred into a C57bl/6 background. Mice were treated with a mixture of ketamine (100 mg/kg) and dexmedetomidine (0.5 mg/kg) and immobilized on a stereotaxic apparatus (RWD Life Science Co., Shenzhen). All experimental mice received a total of 20 ul autologous blood injected successively into the caudate nucleus (bregma 0: 0.8 mm anterior, 2 mm left lateral and 3.5 mm deep). REF000250 ICD-11: 8B00 Intracerebral haemorrhage CELL00057; CELL10005 293 T; Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00270 Baicalin significantly increased the mRNA expression of GPX4 and SLC7A11 in the perihematoma brain tissues of intracerebral hemorrhage (ICH) model mice. Baicalin can inhibit the development of ferroptosis in ICH. Baicalin is a potential therapeutic drug for ICH treatment. Suppressor . Up regulation . . Suppressor A total of 60 male C57BL/6 mice (10weeks old, 25-28g) were purchased from Guangzhou University of Chinese Medicine Experimental Animal Center (Guangzhou, China). The mice were maintained with enough food and water at 24, 60% relative humidity and 12/12h light/dark cycle. The mice were randomly divided into three groups: sham operation group (Sham), ICH model group (Mod) and baicalin group (Bai) (n = 20/group). Baicalin was suspended in 0.5% carboxymethylcellulose sodium solution. Given the extremely low solubility of baicalin, the concentration of baicalin solution was 0.5 mg/ml. To achieve 20 mg/kg/day dosage, the baicalin solution was administered to the mice in the Bai group by oral route twice at an interval of 1 h within 2 h after ICH injury onset. The remaining two groups received an equal volumes of saline through oral gavage. Since the second day after ICH, mice in the Bai group received 20 mg/kg of baicalin solution while those in the remaining two groups received equal volumes of saline once a day for three consecutive days. REF000374 ICD-11: 8B00 Intracerebral haemorrhage CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01747 Intracerebral hemorrhage induced significant mitochondrial dysfunction and that mitochondrial inhibitor rotenone can trigger and enhance neuronal ferroptosis. The ferroptosis protein markers ACSL4, COX-2, xCT, RPL8, and GPX4 were significantly upregulated in the hemin group. Rot treatment further enhanced hemin-induced upregulation of ACSL4, COX-2, xCT, RPL8, and GPX4 levels. Inducer Up regulation . . Driver . Six-to-eight week old male ICR mice were purchased from the Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China). All animal procedures have been approved by the Institutional Animal Care and Use Committee of Ruijin hospital, Shanghai Jiao Tong University (Shanghai, China). Efforts were made as much as possible to reduce the number of mice used and to minimize suffering. Herein, a total of 51 mice were randomly divided into 3 groups: (i) sham group (n = 15), (ii) ICH group (n = 18), and (iii) ICH + Rot group (n = 18). To be specific, the current study was divided into two parts of the experimental design. Part 1: to observe the effects of Rot on the mitochondria-related genes, iron levels, MDA levels, SOD activity, hematoma volume, brain edema, and ultrastructural changes of mitochondria, animals were randomly divided into the sham group (n = 9), ICH group (n = 12), and ICH + Rot group (n = 12). All mice were euthanized at 3 d after operation and brain samples were harvested, as per our previously described reports. Part 2: to observe the effect of Rot on neurological deficits following ICH, 18 mice were randomly divided into additional 3 groups (sham group, ICH group, and ICH + Rot group). We evaluated mNSS scores at 1, 3, 7, and 14 days after ICH. We also assessed the memory function with the MWM test at 14 days after ICH. REF000971 ICD-11: 8B00 Intracerebral haemorrhage CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00589 Astragaloside IV (AS-IV) triggered Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of subarachnoid hemorrhage (SAH). The Nrf2 inhibitor ML385 blocked the beneficial effects of neuroprotection. These results consistently suggest that ferroptosis is profoundly implicated in facilitating EBI in SAH, and that AS-IV thwarts the process of ferroptosis in SAH by activating Nrf2/HO-1 pathway. Suppressor . Up regulation . . Suppressor SAH model was constructed by applying endovascular perforation in the rats, according to the protocol introduced in a previous study (Wei et al., 2020), except for slight modifications. Briefly, after performing intraperitoneal anesthesia with 40 mg/kg sodium pentobarbital, the right common carotid, external and internal carotid arteries of the rats were exposed and isolated. The right external carotid artery was ligated, and a 4-0 single-strand nylon thread was used to insert the right internal carotid artery through the stump of the external carotid artery and the bifurcation of the common carotid artery. When resistance is felt when the suture enters the intracranial segment, proceed approximately 3 mm to penetrate internal carotid artery at the bifurcation of middle cerebral artery. The suture was held in this position for 10 s and was then withdrawn. The rats in the Sham group went through an identical procedure, without the suture at the point of resistance. Throughout the experiment, the body temperature of the rats was sustained at around 37 by using a thermal blanket. After the wounds were sutured, the rats were placed in a separate cage and neurological function was closely observed. REF000816 ICD-11: 8B01 Subarachnoid hemorrhage CELL10005 Brain tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00587 Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. Suppressor . Up regulation . . Driver/Suppressor The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group. REF000814 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00586 Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. Suppressor . Down regulation . . Driver The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group. REF000814 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00783 The chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by cerebral ischemia-reperfusion injury. Suppressor . Down regulation . . Driver Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups (200, 100, and 50 mg/kg), and a positive drug group (Ginaton, 21.6 mg/kg). The CIRI model was induced in rats by transient middle cerebral artery occlusion (tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. REF000999 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01659 The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in cerebral ischemia-reperfusion injury model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and ALOX15 expression. . . . Down regulation Suppressor Driver Wild-type SD rats were kept in the Animal Experiment Center of Southeast University. Experimental rats were divided into 4 groups (n = 6 per group). The method of establishing the I/R model was provided in supplementary material. Then, we covered the ligation with gel. In order to fully cover the infarcted area of the heart, we chose to inject about 300 uL of mimics + Gel at 23 mm below the left atrial appendage (about the ligation). In order to prevent excessive irradiation of tissue burns, we selected each irradiation for 2 min to control the body surface temperature for a total of 10 min of irradiation. REF000866 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00030 H9c2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00085 Acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with naotaifang extract involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways. Suppressor . Up regulation . . Suppressor Specific pathogen-free adult male SD rats, (80 ± 5) days old and weighing 220-250 g, were provided by the Hunan Slack Jingda Experimental Animal Co., Ltd (Hunan, China). SD rats were randomly divided into 4 groups with 15 in each group: sham operation group, MCAO group, MCAO + DFP group and MCAO + NTE group. The rats were treated with drugs via oral gavage. According to the average body weight, the MCAO + NTE rats were given NTE at 27 g/kg, and the sham operation and the MCAO rats were given the same volume of saline (2.5 mL) for 7 consecutive days. The MCAO + DFP rats were given DFP at a dose of 125 mg/kg for 3 consecutive days. REF000138 ICD-11: 8B10 Cerebral ischemia CELL10005 Brain tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00585 Baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral ischemia-reperfusion injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. Suppressor . Up regulation . . Suppressor The mice (23-25 g, 8-10 weeks old) were subjected to transientmiddle cerebral artery occlusion (tMCAO) to induce cerebral ischemia as previously described protocol . Briefly, mice were anesthetized with intraperitoneal injection of pentobarbital sodium (60 mg/kg) and subcutaneous injection of meloxicam (10mg/kg) during tMCAO operation. Monofilament with a silicon coating on the tip and a diameter of 0.12 mm (A5-122, Beijing Cinontech Co. Ltd., China) was inserted into the ICA from CCA to occlude the middle cerebral artery (MCA) for 1.5 h. The suture was then removed to restore blood flow for another 22.5 h reperfusion. Sham control mice were subjected to similar surgical operations without MCA occlusion. Specifically, the monofilament was inserted only 5 mm above the carotid bifurcation and withdrew immediately in the Sham group. REF000814 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00549 HT22 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00044 Carvacrol provides protection for hippocampal neurons against cerebral ischemia reperfusion in gerbils by inhibiting ferroptosis through increasing the expression of GPx4. Suppressor . Up regulation . . Suppressor A total of 108 gerbils (male; body weight, 70-90 g; age, 12 to 16 weeks) were used in this study. The gerbils were randomly divided into the following five groups: the vehicle-treated group (sham group),which was given an equal volume of physiological saline; the carvacrol (CAR)-treated group (CAR group); the model group, which underwent the ligation of the bilateral carotid artery for 5 min followed by the loosening of the arterial clamp for reperfusion; the model + CAR-treated groups, which included the CAR-treated group and the model + CAR-treated groups that were treated with CAR (25, 50 and 100 mg/kg/day, i.p.) for 2 consecutive weeks and the model + DFO-treated groups that were treated with DFO (150 mg/kg/day, i.p.) for 2 consecutive weeks as the positive drug group. REF000087 ICD-11: 8B10 Cerebral ischemia CELL10125 Hippocampal neuron Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00662 Our data support a protective role of propofol against ferroptosis as a cause of cell death in mice with cerebral ischemia-reperfusion injury. Propofol protected against cerebral ischemia-reperfusion injury-induced ferroptosis partly by regulating the Nrf2/Gpx4 signaling pathway. Suppressor . Up regulation . . Suppressor Male C57BL/6 mice weighing 20-25 g each were obtained from the Animal Experimental Center of Yisi (Changchun, China). Mice were group-housed in a 12 h light/dark cycle (light between 08:00 and 20:00 h) in a temperature-controlled environment room (23-25 ). Mice had ad libitum access to food and water. All surgical procedures were carried out on animals anesthetized with sodium pentobarbital (30 mg/kg) via intraperitoneal injection. MCAO was achieved by inserting a silicone rubber-coated nylon monofilament into the internal carotid artery through the external carotid artery and temporary ligation of the right common carotid artery with a suture. After 45 min of ischemia, blood flow was restored by removing the filament and the suture, and the mice were allowed to recover for 24 h. REF000890 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00780 The chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by cerebral ischemia-reperfusion injury. Suppressor . Up regulation . . Suppressor Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups (200, 100, and 50 mg/kg), and a positive drug group (Ginaton, 21.6 mg/kg). The CIRI model was induced in rats by transient middle cerebral artery occlusion (tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. REF000999 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00531 Our results indicated the critical role of ferroptosis in cerebral ischemia reperfusion injury. For the first time, we showed that the significant neuroprotective effects of b-Caryophyllene (BCP) in attenuating ischemic stroke injury are correlated with ferroptosis regulation, and its mechanism is associated with activation of the NRF2/HO-1 axis. Suppressor . Up regulation . . Suppressor Rats were anesthetized withisoflurane(2-3% oxygen) and placed in asupine position. And theright common carotid artery (CCA),external carotid artery (ECA), andinternal carotid artery (ICA) were exposed in sequence and separated carefully. Then we ligated the CCA and the ECA in turn, and at the same time, we clamped the internal carotid artery with an arterial clamp. Finally, we inserted a silicone nylon monofilament from the CCA into themiddle cerebral arteryand temporarily fixed it. After 1.5 h ofischemia, the monofilament was taken out and the blood vessels were ligated at theincision. The neck wound was sutured with surgical sutures. Subsequent experiments were performed after 12 h ofreperfusion. In thesham operationrats, except for the absence of the monofilament, the sham operation rats underwent the same surgical procedures as the MCAO/R model rats. REF000737 ICD-11: 8B10-8B11 Cerebral-ischemia reperfusion CELL10176 astrocytes Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01658 The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in cerebral ischemia-reperfusion injury model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and ALOX15 expression. . . . Down regulation Suppressor Driver Wild-type SD rats were kept in the Animal Experiment Center of Southeast University. Experimental rats were divided into 4 groups (n = 6 per group). The method of establishing the I/R model was provided in supplementary material. Then, we covered the ligation with gel. In order to fully cover the infarcted area of the heart, we chose to inject about 300 uL of mimics + Gel at 23 mm below the left atrial appendage (about the ligation). In order to prevent excessive irradiation of tissue burns, we selected each irradiation for 2 min to control the body surface temperature for a total of 10 min of irradiation. REF000866 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00030 H9c2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00583 Edaravone inhibits ferroptosis to attenuate cerebral ischemia-reperfusion injury, probably through the activation of the Nrf2/FPN pathway. Suppressor . Up regulation . . Marker/Suppressor Seventy-three specific-pathogen-free (SPF)grade healthy male Sprague Dawley (SD) rats, weighing 240 ± 20 g, were purchased from Hunan Slake Jingda Experimental Animal Co., Ltd., China (animal certificate number SCXK (Xiang) 2013-0004). The animals were reared in an SPF animal laboratory, and the ambient temperature was maintained at 23 ± 1 . All protocols followed the ARRIVE guidelines in terms of study design, sample size, randomization, outcome measures, data analysis, experimental procedures, and reporting of results. This study was approved by the Animal Ethics Committee of the Hunan University of Chinese Medicine. REF000813 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury . . Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00767 Combining Astragaloside IV and Panax notoginseng saponins attenuates cerebral ischemia-reperfusion injury by activating Nrf2 to inhibit ferroptosis and inflammatory responses. Suppressor . Up regulation . . Marker/Suppressor Rats were randomly assigned to six groups: (1) the sham group, (2) the middle cerebral artery ischaemia-occlusion-reperfusion (MCAO/R) group, (3) the AST IV group, (4) the PNS group, (5) the combination group and (6) the combination + brusatol group. One hundred rats were used in the experiment, of which 9 died during surgery, 10 died of intracranial haemorrhage and brain injury and 63 rats were successfully modelled, for a final success rate of 76.8%. Each group included 9 rats. Behavioural testing was performed on 5 animals in each group. After behavioural testing, 3 rats were used for TTC staining and 6 were used for kit detection and western blot analysis. Existing studies have revealed the toxicological effects of the compatibility of astragalus and P. notoginseng. The dosage and method of AST IV (28 mg/kg) and PNS (80 mg/kg) alone or in combination have been previously determined and were administered intragastrically for three consecutive days (10 ml/kg each time), and the optimal administration times were 50, 26 and 2 h before model establishment.Brusatol (1 mg/kg) was administered intraperitoneally for 1 h prior to modelling. The sham group and the MCAO/R group were given the same amount of saline. REF000989 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00766 Combining Astragaloside IV and Panax notoginseng saponins attenuates cerebral ischemia-reperfusion injury by activating Nrf2 to inhibit ferroptosis and inflammatory responses. Suppressor . Up regulation . . Marker/Suppressor Rats were randomly assigned to six groups: (1) the sham group, (2) the middle cerebral artery ischaemia-occlusion-reperfusion (MCAO/R) group, (3) the AST IV group, (4) the PNS group, (5) the combination group and (6) the combination + brusatol group. One hundred rats were used in the experiment, of which 9 died during surgery, 10 died of intracranial haemorrhage and brain injury and 63 rats were successfully modelled, for a final success rate of 76.8%. Each group included 9 rats. Behavioural testing was performed on 5 animals in each group. After behavioural testing, 3 rats were used for TTC staining and 6 were used for kit detection and western blot analysis. Existing studies have revealed the toxicological effects of the compatibility of astragalus and P. notoginseng. The dosage and method of AST IV (28 mg/kg) and PNS (80 mg/kg) alone or in combination have been previously determined and were administered intragastrically for three consecutive days (10 ml/kg each time), and the optimal administration times were 50, 26 and 2 h before model establishment.Brusatol (1 mg/kg) was administered intraperitoneally for 1 h prior to modelling. The sham group and the MCAO/R group were given the same amount of saline. REF000989 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00661 Our data support a protective role of propofol against ferroptosis as a cause of cell death in mice with cerebral ischemia-reperfusion injury. Propofol protected against cerebral ischemia-reperfusion injury-induced ferroptosis partly by regulating the Nrf2/Gpx4 signaling pathway. Suppressor . Up regulation . . Marker/Suppressor Male C57BL/6 mice weighing 20-25 g each were obtained from the Animal Experimental Center of Yisi (Changchun, China). Mice were group-housed in a 12 h light/dark cycle (light between 08:00 and 20:00 h) in a temperature-controlled environment room (23-25 ). Mice had ad libitum access to food and water. All surgical procedures were carried out on animals anesthetized with sodium pentobarbital (30 mg/kg) via intraperitoneal injection. MCAO was achieved by inserting a silicone rubber-coated nylon monofilament into the internal carotid artery through the external carotid artery and temporary ligation of the right common carotid artery with a suture. After 45 min of ischemia, blood flow was restored by removing the filament and the suture, and the mice were allowed to recover for 24 h. REF000890 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00530 Our results indicated the critical role of ferroptosis in cerebral ischemia reperfusion injury. For the first time, we showed that the significant neuroprotective effects of b-Caryophyllene (BCP) in attenuating ischemic stroke injury are correlated with ferroptosis regulation, and its mechanism is associated with activation of the NRF2/HO-1 axis. Suppressor . Up regulation . . Marker/Suppressor Rats were anesthetized withisoflurane(2-3% oxygen) and placed in asupine position. And theright common carotid artery (CCA),external carotid artery (ECA), andinternal carotid artery (ICA) were exposed in sequence and separated carefully. Then we ligated the CCA and the ECA in turn, and at the same time, we clamped the internal carotid artery with an arterial clamp. Finally, we inserted a silicone nylon monofilament from the CCA into themiddle cerebral arteryand temporarily fixed it. After 1.5 h ofischemia, the monofilament was taken out and the blood vessels were ligated at theincision. The neck wound was sutured with surgical sutures. Subsequent experiments were performed after 12 h ofreperfusion. In thesham operationrats, except for the absence of the monofilament, the sham operation rats underwent the same surgical procedures as the MCAO/R model rats. REF000737 ICD-11: 8B10-8B11 Cerebral-ischemia reperfusion CELL10176 astrocytes Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00782 The chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by cerebral ischemia-reperfusion injury. Suppressor . Down regulation . . Marker Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups (200, 100, and 50 mg/kg), and a positive drug group (Ginaton, 21.6 mg/kg). The CIRI model was induced in rats by transient middle cerebral artery occlusion (tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. REF000999 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00084 Acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with naotaifang extract involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways. Suppressor . Down regulation . . Driver Specific pathogen-free adult male SD rats, (80 ± 5) days old and weighing 220-250 g, were provided by the Hunan Slack Jingda Experimental Animal Co., Ltd (Hunan, China). SD rats were randomly divided into 4 groups with 15 in each group: sham operation group, MCAO group, MCAO + DFP group and MCAO + NTE group. The rats were treated with drugs via oral gavage. According to the average body weight, the MCAO + NTE rats were given NTE at 27 g/kg, and the sham operation and the MCAO rats were given the same volume of saline (2.5 mL) for 7 consecutive days. The MCAO + DFP rats were given DFP at a dose of 125 mg/kg for 3 consecutive days. REF000138 ICD-11: 8B10 Cerebral ischemia CELL10005 Brain tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00584 Edaravone inhibits ferroptosis to attenuate cerebral ischemia-reperfusion injury, probably through the activation of the Nrf2/FPN pathway. Suppressor . Up regulation . . Suppressor Seventy-three specific-pathogen-free (SPF)grade healthy male Sprague Dawley (SD) rats, weighing 240 ± 20 g, were purchased from Hunan Slake Jingda Experimental Animal Co., Ltd., China (animal certificate number SCXK (Xiang) 2013-0004). The animals were reared in an SPF animal laboratory, and the ambient temperature was maintained at 23 ± 1 . All protocols followed the ARRIVE guidelines in terms of study design, sample size, randomization, outcome measures, data analysis, experimental procedures, and reporting of results. This study was approved by the Animal Ethics Committee of the Hunan University of Chinese Medicine. REF000813 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury . . Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00194 Gerbils treated with galangin after ischemia-reperfusion (I/R) injury showed significant improvements in learning and memory. In addition, galangin treatment reduced the levels of lipid peroxide in the brains of gerbils that underwent I/R as well as reduced the amount of cell death and increased the expression of SLC7A11 and glutathione peroxidase 4 (GPX4). Suppressor . Up regulation . . Suppressor Male gerbils weighing 70-90 g (12 weeks) were selected for this study. Gerbils were anesthetized with 7% chloral hydrate (350 mg/kg) and the bilateral common carotid arteries were occluded using artery clips. After 5 min, the clips were removed to restore cerebral blood flow. After the operation, place the gerbil on an electric blanket to keep the gerbil's body temperature. The sham group underwent the same surgical procedure without ligation of carotid arteries and was given an equal volume of physiological saline as in the treated groups. The model + galangin (Jiangsu Yongjian Pharmaceutical Technology, 548-83-4, Purity: >=98% (HPLC)) groups underwent the same procedure as the model group and then were received galangin at 25, 50, or 100 mg/kg/day for two continuous weeks. REF000258 ICD-11: 8B10 Cerebral ischemia CELL10125 Hippocampal neuron Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01561 In the process of cerebral ischemia and reperfusion, the up-regulated miR-27a may induce ferroptosis through inhibiting SLC7A11, thus causing brain tissue damage. . . . Down regulation Driver Suppressor The male Sprague Dawley rats were randomly divided into control group, sham group, middle cerebral artery occlusion/reperfusion model group (MCAO/R group) (according to different ischemia reperfusion time, the model group was divided into the 3, 6, 12 and 24 hours reperfusion groups after 2 hour-ischemia), and vehicle group, agomir-27a group, antagomir-27a group. The Zea-Longa method was used to establish rat MCAO model. REF000770 ICD-11: 8B10 Cerebral ischemia CELL10005 Brain tissues Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00779 The chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by cerebral ischemia-reperfusion injury. Suppressor . Up regulation . . Suppressor Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups (200, 100, and 50 mg/kg), and a positive drug group (Ginaton, 21.6 mg/kg). The CIRI model was induced in rats by transient middle cerebral artery occlusion (tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. REF000999 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00781 The chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by cerebral ischemia-reperfusion injury. Suppressor . Down regulation . . Driver Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups (200, 100, and 50 mg/kg), and a positive drug group (Ginaton, 21.6 mg/kg). The CIRI model was induced in rats by transient middle cerebral artery occlusion (tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. REF000999 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00818 This study revealed the therapeutic potential of berberine on cerebral ischemia-reperfusion injury via inhibiting neuronal ferroptosis, in which upregulated glutathione peroxidase 1 (GPX1) was possibly involved. Suppressor . Up regulation . . Suppressor All animal experiments described in this study were carried out in accordance with the U.K. Animals (Scientific Procedures) Act and were approved by the Experimental Animal Center of Wenzhou Medical University (No. wydw2022-0032). Six-to-eight-weeks old male ICR mice were obtained from Beijing Weitonglihua Experimental Animal Technology Co. Ltd. (Beijing, China). Mice were group-housed in the breeding environment under a 12/12h light/dark cycle, controlled temperature of 20-22 and 50-60% humidity with ad libitum chow and water. All animals were randomized for the research and procedures. REF001038 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL10005 Brain tissues Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01411 Circ-Carm1 was evidently abundant in acute cerebral infarction model cells, and knockdown of circ-Carm1 notably restored cell viability and inhibited ferroptosis in ACI model cells. Mechanistically, circ-Carm1 sponged miR-3098-3p to upregulate ACSL4 expression in ACI model cells to participate in ACI progressionin vitro. . . . Up regulation Driver Driver . REF000657 ICD-11: 8B11 Acute cerebral infarction injury CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00246 Carthamin yellow (CY) treatment inhibited Fe2+ and reactive oxygen species accumulation, and reversed acylCoA synthetase longchain family member 4, transferrin receptor 1, glutathione peroxidase 4 and ferritin heavy chain 1 protein expression levels in the brain. Collectively, the results of the present study demonstrated that CY protected rats against ischemic stroke, which was associated with mitigation of inflammation and ferroptosis. Suppressor . Down regulation . . Driver A total of 32 male Sprague-Dawley rats (aged 6-8 weeks; 250-280 g) were purchased from Shanghai Sipper-BK Lab Animal Co., Ltd. Animals were randomly divided into the following four groups (n = 8 per group): i) Sham; ii) MCAO; iii) CY (20 mg/kg); and iv) CY (40 mg/kg). CY was administered intragastrically to rats once daily for 2 weeks. At 60 min after the last administration, MCAO surgery was performed as previously described. At 24 h post-reperfusion, neurological scores, brain water content and infarct volume were determined. REF000321 ICD-11: 8B11 Ischemic stroke CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique01412 Circ-Carm1 was evidently abundant in acute cerebral infarction model cells, and knockdown of circ-Carm1 notably restored cell viability and inhibited ferroptosis in ACI model cells. Mechanistically, circ-Carm1 sponged miR-3098-3p to upregulate ACSL4 expression in ACI model cells to participate in ACI progressionin vitro. . . . Down regulation Suppressor Driver . REF000657 ICD-11: 8B11 Acute cerebral infarction injury CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01633 ELAVL1 silencing observably facilitated cell viability, GSH content, GPX4 and SLC7A11 expression. ELAVL1 plays a critical role in protecting against ferroptosis-induced cerebral I/R and subsequent brain damage via DNMT3B/PINK1 axis, thus providing a new potential target for ischemic stroke treatment. . . . Down regulation Driver Suppressor Rats were placed on a heating panel after anesthetized with pentobarbital sodium (30 mg/kg). We operated the intraluminal middle cerebral artery occlusion (MCAO) to establish the focal cerebral ischemia. Then 2 h later, we established the reperfusion. In brief, the left internal carotid artery of the rats was isolated. Then the ligation of middle cerebral artery was performed by a 4/0 surgical nylon monofilament to occlude the blood flow. 2 h later, we removed the filament to restore the blood reperfusion for 24 h. REF000847 ICD-11: 8B11 Ischemic stroke CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00323 Kaempferol provides protection from OGD/R-induced ferroptosis, at least in part, by activating Nrf2/SLC7A11/GPX4 signaling pathway. Therefore, pharmacological inhibition of ferroptosis may be an attractive therapeutic target for the treatment of ischemic stroke. Suppressor . Up regulation . . Suppressor . REF000446 ICD-11: 8B11 Ischemic stroke CELL10140 Primary mouse cortical neurons Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00778 Astragaloside IV (AS-IV) administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-, interleukin-1 (IL-1), IL-6, and NF-B, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Suppressor . Up regulation . . Suppressor 1% sodium pentobarbital (40 mg/kg) was administered to the rats intraperitoneally to anesthetize them before placing them in a brain stereotaxic device. An incision was created in the midline of the neck to expose the common internal and external carotid arteries. After ligating and cutting the external carotid artery on the left side, a 3-mm stump was exposed. We then perforated the carotid artery at the bifurcation of the middle and anterior cerebral arteries utilizing an 18-20-mm-long surgical filament (0.26 mm diameter; Beijing Cinontech Co. Ltd., China) was threaded through the external carotid artery stump into the internal carotid artery and left in situ for 120 min. After that, the filament was withdrawn to facilitate reperfusion. Rats in the sham surgery group received the identical procedure as the other rats but without filament insertion. REF000997 ICD-11: 8B11 Ischemic stroke CELL10005 Brain tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01634 miRNA-27-a inhibited Nrf2 in a targeted manner, which also exacerbated the extent of ferroptosis. Therefore, the present study indicated that miRNA-27-a may aggravate brain tissue ferroptosis during ischaemic stroke, potentially by inhibiting Nrf2. . . . Down regulation Driver Marker/Suppressor SPF male Sprague Dawley rats aged 8 weeks were purchased from Beijing HFK Bioscience Co., Ltd. and housed in the Experimental Animal Center of North China University of Science and Technology (licence no. SYXK(Ji)2020-007) at 22 ± 2 with 60 ± 5% humidity, 12 h light/dark cycles, and free access to food and water. The rats were raised adaptively for approximately 7 days before experimental manipulation. The animals were handled according to the National Institute of Healths Guide for the Care and Use of Laboratory Animals (1996) guidelines, and all animal experiments were approved by the Animal Care and Use Committee of North China University of Science and Technology. In addition, all efforts were made to minimize the number of animals used and their suffering. REF000848 ICD-11: 8B11 Ischaemic stroke CELL10005 Brain tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00777 Astragaloside IV (AS-IV) administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-, interleukin-1 (IL-1), IL-6, and NF-B, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Suppressor . Up regulation . . Marker/Suppressor 1% sodium pentobarbital (40 mg/kg) was administered to the rats intraperitoneally to anesthetize them before placing them in a brain stereotaxic device. An incision was created in the midline of the neck to expose the common internal and external carotid arteries. After ligating and cutting the external carotid artery on the left side, a 3-mm stump was exposed. We then perforated the carotid artery at the bifurcation of the middle and anterior cerebral arteries utilizing an 18-20-mm-long surgical filament (0.26 mm diameter; Beijing Cinontech Co. Ltd., China) was threaded through the external carotid artery stump into the internal carotid artery and left in situ for 120 min. After that, the filament was withdrawn to facilitate reperfusion. Rats in the sham surgery group received the identical procedure as the other rats but without filament insertion. REF000997 ICD-11: 8B11 Ischemic stroke CELL10005 Brain tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00322 Kaempferol provides protection from OGD/R-induced ferroptosis, at least in part, by activating Nrf2/SLC7A11/GPX4 signaling pathway. Therefore, pharmacological inhibition of ferroptosis may be an attractive therapeutic target for the treatment of ischemic stroke. Suppressor . Up regulation . . Marker/Suppressor . REF000446 ICD-11: 8B11 Ischemic stroke CELL10140 Primary mouse cortical neurons Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01038 MiR-137 is reported to regulate ferroptosis and to be involved in the neuroprotection against ischemic stroke. MiR-137overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated SH-SY5Y cells. Furthermore, EXsmiR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the MiR-137-COX2/PGE2 signaling pathway. . . . Down regulation Suppressor Marker . REF000253 ICD-11: 8B11 Ischemic stroke CELL00042 SH-SY5Y Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Arachidonic acid metabolism (hsa00590) Cell ferroptosis; Cell apoptosis
unique00321 Kaempferol provides protection from OGD/R-induced ferroptosis, at least in part, by activating Nrf2/SLC7A11/GPX4 signaling pathway. Therefore, pharmacological inhibition of ferroptosis may be an attractive therapeutic target for the treatment of ischemic stroke. Suppressor . Up regulation . . Suppressor . REF000446 ICD-11: 8B11 Ischemic stroke CELL10140 Primary mouse cortical neurons Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01016 PVT1 regulates ferroptosis through miR-214-mediated p53 and TFR1. The discovery of PVT1 and miR-214 as potential targets for I/R also implies that PVT1 and miR-214 play critical roles in ferroptosis, shedding new light on the mechanism of ferroptosis in acute ischemic stroke. . . . Up regulation Driver Marker/Suppressor/Driver . REF000219 ICD-11: 8B11 Acute ischemic stroke CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01014 PVT1 regulates ferroptosis through miR-214-mediated p53 and TFR1. The discovery of PVT1 and miR-214 as potential targets for I/R also implies that PVT1 and miR-214 play critical roles in ferroptosis, shedding new light on the mechanism of ferroptosis in acute ischemic stroke. . . . up regulation Driver Marker/Suppressor/Driver . REF000219 ICD-11: 8B11 Acute ischemic stroke CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01015 PVT1 regulates ferroptosis through miR-214-mediated p53 and TFR1. The discovery of PVT1 and miR-214 as potential targets for I/R also implies that PVT1 and miR-214 play critical roles in ferroptosis, shedding new light on the mechanism of ferroptosis in acute ischemic stroke. . . . Down regulation Suppressor Marker/Suppressor/Driver . REF000219 ICD-11: 8B11 Acute ischemic stroke CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01013 PVT1 regulates ferroptosis through miR-214-mediated p53 and TFR1. The discovery of PVT1 and miR-214 as potential targets for I/R also implies that PVT1 and miR-214 play critical roles in ferroptosis, shedding new light on the mechanism of ferroptosis in acute ischemic stroke. . . . Down regulation Suppressor Marker/Suppressor/Driver . REF000219 ICD-11: 8B11 Acute ischemic stroke CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00244 ADA-409-052 inhibits tert-Butyl hydroperoxide (TBHP)-induced lipid peroxidation (LP) and protects against ferroptotic cell death triggered by glutathione (GSH) depletion or glutathione peroxidase 4 (GPx4) inhibition in neuronal cell lines. Moreover, ADA-409-052 efficiently reduces infarct volume, edema and expression of pro-inflammatory genes in a mouse model of thromboembolic stroke. In addition, ADA-409-052 reduced the expression of stroke-induced Hmox1. Suppressor . Down regulation . . Driver/Suppressor Brain penetration study was carried out by TCG Lifesciences Ltd (Kolkata, India) in male BALB/c mice (6-8 weeks old; 18-20 g, in-house breeding). Mice were housed individually under 12/12 h lightdark cycle with free access to food and water. In two experiments 10 mg/kg or 30 mg/kg of ADA-409-052 (HPLC Purity: 99.7%) dissolved in Tween-80 (0.5%, Merck, Germany) -methylcellulose (Sigma) solution was administered as a single bolus by oral gavage (p.o.). ADA-409-052- or vehicle-administered mice were sacrificed 0.75, 4, and 24 h later (n = 3/group). REF000319 ICD-11: 8B20 Thromboembolic stroke CELL00544; CELL00552; CELL00553 BV2; Neuro-2a; RAW 264.7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00651 Edaravone could significantly reduce A1-42-induced apoptosis of HT22 cells and formation of pro-inflammatory factors TNF-, IL-1 and IL-6, prevent the activation of TLR4/NF-kB /NLRP3 signaling pathway, and inhibit ferroptosis and lipid peroxidation. Taken together, EDA contributes to inhibiting neuroinflammatory injury and ferroptosis in A 1-42-induced HT22 cells, and thus may be a potential candidate for the treatment of AD. Suppressor Down regulation . . Driver . . REF000879 ICD-11: 8C1Z Neuroinflammation CELL00549 HT22 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01485 An intrathecal injection of SIRT2 overexpressed recombinant adenovirus, which upregulated the expression of SIRT2, attenuated mechanical allodynia, enhanced the level of FPN1, inhibited intracellular iron accumulation, and reduced oxidant stress levels, thereby reversing the changes to ACSL4 and GPX4 expression in the SNI rats. This evidence suggests that SIRT2-targeted therapeutics may help relieve the symptoms of chronic neuropathic pain (NP). . . . Up regulation Suppressor Marker/Suppressor About 70 adult male Sprague-Dawley rats weighing 200-250 g were used in the animal model. Rats were anesthetized with 5% isoflurane by a small animal anesthesia machine and maintained with 2-3% isoflurane. The rats were placed in a left decubitus position; approximately 1 cm below the right iliac bone, the three branches of the sciatic nerve were exposed: the tibial nerve, common peroneal nerve, and sural nerve. REF000713 ICD-11: 8E43 Neuropathic pain . . Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00312 N2L recovered glutathione peroxidase 4 (GPX4) expression and blocked the increase of Cyclooxygenase-2 (cox-2) and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein expressions. Moreover, N2L also significantly prevented Ferritin Heavy Chain 1 (FTH1) from downregulation and maintained iron homeostasis. And N2L could be a ferroptosis inhibitor for the therapy of ferroptosis-related neurodegenerative diseases, such as Alzheimer's disease. Suppressor . Down regulation . . Driver . REF000439 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010) Cell ferroptosis
unique00593 Sertaconazole is the most potent ACSL4 inhibitor identified. In addition, sertaconazole significantly reduced lipid peroxidation and ferroptosis in human differentiated dopaminergic neurons (Lund human mesencephalic LUHMES cells), demonstrating that it is a valuable chemical tool for further investigating the role of ACSL4 in nervous system disease. Suppressor . Down regulation . . Driver . REF000824 ICD-11: 8E7Z Nervous system disease CELL00504 LUHMES Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00313 N2L recovered glutathione peroxidase 4 (GPX4) expression and blocked the increase of Cyclooxygenase-2 (cox-2) and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein expressions. Moreover, N2L also significantly prevented Ferritin Heavy Chain 1 (FTH1) from downregulation and maintained iron homeostasis. And N2L could be a ferroptosis inhibitor for the therapy of ferroptosis-related neurodegenerative diseases, such as Alzheimer's disease. Suppressor . Up regulation . . Marker/Suppressor . REF000439 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010) Cell ferroptosis
unique00333 Moracin N was a good ferroptosis inhibitor in Neurodegenerative diseases. The neuroprotective mechanisms of moracin N included inhibition of glutathione depletion, glutathione peroxidase 4 (GPx4) inactivation, reactive oxygen species (ROS) overproduction and iron accumulation, as well as improvement of intracellular antioxidant enzyme activities. Suppressor . Up regulation . . Suppressor . REF000456 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00057 Gastrodin (GAS) is a component of Gastrodia elata Blume, with strong antioxidant activity in neurodegenerative diseases. GAS increased the nuclear translocation of Nrf2, up-regulated the downstream HO-1 protein expression in HT-22 cells following treatment with glutamate. Suppressor . Up regulation . . Driver/Suppressor . REF000107 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00337 Ajudecunoid C effectively prevented ferroptosis through scavenging free radical and activating NRF2-antioxidant response elements (AREs) pathway. This study reveals that ADC, as a new ferroptosis inhibitor, is a promising lead compound for the development of drugs against ferroptosis-related neurological diseases. Suppressor . Up regulation . . Marker/Suppressor . REF000463 ICD-11: 8E7Z Nervous system disease CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00056 Gastrodin (GAS) is a component of Gastrodia elata Blume, with strong antioxidant activity in neurodegenerative diseases. GAS increased the nuclear translocation of Nrf2, up-regulated the downstream HO-1 protein expression in HT-22 cells following treatment with glutamate. Suppressor . Up regulation . . Marker/Suppressor . REF000107 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00311 N2L recovered glutathione peroxidase 4 (GPX4) expression and blocked the increase of Cyclooxygenase-2 (cox-2) and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein expressions. Moreover, N2L also significantly prevented Ferritin Heavy Chain 1 (FTH1) from downregulation and maintained iron homeostasis. And N2L could be a ferroptosis inhibitor for the therapy of ferroptosis-related neurodegenerative diseases, such as Alzheimer's disease. Suppressor . Down regulation . . Marker . REF000439 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010) Cell ferroptosis
unique00073 Cumene hydroperoxide strongly induces lipid peroxidation. Moreover, this can be suppressed by Fer-1 as well as iron chelators such as DFO (not shown). Increased oxidative stress drives the loss of PRDX1 expression and renders CEnCs susceptible to lipid peroxidation in Fuchs' endothelial corneal dystrophy. Inducer Down regulation . . Suppressor . . REF000122 ICD-11: 9A70 Fuchs endothelial corneal dystrophy CELL10096; CELL10056; CELL00095 hCEnCs; B4G12-CEnC; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01615 ZFAS1 may act as a competing endogenous RNA by competitively binding with microRNA-7-5p (miR-7-5p) and modulating the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4), which is now identified as a classic driver gene of ferroptosis process. In conclusion, our results demonstrate that HG-induced ZFAS1 elevation activates ferroptosis in hRECs and the ZFAS1/ miR-7-5p/ACSL4 axis may serve as a therapeutic target for endothelial dysfunction in diabetic retinopathy. . . . Down regulation Suppressor Driver For in vivo experiments, the eyes in each group (n = 6) were enucleated carefully and processed for indirect immunofluorescence in whole-mount or cross-section as previously described. For cryosections, the eyes (n = 3 retinae from 3 mice) were fixed in 4% PFA at room temperature for 15 min. The frozen samples were then sliced transversely (6 um) at -20. For retinal flat-mounts, the eyes (n = 3 eyes from 3 mice) were fixed in 4% PFA at room temperature for 15 min, and the retinae were dissected out as cups. Both cryosections and retinal cups were blocked with PBS containing 0.5% Triton-X100 and 5% BSA at 4 overnight and included with the anti-CD31 and anti-GPX4 (1:100, ab125066, Abcam) primary antibodies. REF000827 ICD-11: 9B71.0 Diabetic retinopathy CELL10034 hRECs Ferroptosis (hsa04216) Cell ferroptosis
unique01614 ZFAS1 may act as a competing endogenous RNA by competitively binding with microRNA-7-5p (miR-7-5p) and modulating the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4), which is now identified as a classic driver gene of ferroptosis process. In conclusion, our results demonstrate that HG-induced ZFAS1 elevation activates ferroptosis in hRECs and the ZFAS1/miR-7-5p/ACSL4 axis may serve as a therapeutic target for endothelial dysfunction in diabetic retinopathy. . . . Up regulation Driver Driver For in vivo experiments, the eyes in each group (n = 6) were enucleated carefully and processed for indirect immunofluorescence in whole-mount or cross-section as previously described. For cryosections, the eyes (n = 3 retinae from 3 mice) were fixed in 4% PFA at room temperature for 15 min. The frozen samples were then sliced transversely (6 um) at -20. For retinal flat-mounts, the eyes (n = 3 eyes from 3 mice) were fixed in 4% PFA at room temperature for 15 min, and the retinae were dissected out as cups. Both cryosections and retinal cups were blocked with PBS containing 0.5% Triton-X100 and 5% BSA at 4 overnight and included with the anti-CD31 and anti-GPX4 (1:100, ab125066, Abcam) primary antibodies. REF000827 ICD-11: 9B71.0 Diabetic retinopathy CELL10034 hRECs Ferroptosis (hsa04216) Cell ferroptosis
unique01247 TRIM46 interacted with GPX4, an important enzyme that suppresses ferroptosis, and promoted GPX4 ubiquitination. The role of TRIM46 in GPX4 ubiquitination should inspire the future development of new therapies against diabetic retinopathy (DR). . . . Down regulation Driver Suppressor . REF000496 ICD-11: 9B71.0 Diabetic retinopathy CELL10098 HRCECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01343 Downregulation of circ-PSEN1 ameliorates HG-induced ferroptosis in ARPE19 cells via miR-200b-3p/CFL2 and may be a novel therapeutic target for diabetic retinopathy. Enhancement of CFL2 suppressed the mRNA and protein expression of GPX4 and SLC7A11. However, TFR1 expression was promoted. . . . Down regulation Driver Suppressor . REF000608 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE19 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01344 Downregulation of circ-PSEN1 ameliorates HG-induced ferroptosis in ARPE19 cells via miR-200b-3p/CFL2 and may be a novel therapeutic target for diabetic retinopathy. Enhancement of CFL2 suppressed the mRNA and protein expression of GPX4 and SLC7A11. However, TFR1 expression was promoted. . . . Up regulation Suppressor Suppressor . REF000608 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE19 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01345 Downregulation of circ-PSEN1 ameliorates HG-induced ferroptosis in ARPE19 cells via miR-200b-3p/ CFL2 and may be a novel therapeutic target for diabetic retinopathy. Enhancement of CFL2 suppressed the mRNA and protein expression of GPX4 and SLC7A11. However, TFR1 expression was promoted. . . . Down regulation Driver Suppressor . REF000608 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE19 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01458 High glucose upregulated miR-338-3p to cause SLC1A5-deficiency in RPE cells, resulting in oxidative stress mediated cell ferroptosis, which further caused RPE cell death and aggravate diabetic retinopathy (DR) progression. . . . Down regulation Suppressor Driver . REF000691 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE-19 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01346 Downregulation of circ-PSEN1 ameliorates HG-induced ferroptosis in ARPE19 cells via miR-200b-3p/CFL2 and may be a novel therapeutic target for diabetic retinopathy. Enhancement of CFL2 suppressed the mRNA and protein expression of GPX4 and SLC7A11. However, TFR1 expression was promoted. . . . Up regulation Driver Marker/Suppressor/Driver . REF000608 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE19 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01347 Downregulation of circ-PSEN1 ameliorates HG-induced ferroptosis in ARPE19 cells via miR-200b-3p/CFL2 and may be a novel therapeutic target for diabetic retinopathy. Enhancement of CFL2 suppressed the mRNA and protein expression of GPX4 and SLC7A11. However, TFR1 expression was promoted. . . . Down regulation Suppressor Marker/Suppressor/Driver . REF000608 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE19 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01348 Downregulation of circ-PSEN1 ameliorates HG-induced ferroptosis in ARPE19 cells via miR-200b-3p/ CFL2 and may be a novel therapeutic target for diabetic retinopathy. Enhancement of CFL2 suppressed the mRNA and protein expression of GPX4 and SLC7A11. However, TFR1 expression was promoted. . . . Up regulation Driver Marker/Suppressor/Driver . REF000608 ICD-11: 9B71.0 Diabetic retinopathy CELL00072 ARPE19 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00279 Sodium iodate-induced oxidative stress model has been identified to be heme oxygenase-1 (HO-1)-regulated ferroptosis, which is controlled by the Nrf2-SLC7A11-HO-1 hierarchy. These findings highlight that targeting HO-1-mediated RPE ferroptosis could serve as an effectively retinal-protective strategy for retinal degenerative diseases prevention, including age-related macular degeneration (AMD). Inducer . Down regulation . . Driver/Suppressor In this study, sixteen-week-old male C57BL/6 mice were used and housed in a standard laboratory environment. Forin vivostudies, left eyes were pretreated with a single intravitreal injection of DMSO (1 uL) or 1X PBS (1 uL), and right eyes were pretreated with Fer-1 (30 uM, a single intravitreal injection, 1 uL), DFO (100 uM, a single intravitreal injection, 1 uL), or ZnPP (50 mg/kg, intraperitoneal injection once a week). 15 min later, injection of NaIO3(35 mg/kg, a single injectionviatail vein), or 1X PBS (a single injectionviatail vein, 75 uL) has been performed. After 2 weeks, mice were used for subsequent experiments. REF000390 ICD-11: 9B75 Age-related macular degeneration CELL00072 ARPE-19 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00806 Expression of mitochondrial GPX4 but no other forms of GPX4 was decreased after artesunate treatment and that mitochondrial GPX4 overexpression rescued artesunate-induced lipid peroxidation and ferroptosis. Other cellular ferroptosis defense mechanisms, including cellular FSP1 and Nrf2, were also inhibited by artesunate. In conclusion, our study demonstrated that artesunate protects against fibrosis through abrogation of fibroblast activation and induction of mitochondria-dependent ferroptosis in ocular fibrosis, which may offer a potential treatment for ocular fibrosis. Inducer . Down regulation . . Marker/Suppressor . REF001023 ICD-11: 9C82.2 Ocular fibrosis CELL10032 Human ocular fibroblasts (OFs) Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique00805 Expression of mitochondrial GPX4 but no other forms of GPX4 was decreased after artesunate treatment and that mitochondrial GPX4 overexpression rescued artesunate-induced lipid peroxidation and ferroptosis. Other cellular ferroptosis defense mechanisms, including cellular FSP1 and Nrf2, were also inhibited by artesunate. In conclusion, our study demonstrated that artesunate protects against fibrosis through abrogation of fibroblast activation and induction of mitochondria-dependent ferroptosis in ocular fibrosis, which may offer a potential treatment for ocular fibrosis. Inducer . Down regulation . . Suppressor . REF001023 ICD-11: 9C82.2 Ocular fibrosis CELL10032 Human ocular fibroblasts (OFs) Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique00086 The study measured iron levels in a simulated ageing model established by the addition of d-galactose (d-gal). These changes were accompanied by upregulation of iron regulatory protein 2 (IRP-2), which led to an increase in transferrin receptor 1 (TfR-1), thus increasing iron entry into cells and potentially leading to ferroptosis. Relieving ferroptosis might be a new intervention strategy for age-related hearing loss. Inducer . Up regulation . . Driver A total of 150 male Sprague-Dawley rats were obtained from the Experimental Animal Centre of Hubei Province. After deep anaesthesia, we placed each rat on an electric blanket to maintain its body temperature. We placed the positive electrode under the skin of the vertex, the negative electrode into the measured ear and the ground electrode into the other ear. We used a Tucker-Davis Technologies System (RZ6; Tucker-Davis Tech. Inc., Alachua, FL, USA) to record the responses of the rats to sounds of different frequencies as previously described. REF000140 ICD-11: AB54 Age-related hearing loss CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00821 Aortic GPX4 (a core regulator of ferroptosis) significantly downregulated association with VSMC novel phenotype elevation in SHR rats and hypertension patients. The ferroptosis inhibitor ferrostatin-1 (Fer-1) administration blocked HHP-induced VSMC inflammatory (CXCL2 expression) and endothelial function inhibitory ( AKR1C2 expression) phenotyping switch association with elevation in the GPX4 expression, reduction in the reactive oxygen species (ROS), and lipid peroxidation production. . . . Up regulation Suppressor Suppressor Aortic smooth muscle cells were isolated from wild-type male 6-8-week and CSE-knockout mice. Mice were sacrificed by decapitation, followed by separating the aorta via removing the fatty tissue and vascular adventitia. Then, the mouse aorta was cut into pieces and allowed for digestion for 8 h in the DMEM containing collagenase type 1. The obtained VSMCs were centrifuged at 300 xg for 5 min, and the pellet was resuspended in the DMEM supplemented with 10% FBS, 2 mM l-glutamine, and 100 U/mL penicillin/streptomycin. The medium was replaced every 2 days. REF000003 ICD-11: BA00 Hypertension CELL00143 HASMCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01504 Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. . . . Up regulation Driver Driver Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection). REF000724 ICD-11: BA41 Myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01505 Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. . . . Down regulation Suppressor Driver Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection). REF000724 ICD-11: BA41 Myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00942 BACH1 accelerates ferroptosis by suppressing labile iron metabolism. And ferritin genes (Fth1 and Ftl1) and the ferroportin gene (Slc40a1) were dramatically up-regulated in Bach1-/- MEFs. BACH1 controls the threshold of ferroptosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction. . . . Down regulation Driver Marker/Suppressor The generation of Bach1-/-mice on the C57BL/6J background was described previously. Mice 13 weeks of age were analyzed for models of AMI. The mice were subjected to ligation of the proximal LAD to induce AMI. They were randomly assigned to sham or AMI, DMSO, or DFX groups. REF000113 ICD-11: BA41 Myocardial infarction CELL10119 MEFs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique00943 BACH1 accelerates ferroptosis by suppressing labile iron metabolism. And ferritin genes (Fth1 and Ftl1) and the ferroportin gene (Slc40a1) were dramatically up-regulated in Bach1-/- MEFs. BACH1 controls the threshold of ferroptosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction. . . . Down regulation Driver Suppressor The generation of Bach1-/-mice on the C57BL/6J background was described previously. Mice 13 weeks of age were analyzed for models of AMI. The mice were subjected to ligation of the proximal LAD to induce AMI. They were randomly assigned to sham or AMI, DMSO, or DFX groups. REF000113 ICD-11: BA41 Myocardial infarction CELL10119 MEFs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique01185 MiR-190a-5p negatively regulate ferroptosis via directly targeting GLS2 in rat cardiomyocyte H9c2 cells. Forced expression of miR-190a-5p inhibited GLS2, resulting in downregulation of ROS, MDA and Fe2+accumulation. In summary, miR-190a-5p plays an essential role in regulation of ferroptosis of cardiomyocytes and suggest a potential therapeutic target for myocardial infarction. . . . Down regulation Suppressor Driver . REF000427 ICD-11: BA41 Myocardial infarction CELL00030; CELL00057 H9C2; HEK-293T Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01213 GPX4 was the direct target of miR-15a-5p by luciferase reporter assay. Mechanistically, silencing transcription factor early growth response-1 (Egr-1) inhibited the level of miR-15a-5p, increased the protein expression of GPX4, accompanied by reduced ferroptosis and alleviated myocardial injury. These results provide a novel signaling pathway during the progression of acute myocardial infarction, namely Egr-1/miR-15a-5p/GPX4/ferroptosis. . . . Down regulation Driver Suppressor The male C57BL/6 mice (20-25 g, 10-week-old) were purchased from the Experimental Animal Center of Harbin Medical University (Harbin, China). Mice were anaesthetized with pentobarbital sodium (30 mg/kg, Sigma-Aldrich, St. Louis, USA) by intraperitoneal injection. The animals were fixed on the operating table in supine position, and the chest were sterilized and opened by blunt separation at the left 4th intercosal space. In the model group, the left anterior descending artery (LAD) was ligated with 7/0 silk suture for 3 days. REF000472 ICD-11: BA41 Acute myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01214 GPX4 was the direct target of miR-15a-5p by luciferase reporter assay. Mechanistically, silencing transcription factor early growth response-1 ( Egr-1) inhibited the level of miR-15a-5p, increased the protein expression of GPX4, accompanied by reduced ferroptosis and alleviated myocardial injury. These results provide a novel signaling pathway during the progression of acute myocardial infarction, namely Egr-1/miR-15a-5p/GPX4/ferroptosis. . . . Down regulation Driver Suppressor The male C57BL/6 mice (20-25 g, 10-week-old) were purchased from the Experimental Animal Center of Harbin Medical University (Harbin, China). Mice were anaesthetized with pentobarbital sodium (30 mg/kg, Sigma-Aldrich, St. Louis, USA) by intraperitoneal injection. The animals were fixed on the operating table in supine position, and the chest were sterilized and opened by blunt separation at the left 4th intercosal space. In the model group, the left anterior descending artery (LAD) was ligated with 7/0 silk suture for 3 days. REF000472 ICD-11: BA41 Acute myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00394 Treatment with ferroptosis inhibitor, UAMC-3203 or/and DFO, reduced severity of myocardial dysfunction, and we further found that GPX4 and 4-HNE were significantly changed after CPR. Therefore, UAMC-3203 and DFO alleviated myocardial dysfunction via inhibiting ferroptosis, which could be a novel possible target for post-resuscitation myocardial dysfunction (PRMD) treatment. Suppressor . Up regulation . . Suppressor Male Sprague-Dawley rats (450 g-550 g) were purchased from Envigo (Frederick, Md). Animals were kept under standard conditions with a 12/12-h day/night cycle and received food and waterad libitum. Following induction with inhaling low flow CO2 for 30 s, animals were anesthetized by intraperitoneal injection of pentobarbital (45 mg/kg). Additional doses (10 mg/kg) were administered as needed based on tail pinch/withdrawal reflex to maintain anesthesia. REF000532 ICD-11: BA41 Post-resuscitation myocardial dysfunction CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01502 Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. . . . Up regulation Driver Marker Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection). REF000724 ICD-11: BA41 Myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01503 Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and the miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Over-expression of lncRNA Gm47283 significantly increased the expression of Ptgs2 and Alox15 and repressed the expression of Gpx4. . . . Down regulation Suppressor Marker Male mice were used in this research. The mice were housed in a colony room at a controlled temperature (22) and humidity, under a 12-h light/dark cycle, and with food and water freely available. All surgical procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. In brief, the mice were anesthetized by 3% pentobarbital sodium and then ligated the anterior descending branch of the left coronary artery (LAD) for 48 h to establish the in vivo MI models. The sham group mice were opened the chest bur not ligated with LAD. The mice were randomly divided into three groups as follows: (1) the sham group, which underwent sham operation and received vehicle (PBS, caudal vein injection); (2) the model group, which was subjected to LAD and received vehicle (PBS, caudal vein injection); and (3) the siRNA group, which were subjected to LAD and treated with siRNA of lncRNA Gm47283 (30 nM siRNA dose per mice every day for one week, caudal vein injection). REF000724 ICD-11: BA41 Myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00992 The exosome of MSCs derived from human umbilical cord blood (HUCB-MSC) has been reported to have cardioprotective effects on mouse models of acute myocardial infarction (AMI) and cardiomyocyte hypoxia injury. HUCB-MSCs-exosomes may suppress DMT1 expression by miR-23a-3p to inhibit ferroptosis and attenuate myocardial injury. . . . Down regulation Suppressor Driver A total of 72 C57BL/6J mice (six animals per group) were obtained from the Shanghai Laboratory Animals Center. The mouse model of AMI was performed by permanent ligation of the LAD coronary artery. PBS or exosomes (5 ug, in 20 ul PBS) was injected into the border zone of infarcted heart at three sites. REF000189 ICD-11: BA41 Acute myocardial infarction CELL10102 HUCB-MSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00944 BACH1 accelerates ferroptosis by suppressing labile iron metabolism. And ferritin genes (Fth1 and Ftl1) and the ferroportin gene (Slc40a1) were dramatically up-regulated in Bach1-/- MEFs. BACH1 controls the threshold of ferroptosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction. . . . Down regulation Driver Marker/Suppressor The generation of Bach1-/-mice on the C57BL/6J background was described previously. Mice 13 weeks of age were analyzed for models of AMI. The mice were subjected to ligation of the proximal LAD to induce AMI. They were randomly assigned to sham or AMI, DMSO, or DFX groups. REF000113 ICD-11: BA41 Myocardial infarction CELL10119 MEFs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique01274 lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and Diabetic cardiomyopathy development. Inhibition of ZFAS1 restored the expression of FTH1, reduced the expression of 4HNE, rescued the expression of GPX4 and inhibited the expression of apoptosisrelated genes. . . . Down regulation Driver Marker/Suppressor To simulate the animal model of diabetic cardiomyopathy, male db/+ mice and db/db mice (age, 7 weeks, weight, 24 g) were fed a normal diet for 4 weeks and kept at 24 under a 14-h light/8-h dark cycle. The animals were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). Diabetic mice were intracoronarily administered equal volumes (80 ul) of adenoviruses Ad-ZFAS1, Ad-sh-ZFAS1, Ad-CCND2, Ad-sh-CCND2 or Ad-NC.33 miR-150-5p mimics and mimic control (NC) were injected into the tail vein of mice (50 ug/kg) every 15 days for 12 weeks. Db/db mice were treated with or without ferrostatin-1 (Fer-1, ferroptosis inhibitor; Sigma-Aldrich, 5 mg/kg) for an additional 12 weeks. REF000526 ICD-11: BC43.7 Diabetic cardiomyopathy CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01709 Berberine (Ber) downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against imatinib mesylate-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis. Suppressor . Up regulation . . Marker All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. REF000931 ICD-11: BC43.20 Cardiotoxicity induced by IMA CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01275 lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and Diabetic cardiomyopathy development. Inhibition of ZFAS1 restored the expression of FTH1, reduced the expression of 4HNE, rescued the expression of GPX4 and inhibited the expression of apoptosisrelated genes. . . . Up regulation Suppressor Marker/Suppressor To simulate the animal model of diabetic cardiomyopathy, male db/+ mice and db/db mice (age, 7 weeks, weight, 24 g) were fed a normal diet for 4 weeks and kept at 24 under a 14-h light/8-h dark cycle. The animals were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). Diabetic mice were intracoronarily administered equal volumes (80 ul) of adenoviruses Ad-ZFAS1, Ad-sh-ZFAS1, Ad-CCND2, Ad-sh-CCND2 or Ad-NC.33 miR-150-5p mimics and mimic control (NC) were injected into the tail vein of mice (50 ug/kg) every 15 days for 12 weeks. Db/db mice were treated with or without ferrostatin-1 (Fer-1, ferroptosis inhibitor; Sigma-Aldrich, 5 mg/kg) for an additional 12 weeks. REF000526 ICD-11: BC43.7 Diabetic cardiomyopathy CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01276 lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and Diabetic cardiomyopathy development. Inhibition of ZFAS1 restored the expression of FTH1, reduced the expression of 4HNE, rescued the expression of GPX4 and inhibited the expression of apoptosisrelated genes. . . . Up regulation Suppressor Marker/Suppressor To simulate the animal model of diabetic cardiomyopathy, male db/+ mice and db/db mice (age, 7 weeks, weight, 24 g) were fed a normal diet for 4 weeks and kept at 24 under a 14-h light/8-h dark cycle. The animals were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). Diabetic mice were intracoronarily administered equal volumes (80 ul) of adenoviruses Ad-ZFAS1, Ad-sh-ZFAS1, Ad-CCND2, Ad-sh-CCND2 or Ad-NC.33 miR-150-5p mimics and mimic control (NC) were injected into the tail vein of mice (50 ug/kg) every 15 days for 12 weeks. Db/db mice were treated with or without ferrostatin-1 (Fer-1, ferroptosis inhibitor; Sigma-Aldrich, 5 mg/kg) for an additional 12 weeks. REF000526 ICD-11: BC43.7 Diabetic cardiomyopathy CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01271 lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and Diabetic cardiomyopathy development. Inhibition of ZFAS1 restored the expression of FTH1, reduced the expression of 4HNE, rescued the expression of GPX4 and inhibited the expression of apoptosisrelated genes. . . . Down regulation Driver Suppressor To simulate the animal model of diabetic cardiomyopathy, male db/+ mice and db/db mice (age, 7 weeks, weight, 24 g) were fed a normal diet for 4 weeks and kept at 24 under a 14-h light/8-h dark cycle. The animals were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). Diabetic mice were intracoronarily administered equal volumes (80 ul) of adenoviruses Ad-ZFAS1, Ad-sh-ZFAS1, Ad-CCND2, Ad-sh-CCND2 or Ad-NC.33 miR-150-5p mimics and mimic control (NC) were injected into the tail vein of mice (50 ug/kg) every 15 days for 12 weeks. Db/db mice were treated with or without ferrostatin-1 (Fer-1, ferroptosis inhibitor; Sigma-Aldrich, 5 mg/kg) for an additional 12 weeks. REF000526 ICD-11: BC43.7 Diabetic cardiomyopathy CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01708 Berberine (Ber) downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against imatinib mesylate-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis. Suppressor . Up regulation . . Suppressor All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. REF000931 ICD-11: BC43.20 Cardiotoxicity induced by IMA CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00643 Canagliflozin (Cana) promotes upregulation of SLC7A11 and downregulation of TfR1 and FTN-H, which protect the cardiomyocytes from ferroptosis. These finding suggests that Cana inhibit ferroptosis by balancing cardiac iron homeostasis and promoting the system Xc/GSH/GPX4 axis in diabetic cardiomyopathy. Suppressor . Up regulation . . Suppressor Male C57BL/6J mice aged 6-8 weeks with weights of 18-20 g were obtained from the Slack Laboratory Animal Co., Ltd. (Shanghai, China). Mice were allowed to acclimatize in the laboratory environment for 1 week before the beginning of the experiment. DCM model establishment: The mice were given a single intraperitoneal injection of 150 mg/kg 1% streptozotocin (STZ, V900890, Sigma, USA, dissolved in 0.1 mol/L sodium citrate buffer, pH = 4.4 - 4.6). Mouse blood from the tail vein was collected in each group of the model mice and tested by glucose meter (Accu-Chek Performa test strips, Roche, Accu-Chek Performa Combo, Roche, USA) on day 3, 5 and 7 after injection. REF000875 ICD-11: BC43.7 Diabetic cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00563 Curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy. Suppressor . Up regulation . . Suppressor Two-month-old male New Zealand rabbits purchased from the Medical Experimental Animal Center of Bengbu Medical College were used as experimental subjects. Streptozotocin was dissolved in sterile saline and intraperitoneally injected into the rabbits at a dose of 80 mg/kg. The rabbits were allowed to eat freely after receiving the injection. The fasting blood glucose levels of the rabbits were monitored regularly. The diabetic rabbit model was considered successfully established when the fasting blood glucose level was measured as 11 mmol/L twice or 14 mmol/L once. Following successful modelling, grouping was performed as follows: blank control group (Con-Group), diabetic rabbit group (DM-Group), diabetic rabbit + every other day curcumin administration group (Qod-Group), and diabetic rabbit + daily administration group (Qd-Group). REF000792 ICD-11: BC43.7 Diabetic cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00114 Doxorubicin (DOX) downregulated glutathione peroxidase 4 (GPx4) and induced excessive lipid peroxidation through DOX-Fe2+ complex in mitochondria, leading to mitochondria-dependent ferroptosis. The findings suggest that mitochondria-dependent ferroptosis plays a key role in progression of doxorubicin-induced cardiomyopathy (DIC) and that ferroptosis is the major form of regulated cell death in DOX cardiotoxicity. Inducer . Down regulation . . Suppressor Male C57BL/6J mice were housed in a temperature- and humidity-controlled room, fed a commercial diet (CRF-1; Oriental Yeast Co. Ltd.), and given free access to water. GPx4 Tg mice and GPx4 hetKO mice were produced as previously described. In these gene-manipulated mice, GPx4 was systemically overexpressed or absent, respectively. These strains were backcrossed with C57BL/6J mice in our laboratory. The DIC model was reproduced as previously reported, with some modification. Briefly, DOX (6 mg/kg, body weight) was administered to mice via tail vein at days 0, 2, and 4. REF000170 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL10051 Cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00808 Liquiritin can protect the doxorubicin-induce mice's cardiotoxicity, and its beneficial effect is related to the reduction of ferroptosis through a mechanism involving the regulation of the SLC7A11/GPX4 pathway. Suppressor . Up regulation . . Suppressor The set of animal experiments was designed to evaluate the effectiveness of liquiritin on doxorubicin-induced cardiotoxicity as were as ferroptosis were explored. Mice were randomly divided into 5 groups: (1) the control group; (2) doxorubicin group; (3) the doxorubicin plus liquiritin group (20 mg/kg); (4) the doxorubicin plus liquiritin group (40 mg/kg); (5) the doxorubicin plus liquiritin group (80 mg/kg) (Han et al.2022; Mou et al.2021). The control group and doxorubicin group were given equal volume of 0.5% sodium carboxymethylcellulose; the doxorubicin plus liquiritin groups were given different doses of liquiritin (0.5%) sodium carboxymethylcellulose co-suspension) by intragastric administration 7 days in advance once a daily. On day 8, groups (2), (3), (4), and (5) were given a single intraperitoneal injection of 15 mg/kg of DOX to establish a model of doxorubicin-induced cardiotoxicity; and group (1) was given an equal volume of saline intraperitoneally. REF001024 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL00030 H9c2 Ferroptosis (hsa04216) Cell ferroptosis
unique00680 Resveratrol (Res) attenuated 5-FU-induced bodyweight reduction, restored the cardiac dysfunction and reduced the activity of oxidative stress. Furthermore, inhibition of GPX4-mediated ferroptosis was the protective mechanisms of Res against 5-FU-induced cardiotoxicity. Suppressor . Up regulation . . Suppressor Adult male C57BL/6J mice weighing 20 ± 2 g were purchased from Chongqing Tengxin Biotechnology. Mice were housed at 22 with a 12 h light/dark cycle with free access to food and water. The cardiotoxicity mice model was induced by intraperitoneal injection of 5-FU (30 mg/kg) for 7 days. The cardiotoxicity mice were randomly divided into five groups: model group (normal saline), Res low, medium, high dose group (1, 2, 4 mg/kg) and Fer-1 positive control group (2.5 mg/kg). These mice were given Res or Fer-1 once a day for 3 weeks, with the body weight being recorded. Then, the mice were euthanized, blood samples and heart tissue were collected. REF000903 ICD-11: BC43 5-FU-induced cardiotoxicity CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01272 lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and Diabetic cardiomyopathy development. Inhibition of ZFAS1 restored the expression of FTH1, reduced the expression of 4HNE, rescued the expression of GPX4 and inhibited the expression of apoptosisrelated genes. . . . Up regulation Suppressor Suppressor To simulate the animal model of diabetic cardiomyopathy, male db/+ mice and db/db mice (age, 7 weeks, weight, 24 g) were fed a normal diet for 4 weeks and kept at 24 under a 14-h light/8-h dark cycle. The animals were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). Diabetic mice were intracoronarily administered equal volumes (80 ul) of adenoviruses Ad-ZFAS1, Ad-sh-ZFAS1, Ad-CCND2, Ad-sh-CCND2 or Ad-NC.33 miR-150-5p mimics and mimic control (NC) were injected into the tail vein of mice (50 ug/kg) every 15 days for 12 weeks. Db/db mice were treated with or without ferrostatin-1 (Fer-1, ferroptosis inhibitor; Sigma-Aldrich, 5 mg/kg) for an additional 12 weeks. REF000526 ICD-11: BC43.7 Diabetic cardiomyopathy CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01273 lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and Diabetic cardiomyopathy development. Inhibition of ZFAS1 restored the expression of FTH1, reduced the expression of 4HNE, rescued the expression of GPX4 and inhibited the expression of apoptosisrelated genes. . . . Up regulation Suppressor Suppressor To simulate the animal model of diabetic cardiomyopathy, male db/+ mice and db/db mice (age, 7 weeks, weight, 24 g) were fed a normal diet for 4 weeks and kept at 24 under a 14-h light/8-h dark cycle. The animals were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). Diabetic mice were intracoronarily administered equal volumes (80 ul) of adenoviruses Ad-ZFAS1, Ad-sh-ZFAS1, Ad-CCND2, Ad-sh-CCND2 or Ad-NC.33 miR-150-5p mimics and mimic control (NC) were injected into the tail vein of mice (50 ug/kg) every 15 days for 12 weeks. Db/db mice were treated with or without ferrostatin-1 (Fer-1, ferroptosis inhibitor; Sigma-Aldrich, 5 mg/kg) for an additional 12 weeks. REF000526 ICD-11: BC43.7 Diabetic cardiomyopathy CELL10051 cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis
unique01236 MITOL/ MARCH5 is an E3 ubiquitin ligase that plays a crucial role in the control of mitochondrial quality and function. The mitochondrial ubiquitin ligase MITOL is identified as a novel regulator of DOX-induced cardiomyopathy. A knockdown of MITOL in cardiomyocytes reduced GPX4 to induce the accumulation of lipid peroxide, resulting in ferroptosis. . . . Up regulation Suppressor Suppressor In all experiments using KO mice (male, 8-12 weeks), we used age-matched, tamoxifen-treated MerCreMer single-genotype animals as controls. For inducing cardiac-specific knockout of MITOL, an ethanol-corn oil emulsion of tamoxifen (TAX; H5648, Sigma-Aldrich) was injected intraperitoneally per day of 30 mg tamoxifen/kg body weight (150 mg/kg total) for 5 days. REF000480 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL10051 Cardiomyocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00557 The inhibitory action of ethoxyquin against GPx4-deficient ferroptosis and its therapeutic efficacy against DOX-induced cell death in cultured cardiomyocytes and cardiotoxicity in a murine model of doxorubicin-induced cardiomyopathy (DIC). Suppressor . Up regulation . . Suppressor DOX (D1515, Sigma-Aldrich, St Louis, MO, USA; 6 mg/kg, dissolved in distilled water) was administrated to C57BL/6J Male mice (8-10 weeks old, 21-24 g) via the tail vein on days 0, 2, and 4.Ethoxyquin(E0237, Tokyo Chemical Industry, Tokyo, Japan; 100 umol/kg, once a day) was orally administrated every day from days 0 to 14. Ethoxyquinwas dissolved in polyethylene glycol (PEG; 28214-05, Nacalai Tesque, Kyoto, Japan,ethoxyquin10 uL in 990 uL PEG), and the solution was then diluted in the same amount of normal saline (873311, Otsuka Pharmaceutical, Tokyo, Japan). REF000790 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL10051 cardiomyocytes Ferroptosis (hsa04216) Cell ferroptosis
unique00562 Curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy. Suppressor . Up regulation . . Suppressor Two-month-old male New Zealand rabbits purchased from the Medical Experimental Animal Center of Bengbu Medical College were used as experimental subjects. Streptozotocin was dissolved in sterile saline and intraperitoneally injected into the rabbits at a dose of 80 mg/kg. The rabbits were allowed to eat freely after receiving the injection. The fasting blood glucose levels of the rabbits were monitored regularly. The diabetic rabbit model was considered successfully established when the fasting blood glucose level was measured as 11 mmol/L twice or 14 mmol/L once. Following successful modelling, grouping was performed as follows: blank control group (Con-Group), diabetic rabbit group (DM-Group), diabetic rabbit + every other day curcumin administration group (Qod-Group), and diabetic rabbit + daily administration group (Qd-Group). REF000792 ICD-11: BC43.7 Diabetic cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01206 ENPP2 was transcriptionally regulated by FoxO4 to protect cardiomyocytes from Doxorubicininduced cardiotoxicity by inhibiting ferroptosis. In addition, the inhibitory effects of ENPP2 on Dox-induced ferroptosis were significantly reduced by FoxO4 overexpression, as demonstrated by increased Fe2+ and lipid ROS activity levels, decreased SLC7A11, GPX4 and FPN1 expression, and increased NOX4 expression, which were observed following FoxO4 overexpression. . . . Up regulation Driver Driver . REF000460 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01710 Berberine (Ber) downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against imatinib mesylate-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis. Suppressor . Up regulation . . Suppressor All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. REF000931 ICD-11: BC43.20 Cardiotoxicity induced by IMA CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01707 Berberine (Ber) downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against imatinib mesylate-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis. Suppressor . Up regulation . . Marker/Suppressor All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. REF000931 ICD-11: BC43.20 Cardiotoxicity induced by IMA CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00561 Curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy. Suppressor . Up regulation . . Marker/Suppressor Two-month-old male New Zealand rabbits purchased from the Medical Experimental Animal Center of Bengbu Medical College were used as experimental subjects. Streptozotocin was dissolved in sterile saline and intraperitoneally injected into the rabbits at a dose of 80 mg/kg. The rabbits were allowed to eat freely after receiving the injection. The fasting blood glucose levels of the rabbits were monitored regularly. The diabetic rabbit model was considered successfully established when the fasting blood glucose level was measured as 11 mmol/L twice or 14 mmol/L once. Following successful modelling, grouping was performed as follows: blank control group (Con-Group), diabetic rabbit group (DM-Group), diabetic rabbit + every other day curcumin administration group (Qod-Group), and diabetic rabbit + daily administration group (Qd-Group). REF000792 ICD-11: BC43.7 Diabetic cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00256 Adriamycin (ADR) was found to promote cardiac ferroptosis, whereas administration of Astragaloside IV (AsIV) attenuated the process via activating Nrf2 signaling pathway and the subsequent GPX4 expression increasing. These results suggest that AsIV might play a protective role against ADR-induced myocardial fibrosis. Suppressor . Up regulation . . Marker/Suppressor A total of 24 SD male rats weighing 200-210 g from the Vital River Laboratory Animal Technology Co., Ltd. were divided randomly into control, ADR, ADR+AsIV, and AsIV group (n = 6). AsIV was administered by gavage at a dose of 10 mg/kg/day over a period of five weeks. ADR was administered intraperitoneally once a week (30 mg/kg/week) for five weeks. Controls were administered saline intraperitoneally (i.p.) at the same dose as ADR and intragastrically at the same dose as AsIV. REF000344 ICD-11: BC43 Adriamycin induced cardiomyopathy CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01589 Berberine (BBR) inhibited ferroptosis via reducing ROS generation and reducing lipid peroxidation in erastin and RSL3-treated cardiac cells.Furthermore, quantitative polymerase chain reaction results showed that Ptgs2 mRNA was reduced in BBR-treated cells. BBR has the potential to treat ferroptosis-induced cardiomyopathy. Suppressor . Down regulation . . Marker . REF000795 ICD-11: BC43 Cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00660 Atorvastatin (ATV) intervention blocked erastin or H/R-induced ferroptosis in H9C2 cells by activating SMAD7 expression and thereby down-regulating the hepcidin/FPN1 pathway. The in vivo study also demonstrated that ATV inhibited ferroptosis in ischemia-reperfusion rat myocardium through the SMAD7/hepcidin pathway. Suppressor Up regulation . . . Suppressor A total of 18 Wistar rats (250~300 g) were purchased from Hunan slake Jingda experimental animal Co., Ltd. The rats were randomly divided into the Sham group, I/R group, and I/R + ATV group (n = 6/group).They received standard diet and water before myocardial I/R. Rats in the I/R + ATV group were orally treated with ATV (10 mg/kg/d) for 2 weeks before myocardial I/R (9).The Sham and I/R model rats were constructed as follows: The rats were anesthetized with sodium pentobarbital (50 mg/kg, intraperitoneal injection), ligation of the left anterior descending branch with 4-0 silk thread for 30 min, and then reperfusion for 180 min. In the sham control group, the entire procedure was performed with silk thread passing below the coronary artery, but the LAD coronary artery was not ligated. At the end of reperfusion, the rats were given excessive isoflurane for 10 min and sacrificed by bloodletting. Then the rat myocardial tissues were isolated for subsequent detection. REF000888 ICD-11: BC43 Ischemia-reperfusion cardiomyopathy CELL00030 H9C2 Ferroptosis (hsa04216) Cell ferroptosis
unique00644 Canagliflozin (Cana) promotes upregulation of SLC7A11 and downregulation of TfR1 and FTN-H, which protect the cardiomyocytes from ferroptosis. These finding suggests that Cana inhibit ferroptosis by balancing cardiac iron homeostasis and promoting the system Xc/GSH/GPX4 axis in diabetic cardiomyopathy. Suppressor . Up regulation . . Suppressor Male C57BL/6J mice aged 6-8 weeks with weights of 18-20 g were obtained from the Slack Laboratory Animal Co., Ltd. (Shanghai, China). Mice were allowed to acclimatize in the laboratory environment for 1 week before the beginning of the experiment. DCM model establishment: The mice were given a single intraperitoneal injection of 150 mg/kg 1% streptozotocin (STZ, V900890, Sigma, USA, dissolved in 0.1 mol/L sodium citrate buffer, pH = 4.4 - 4.6). Mouse blood from the tail vein was collected in each group of the model mice and tested by glucose meter (Accu-Chek Performa test strips, Roche, Accu-Chek Performa Combo, Roche, USA) on day 3, 5 and 7 after injection. REF000875 ICD-11: BC43.7 Diabetic cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00807 Liquiritin can protect the doxorubicin-induce mice's cardiotoxicity, and its beneficial effect is related to the reduction of ferroptosis through a mechanism involving the regulation of the SLC7A11/GPX4 pathway. Suppressor . Up regulation . . Suppressor The set of animal experiments was designed to evaluate the effectiveness of liquiritin on doxorubicin-induced cardiotoxicity as were as ferroptosis were explored. Mice were randomly divided into 5 groups: (1) the control group; (2) doxorubicin group; (3) the doxorubicin plus liquiritin group (20 mg/kg); (4) the doxorubicin plus liquiritin group (40 mg/kg); (5) the doxorubicin plus liquiritin group (80 mg/kg) (Han et al.2022; Mou et al.2021). The control group and doxorubicin group were given equal volume of 0.5% sodium carboxymethylcellulose; the doxorubicin plus liquiritin groups were given different doses of liquiritin (0.5%) sodium carboxymethylcellulose co-suspension) by intragastric administration 7 days in advance once a daily. On day 8, groups (2), (3), (4), and (5) were given a single intraperitoneal injection of 15 mg/kg of DOX to establish a model of doxorubicin-induced cardiotoxicity; and group (1) was given an equal volume of saline intraperitoneally. REF001024 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL00030 H9c2 Ferroptosis (hsa04216) Cell ferroptosis
unique00645 Canagliflozin (Cana) promotes upregulation of SLC7A11 and downregulation of TfR1 and FTN-H, which protect the cardiomyocytes from ferroptosis. These finding suggests that Cana inhibit ferroptosis by balancing cardiac iron homeostasis and promoting the system Xc/GSH/GPX4 axis in diabetic cardiomyopathy. Suppressor . Down regulation . . Driver Male C57BL/6J mice aged 6-8 weeks with weights of 18-20 g were obtained from the Slack Laboratory Animal Co., Ltd. (Shanghai, China). Mice were allowed to acclimatize in the laboratory environment for 1 week before the beginning of the experiment. DCM model establishment: The mice were given a single intraperitoneal injection of 150 mg/kg 1% streptozotocin (STZ, V900890, Sigma, USA, dissolved in 0.1 mol/L sodium citrate buffer, pH = 4.4 - 4.6). Mouse blood from the tail vein was collected in each group of the model mice and tested by glucose meter (Accu-Chek Performa test strips, Roche, Accu-Chek Performa Combo, Roche, USA) on day 3, 5 and 7 after injection. REF000875 ICD-11: BC43.7 Diabetic cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01291 The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. MiR-7-5p could effectively suppress METLL14 and TFRC expression. The study suggested a therapeutic strategy to alleviate doxorubicin (DOX)-induced cardiomyopathy. . . . Up regulation Driver Marker/Suppressor/Driver Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks. REF000540 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00286 AC16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01290 The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. MiR-7-5p could effectively suppress METLL14 and TFRC expression. The study suggested a therapeutic strategy to alleviate doxorubicin (DOX)-induced cardiomyopathy. . . . Down regulation Suppressor Marker/Suppressor/Driver Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks. REF000540 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00286 AC16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00659 Atorvastatin intervention blocked erastin or H/R-induced ferroptosis in H9C2 cells by activating SMAD7 expression and thereby down-regulating the hepcidin/FPN1 pathway. The in vivo study also demonstrated that ATV inhibited ferroptosis in ischemia-reperfusion cardiomyopathy rat myocardium through the SMAD7/hepcidin pathway. Suppressor Up regulation . . Suppressor . A total of 18 Wistar rats (250~300 g) were purchased from Hunan slake Jingda experimental animal Co., Ltd. The rats were randomly divided into the Sham group, I/R group, and I/R + ATV group (n = 6/group).They received standard diet and water before myocardial I/R. Rats in the I/R + ATV group were orally treated with ATV (10 mg/kg/d) for 2 weeks before myocardial I/R (9).The Sham and I/R model rats were constructed as follows: The rats were anesthetized with sodium pentobarbital (50 mg/kg, intraperitoneal injection), ligation of the left anterior descending branch with 4-0 silk thread for 30 min, and then reperfusion for 180 min. In the sham control group, the entire procedure was performed with silk thread passing below the coronary artery, but the LAD coronary artery was not ligated. At the end of reperfusion, the rats were given excessive isoflurane for 10 min and sacrificed by bloodletting. Then the rat myocardial tissues were isolated for subsequent detection. REF000888 ICD-11: BC43 Ischemia-reperfusion cardiomyopathy CELL00030 H9C2 Ferroptosis (hsa04216) Cell ferroptosis
unique00346 Dexrazoxane (DXZ) reduces cytotoxicity caused by Doxorubicin (DOX). HMGB1 was induced by DOX but was inhibited by DXZ or FER-1. Overexpression of HMGB1 promoted the ferroptosis and cardiotoxicity induced by DOX in the rats although silencing of HMGB1 showed opposite effects. Suppressor Down regulation . . Driver . Male Wistar rats (250-300 g,n = 230) were purchased from Vitalriver. Ten rats were recruited in each group in the experiment. The rats in the control, DOX, FER-1 + DOX, NEC-1 + DOX, 3-MA + DOX, and Emricasan + DOX groups were used for the overall survival analysis, and those from control and DOX groups were used for detection of the expression of PTGS2 in the indicated organs of rats. REF000471 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00430 Epigallocatechin-3-gallate pretreatment upregulated the expression and phosphorylation of AMPK2 and activated adaptive autophagy, thus decreasing iron accumulation, inhibiting excess ROS generation and abnormal lipid metabolism, increasing energy supply, and maintaining mitochondrial function, ultimately protecting the myocardium against Dox-induced cardiotoxicity (DIC)-induced ferroptosis. Suppressor Up regulation . . Suppressor . Mice were reseparated into 5 groups: control, Dox, Dox + Fer-1, Dox + EGCG, and Dox + EGCG+compound C groups. The Dox group mice were administered 6 intraperitoneal (ip) injections of 2.5 mg/kg Dox over 3 weeks for a cumulative dose of 15 mg/kg. Mice in the Dox + Fer-1 group were ip injected with 1 mg/kg/d Fer-1 for 2 weeks as in the Dox group. Mice in the Dox + EGCG group were intragastrically (ig) injected 20 mg/kg/d EGCG (dissolved in normal saline) for six consecutive weeks; Dox was administered 1 h prior to this as in the Dox group. Mice in the Dox + EGCG + compound C group were treated using the same method as in the Dox + EGCG group for four consecutive weeks, followed by ip injections of 10 mg/kg/d compound C for 2 weeks. Mice in the control groups were administered an equal volume of normal saline via gavage for 6 weeks. REF000579 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00030 H9C2 Ferroptosis (hsa04216); Autophagy (hsa04140); mTOR signaling pathway (hsa04150) Cell ferroptosis; Cell autophagy
unique00497 Salidroside markedly down-regulated ferroptotic cell death by activating AMPK-dependent signaling pathways including regulating abnormal fatty acid metabolism and maintaining mitochondrial function. Therefore, salidroside is can be exploited to develop a novel medication for clinical Doxorubicin-induced cardiotoxicity. Suppressor Up regulation . . Suppressor . Male C57/BL mice (aged between 6 and 8 weeks and weighing 20 ± 2 g) were randomly divided into 6 groups (n = 6 mice per group) with equal number of mice in each group. The groups included saline control group (control group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days; DOX model group (DOX group): 200 ulxd-1 saline intraperitoneally administered to the mice for 10 days and a single intraperitoneal administration of 10 mgxkg-1 DOX (HY-15,142, MCE, China) to the mice on the seventh day. REF000666 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01022 Both in vitro and in vivo experiments proved the downregulation of Acot1 in doxorubicin-induced cardiotoxicity (DIC), which can be partially prevented with Fer-1 treatment. Acot1 may become a potential treating target in preventing doxorubicin-induced cardiotoxicity by anti-ferroptosis. Inducer Down regulation . . Suppressor . C57BL/6 male mice (20-25 g) at 7 weeks were purchased from the Vital River Laboratory Animal Technology Co., Ltd. Two doses of DOX was administrated by intraperitoneal injection, 15 mg/kg at Day 1, and 10 mg/kg at Day 8. Mice were then killed at Day 15 after transthoracic echocardiography examination. REF000231 ICD-11: BC43.20 Doxorubicin-induced cardiotoxicity CELL00548 HL-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01289 The RNA-binding protein IGF2BP1 is associated with KCNQ1OT1 to increase its stability and robustly inhibit miR-7-5p activity. MiR-7-5p could effectively suppress METLL14 and TFRC expression. The study suggested a therapeutic strategy to alleviate doxorubicin (DOX)-induced cardiomyopathy. Inducer Up regulation . . Driver . Male Sprague-Dawley rats (6-8 weeks old; weighed from 210 to 230 g) were purchased from HFK Bioscience Co. Ltd. Rats were randomly assigned to four groups (n = 6 per group). The first was the control group, which were treated daily with 0.5 ml of 0.9% saline by intraperitoneal injection for 14 days, and there were three DOX model groups, which were treated three times weekly with 2.5 mg/kg of DOX by intraperitoneal injection for 14 weeks. At day 14, mice in the DOX model groups were infected through an intramyocardial injection of either control shNC or shMettl14 (1 x 109 titer) at three distinct locations in the left ventricular free wall three times a week for 2 weeks, and they were treated daily with 30 mg/kg of ferroptosis inducer erastin (MedChemExpress, USA) through intragastric administration or vehicle control (Saline) for 2 weeks. REF000540 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00286 AC16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00649 LCZ696 treatment increased SIRT3 expression and deacetylated its target gene SOD2, and these changes were mediated by AKT activation. Collectively,LCZ696 prevents DOX-induced cardiotoxicity by inhibiting ferroptosis via AKT/SIRT3/SOD2 signaling pathway activation. Suppressor Up regulation . . Suppressor . All animal protocols were approved by the Animal Care and Use Committee of TaizhouHospital, affiliated to Zhejiang University (Taizhou, China). Twenty-four 2-month-old male Wistar rats weighing 190-220 g were purchased from the Experimental Animal Center of Basi Medicine, Zhejiang Chinese Medical University. The animals were reared under a 12 h light/12 h dark cycle at a relative humidity of 55 ± 5% and temperature of 23 ± 2 , with unrestricted access to food and water. All animals were acclimatized to laboratory conditions for 1 week before the experiments and were randomly divided into four groups: control group (CG, n = 6); LCZ696 group (LCZ, n = 6); DOX group (DOX, n = 6); and DOX + LCZ696 group (DOX + LCZ, n = 6). The CG received saline solution by gavage for 6 weeks (2 mL/day), while the treatment groups received DOX (Cat. HY-15142A, MedChemExpress, USA), LCZ696 (Cat. HY-18204A, MedChemExpress, USA), or DOX + LCZ696. DOX was administered at a dose of 2.5 mg/kg once a week for 6 weeks via tailvein injection. LCZ696 (60 mg/kg/day) was administered by gavage for 6 weeks. Body weight was measured weekly. REF000878 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00030 H9C2 Ferroptosis (hsa04216) Cell ferroptosis
unique00751 Astragaloside IV decreased cardiomyocyte injury and myocardial dysfunction by inhibiting ferroptosis mediated by CD36 in diabetic cardiomyopathy rats. Therefore, AS-IV regulated the lipid metabolism of cardiomyocytes and inhibited cellular ferroptosis, which may have potential clinical value in DCM treatment. Suppressor Down regulation . . Driver . Male Sprague-Dawley (SD) rats (160-180 g) were purchased from the Experimental Animal Center of Guangzhou University of Chinese Medicine. After 1 week of acclimatization, the rats were randomly divided into two groups: the control group (standard diet,n = 6) and the high-fat diet (HFD) group. The control group was given a standard diet for 8 weeks, and the HFD group was given a high-fat diet (feed item No. D12451, Guangdong Medical Laboratory Animal Center) for 8 weeks. Subsequently, intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) was performed in the HFD group for inducing diabetic symptoms, and an equal volume of saline was given to the control group. A diabetes model was successfully established under the condition that the fasting blood glucose levels were > 16.7 mmol/L over three consecutive days. Diabetic rats in the HFD group were divided into five groups: a DCM group, three AS-IV treatment groups (20, 40, and 80 mg/kg/day by gavage,n = 6), and an atorvastatin treatment group (ALE group, used as a positive control drug, 10 mg/kg, by gavage,n = 6). Rats were given the standard diet during drug gavage. After 12 weeks of treatment, all animals were anesthetized and then euthanized by intraperitoneal injection with an overdose of pentobarbital sodium. The animal experiments in this study were randomized and single-blind. REF000976 ICD-11: BC43.7 Diabetic cardiomyopathy CELL00030 H9C2 Ferroptosis (hsa04216) Cell ferroptosis
unique00650 LCZ696 treatment increased SIRT3 expression and deacetylated its target gene SOD2, and these changes were mediated by AKT activation. Collectively, LCZ696 prevents DOX-induced cardiotoxicity by inhibiting ferroptosis via AKT/SIRT3/SOD2 signaling pathway activation. Suppressor Up regulation . . Suppressor . All animal protocols were approved by the Animal Care and Use Committee of TaizhouHospital, affiliated to Zhejiang University (Taizhou, China). Twenty-four 2-month-old male Wistar rats weighing 190-220 g were purchased from the Experimental Animal Center of Basi Medicine, Zhejiang Chinese Medical University. The animals were reared under a 12 h light/12 h dark cycle at a relative humidity of 55 ± 5% and temperature of 23 ± 2 , with unrestricted access to food and water. All animals were acclimatized to laboratory conditions for 1 week before the experiments and were randomly divided into four groups: control group (CG, n = 6); LCZ696 group (LCZ, n = 6); DOX group (DOX, n = 6); and DOX + LCZ696 group (DOX + LCZ, n = 6). The CG received saline solution by gavage for 6 weeks (2 mL/day), while the treatment groups received DOX (Cat. HY-15142A, MedChemExpress, USA), LCZ696 (Cat. HY-18204A, MedChemExpress, USA), or DOX + LCZ696. DOX was administered at a dose of 2.5 mg/kg once a week for 6 weeks via tailvein injection. LCZ696 (60 mg/kg/day) was administered by gavage for 6 weeks. Body weight was measured weekly. REF000878 ICD-11: BC43 Doxorubicin induced cardiomyopathy CELL00030 H9C2 Ferroptosis (hsa04216) Cell ferroptosis
unique01711 Berberine downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis. Suppressor Down regulation . . Driver . All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. REF000931 ICD-11: BC43.20 Cardiotoxicity induced by IMA CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01361 LncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs. . . . Up regulation Driver Marker/Suppressor/Driver The rats were randomly divided into five groups as follows: (1) sham group: the rats underwent sham operation and received vehicle (PBS, caudal vein injection). (2) Model group: the rats were subjected to AAC and received vehicle (PBS, caudal vein injection). (3-5) The treatment groups: the rats were subjected to AAC and after 24 h treated with si-AAB, si-AAB + MSN, or NM + si-AAB + MSN (50 nM siRNA dose per rat every 2 days for 4 weeks, caudal vein injection). REF000620 ICD-11: BC45 Cardiac hypertrophy CELL10041; CELL10167 Neutrophils; CMECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01362 LncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs. . . . Down regulation Suppressor Marker/Suppressor/Driver The rats were randomly divided into five groups as follows: (1) sham group: the rats underwent sham operation and received vehicle (PBS, caudal vein injection). (2) Model group: the rats were subjected to AAC and received vehicle (PBS, caudal vein injection). (3-5) The treatment groups: the rats were subjected to AAC and after 24 h treated with si-AAB, si-AAB + MSN, or NM + si-AAB + MSN (50 nM siRNA dose per rat every 2 days for 4 weeks, caudal vein injection). REF000620 ICD-11: BC45 Cardiac hypertrophy CELL10041; CELL10167 Neutrophils; CMECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01360 LncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs. . . . Down regulation Suppressor Driver The rats were randomly divided into five groups as follows: (1) sham group: the rats underwent sham operation and received vehicle (PBS, caudal vein injection). (2) Model group: the rats were subjected to AAC and received vehicle (PBS, caudal vein injection). (3-5) The treatment groups: the rats were subjected to AAC and after 24 h treated with si-AAB, si-AAB + MSN, or NM + si-AAB + MSN (50 nM siRNA dose per rat every 2 days for 4 weeks, caudal vein injection). REF000620 ICD-11: BC45 Cardiac hypertrophy CELL10041 Neutrophils Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01359 LncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/ TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs. . . . Up regulation Driver Driver The rats were randomly divided into five groups as follows: (1) sham group: the rats underwent sham operation and received vehicle (PBS, caudal vein injection). (2) Model group: the rats were subjected to AAC and received vehicle (PBS, caudal vein injection). (3-5) The treatment groups: the rats were subjected to AAC and after 24 h treated with si-AAB, si-AAB + MSN, or NM + si-AAB + MSN (50 nM siRNA dose per rat every 2 days for 4 weeks, caudal vein injection). REF000620 ICD-11: BC45 Cardiac hypertrophy CELL10041 Neutrophils Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01166 MiR-224-5p was indeed the downstream target of circSnx12, and miR-224-5p could bind to the 3'-UTR region of FTH1 and regulate its expression level. Therefore, it is speculated that low circSnx12 expression and high miR-224-5p expression can downregulate FTH1 expression, directly regulate iron overload in myocardial cells, and ultimately leads to cardiac cell death. This new approach reveals potential circRNA targets for the treatment of heart failure. . . . Down regulation Driver Marker/Suppressor Six-week-old male C57/BL6J mice (weighting ~18-20 g) were supplied by the Shenyang Military Region General Hospital Experimental Animal Center. The mice were fed a standard diet and had unlimited access to drinking water. After 2 weeks of feeding, the mice were randomly assigned to TAC group (n = 15) and SHAM group (n = 16), and then anesthetized by intraperitoneal injection of 50 mg/kg pentobarbital sodium. To allow direct access to the transverse aorta, the mice a horizontal incision (5 mm in length) was made at the suprasternal notch. TAC operation was then performed by ligating the aorta between the right innominate and left carotid arteries using a 27G needle tied with 7-0 silk suture. The needle was promptly withdrawn, leaving the aortic constriction in place. The surgical procedure of mice in SHAM group was similar to that of mice in TAC group, except that the 7-0 silk suture was only crossed through the aortic arch without ligation. REF000403 ICD-11: BD10 Heart failure CELL10136 Myocardial tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01165 MiR-224-5p was indeed the downstream target of circSnx12, and miR-224-5p could bind to the 3'-UTR region of FTH1 and regulate its expression level. Therefore, it is speculated that low circSnx12 expression and high miR-224-5p expression can downregulate FTH1 expression, directly regulate iron overload in myocardial cells, and ultimately leads to cardiac cell death. This new approach reveals potential circRNA targets for the treatment of heart failure. . . . Up regulation Suppressor Marker/Suppressor Six-week-old male C57/BL6J mice (weighting ~18-20 g) were supplied by the Shenyang Military Region General Hospital Experimental Animal Center. The mice were fed a standard diet and had unlimited access to drinking water. After 2 weeks of feeding, the mice were randomly assigned to TAC group (n = 15) and SHAM group (n = 16), and then anesthetized by intraperitoneal injection of 50 mg/kg pentobarbital sodium. To allow direct access to the transverse aorta, the mice a horizontal incision (5 mm in length) was made at the suprasternal notch. TAC operation was then performed by ligating the aorta between the right innominate and left carotid arteries using a 27G needle tied with 7-0 silk suture. The needle was promptly withdrawn, leaving the aortic constriction in place. The surgical procedure of mice in SHAM group was similar to that of mice in TAC group, except that the 7-0 silk suture was only crossed through the aortic arch without ligation. REF000403 ICD-11: BD10 Heart failure CELL10136 Myocardial tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00907 TLR4 or NOX4 knock-down significantly improved left ventricular remodeling and reduced myocytes death. Simultaneously, activated autophagy and ferroptosis in rats with heart failure (HF) were remarkably retarded by either TLR4 and NOX4 knock-down, suggesting TLR4-NOX4 as a potential therapeutic target for HF through inhibiting autophagy- and ferroptosis-mediated cell death. . . . Up regulation Driver Driver Present animal studies used male Sprague Dawley rats (80-100 g) to create a HF model induced by the descending aortic banding (AB) procedure. The sham-operated (SO) group was defined as rats subjected to a similar procedure with the exception of arterial ligation. Echocardiography was applied to confirm the arterial banding immediately after the surgical procedure. REF000073 ICD-11: BD10 Heart failure CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01244 Atorvastatin showed significantly protective effects through suppressing the activation of ferroptosis related signaling, as evidenced by decreasing the mRNA levels of PTGS2 (a marker of ferroptosis), contents of malonaldehyde and protein levels of NOX4 and increasing the contents of glutathione (GSH), the ratio of GSH/GSSG and protein levels of GPX4 and SLC7A11. ATV reduced cardiac hypertrophy and fibrosis and accumulation of iron in heart failure. Suppressor . Down regulation . . Driver 8-week C57BL/6J male mice purchased from Comparative Medicine Center of Yangzhou University were retained with unrestricted access to sterilized diet and water at standard bio-clean laboratory settings (Experimental Animal Center of College of Veterinary Medicine of Yangzhou University). Animals were randomly divided into four groups(n = 6-8 mice per group): control group or ISO group: injected with saline or ISO (5 mg/kg) subcutaneously for 14 days and, meanwhile, received vehicle saline via gavage for 14 days respectively; ATV (Pfizer,USA) group or ISO + ATV group: injected with saline or 5 mg/kg ISO (Sigma, USA) subcutaneously for 14 days and, meanwhile, received 20 mg/kg ATV via gavage for 14 days respectively. REF000490 ICD-11: BD10 Heart failure CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique00013 Ferroptosis is involved in the loss of myocytes during heart failure. Puerarin exerted protective effects against heart failure through inhibition of ferroptosis. And puerarin exerted protective effects against heart failure through inhibition of ferroptosis. Regulation of Nox4 signaling might be involved in puerarin inhibiting ferroptosis. Suppressor . Down regulation . . Driver Male Sprague Dawley ratsweighing 80-100 g were used to make the HF model induced by descending aortic banding (AB) procedure. Rats receiving a similar procedure except for the arterial ligation were defined as the sham-operated (SO) group. After the procedure, echocardiography was immediately applied to confirm the arterial banding. Rats receiving subcutaneous injections of low- or high-dose puerarin (100 mg/kg/day and 200 mg/kg/day, respectively) after the AB procedure were respectively defined as the Pue1 and Pue2 groups. An equal volume of normal saline was injected into the rats of the SO and AB groups. REF000036 ICD-11: BD10 Heart failure CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01243 Atorvastatin showed significantly protective effects through suppressing the activation of ferroptosis related signaling, as evidenced by decreasing the mRNA levels of PTGS2 (a marker of ferroptosis), contents of malonaldehyde and protein levels of NOX4 and increasing the contents of glutathione (GSH), the ratio of GSH/GSSG and protein levels of GPX4 and SLC7A11. ATV reduced cardiac hypertrophy and fibrosis and accumulation of iron in heart failure. Suppressor . Down regulation . . Marker 8-week C57BL/6J male mice purchased from Comparative Medicine Center of Yangzhou University were retained with unrestricted access to sterilized diet and water at standard bio-clean laboratory settings (Experimental Animal Center of College of Veterinary Medicine of Yangzhou University). Animals were randomly divided into four groups(n = 6-8 mice per group): control group or ISO group: injected with saline or ISO (5 mg/kg) subcutaneously for 14 days and, meanwhile, received vehicle saline via gavage for 14 days respectively; ATV (Pfizer,USA) group or ISO + ATV group: injected with saline or 5 mg/kg ISO (Sigma, USA) subcutaneously for 14 days and, meanwhile, received 20 mg/kg ATV via gavage for 14 days respectively. REF000490 ICD-11: BD10 Heart failure CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique01242 Atorvastatin showed significantly protective effects through suppressing the activation of ferroptosis related signaling, as evidenced by decreasing the mRNA levels of PTGS2 (a marker of ferroptosis), contents of malonaldehyde and protein levels of NOX4 and increasing the contents of glutathione (GSH), the ratio of GSH/GSSG and protein levels of GPX4 and SLC7A11. ATV reduced cardiac hypertrophy and fibrosis and accumulation of iron in heart failure. Suppressor . Up regulation . . Suppressor 8-week C57BL/6J male mice purchased from Comparative Medicine Center of Yangzhou University were retained with unrestricted access to sterilized diet and water at standard bio-clean laboratory settings (Experimental Animal Center of College of Veterinary Medicine of Yangzhou University). Animals were randomly divided into four groups(n = 6-8 mice per group): control group or ISO group: injected with saline or ISO (5 mg/kg) subcutaneously for 14 days and, meanwhile, received vehicle saline via gavage for 14 days respectively; ATV (Pfizer,USA) group or ISO + ATV group: injected with saline or 5 mg/kg ISO (Sigma, USA) subcutaneously for 14 days and, meanwhile, received 20 mg/kg ATV via gavage for 14 days respectively. REF000490 ICD-11: BD10 Heart failure CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique00748 Levosimendan reversed mitochondrial malfunction in heart failure with preserved ejection fraction (HFpEF) mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. Levosimendan reverses cardiac malfunction and cardiomyocyte ferroptosis during heart failure with preserved ejection fraction via connexin 43 signaling activation. Suppressor . Up regulation . . Suppressor We purchased forty-eight 3-week-old male C57BL/6N mice from Beijing HFK Bioscience Co. Ltd. and gave a twelve-hour light and dark cycle starting from 06:00 (am) to 18:00 (pm). Mice were randomly assigned into three groups after 2 weeks of adaptive feeding as follows. (1) The control group (n = 16): mice were provided with normal drinking water, a normal diet and intraperitoneal administration of solvent (5% DMSO + 40% Peg300 + 5% Tween 80 + 50% ddH2O) 3 mL/kg once a week aged 13 to 17 weeks. (2) The HFpEF group (n = 16): a double-hit model was designed, in which metabolic and mechanical stress worked together and resulted in HFpEF. Briefly, C57BL/6N mice had unrestricted access to a high-fat diet (HFD, D12492, Research Diet) starting from 5 weeks old. Meanwhile, a nitric oxide synthase inhibitor, N (gamma)-nitro-L-arginine methyl ester (L-NAME) (N5751, Sigma) was supplied in drinking water (0.5 g/L) for HFpEF groups, and the pH of the drinking water was adjusted to 7.4. The above placebo solvent was administrated in the same manner. (3) The HFpEF + Levo group (n = 16): according to the previous study, HFpEF mice received 3 mg/kg levosimendan (S2446, Selleck) (Dissolve 1 mg of levosimendan in 50 uL of DMSO, subsequently dilute to 1 mg/mL with the above solvent) intraperitoneally once a week from week 13 to 17. REF000975 ICD-11: BD11 Left ventricular failure CELL10171 Heart tissues Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00750 Levosimendan reversed mitochondrial malfunction in heart failure with preserved ejection fraction (HFpEF) mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. Levosimendan reverses cardiac malfunction and cardiomyocyte ferroptosis during heart failure with preserved ejection fraction via connexin 43 signaling activation. Suppressor . Down regulation . . Driver We purchased forty-eight 3-week-old male C57BL/6N mice from Beijing HFK Bioscience Co. Ltd. and gave a twelve-hour light and dark cycle starting from 06:00 (am) to 18:00 (pm). Mice were randomly assigned into three groups after 2 weeks of adaptive feeding as follows. (1) The control group (n = 16): mice were provided with normal drinking water, a normal diet and intraperitoneal administration of solvent (5% DMSO + 40% Peg300 + 5% Tween 80 + 50% ddH2O) 3 mL/kg once a week aged 13 to 17 weeks. (2) The HFpEF group (n = 16): a double-hit model was designed, in which metabolic and mechanical stress worked together and resulted in HFpEF. Briefly, C57BL/6N mice had unrestricted access to a high-fat diet (HFD, D12492, Research Diet) starting from 5 weeks old. Meanwhile, a nitric oxide synthase inhibitor, N (gamma)-nitro-L-arginine methyl ester (L-NAME) (N5751, Sigma) was supplied in drinking water (0.5 g/L) for HFpEF groups, and the pH of the drinking water was adjusted to 7.4. The above placebo solvent was administrated in the same manner. (3) The HFpEF + Levo group (n = 16): according to the previous study, HFpEF mice received 3 mg/kg levosimendan (S2446, Selleck) (Dissolve 1 mg of levosimendan in 50 uL of DMSO, subsequently dilute to 1 mg/mL with the above solvent) intraperitoneally once a week from week 13 to 17. REF000975 ICD-11: BD11 Left ventricular failure CELL10171 Heart tissues Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00749 Levosimendan reversed mitochondrial malfunction in heart failure with preserved ejection fraction (HFpEF) mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. Levosimendan reverses cardiac malfunction and cardiomyocyte ferroptosis during heart failure with preserved ejection fraction via connexin 43 signaling activation. Suppressor . Up regulation . . Suppressor We purchased forty-eight 3-week-old male C57BL/6N mice from Beijing HFK Bioscience Co. Ltd. and gave a twelve-hour light and dark cycle starting from 06:00 (am) to 18:00 (pm). Mice were randomly assigned into three groups after 2 weeks of adaptive feeding as follows. (1) The control group (n = 16): mice were provided with normal drinking water, a normal diet and intraperitoneal administration of solvent (5% DMSO + 40% Peg300 + 5% Tween 80 + 50% ddH2O) 3 mL/kg once a week aged 13 to 17 weeks. (2) The HFpEF group (n = 16): a double-hit model was designed, in which metabolic and mechanical stress worked together and resulted in HFpEF. Briefly, C57BL/6N mice had unrestricted access to a high-fat diet (HFD, D12492, Research Diet) starting from 5 weeks old. Meanwhile, a nitric oxide synthase inhibitor, N (gamma)-nitro-L-arginine methyl ester (L-NAME) (N5751, Sigma) was supplied in drinking water (0.5 g/L) for HFpEF groups, and the pH of the drinking water was adjusted to 7.4. The above placebo solvent was administrated in the same manner. (3) The HFpEF + Levo group (n = 16): according to the previous study, HFpEF mice received 3 mg/kg levosimendan (S2446, Selleck) (Dissolve 1 mg of levosimendan in 50 uL of DMSO, subsequently dilute to 1 mg/mL with the above solvent) intraperitoneally once a week from week 13 to 17. REF000975 ICD-11: BD11 Left ventricular failure CELL10171 Heart tissues Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00747 Levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels. Levosimendan Reverses Cardiac Malfunction and Cardiomyocyte Ferroptosis During Heart Failure with Preserved Ejection Fraction via Connexin 43 Signaling Activation. Suppressor Up regulation . . Suppressor . We purchased forty-eight 3-week-old male C57BL/6N mice from Beijing HFK Bioscience Co. Ltd. and gave a twelve-hour light and dark cycle starting from 06:00 (am) to 18:00 (pm). Mice were randomly assigned into three groups after 2 weeks of adaptive feeding as follows. (1) The control group (n = 16): mice were provided with normal drinking water, a normal diet and intraperitoneal administration of solvent (5% DMSO + 40% Peg300 + 5% Tween 80 + 50% ddH2O) 3 mL/kg once a week aged 13 to 17 weeks. (2) The HFpEF group (n = 16): a double-hit model was designed, in which metabolic and mechanical stress worked together and resulted in HFpEF. Briefly, C57BL/6N mice had unrestricted access to a high-fat diet (HFD, D12492, Research Diet) starting from 5 weeks old. Meanwhile, a nitric oxide synthase inhibitor, N (gamma)-nitro-L-arginine methyl ester (L-NAME) (N5751, Sigma) was supplied in drinking water (0.5 g/L) for HFpEF groups, and the pH of the drinking water was adjusted to 7.4. The above placebo solvent was administrated in the same manner. (3) The HFpEF + Levo group (n = 16): according to the previous study, HFpEF mice received 3 mg/kg levosimendan (S2446, Selleck) (Dissolve 1 mg of levosimendan in 50 uL of DMSO, subsequently dilute to 1 mg/mL with the above solvent) intraperitoneally once a week from week 13 to 17. REF000975 ICD-11: BD11 Left ventricular failure CELL10171 Heart tissues Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01436 MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for atherosclerosis. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001). . . . Down regulation Driver Suppressor . REF000678 ICD-11: BD40 Atherosclerosis CELL10037 HUVECs Ferroptosis (hsa04216) Cell ferroptosis
unique01437 MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for atherosclerosis. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001). . . . Up regulation Driver Driver . REF000678 ICD-11: BD40 Atherosclerosis CELL10037 HUVECs Ferroptosis (hsa04216) Cell ferroptosis
unique01158 Overexpression of PDSS2 suppressed the ferroptosis of HCAECs by promoting the activation of Nrf2 pathways. Thence PDSS2 may play a cardio-protective role in atherosclerosis (AS). . . . Up regulation Suppressor Marker/Suppressor Eight-week-old male mice PDSS2 wild type [WT (n = 6)], PDSS2/, Nrf2/, Nrf2+/+, on C57BL/6 background (18-22 g) were provided by Nanjing Medical University (Nanjing, China). PDSS2/ mice (n = 12) were crossed with PDSS2/ to obtain PDSS2/, Nrf2/ (n = 6) and PDSS2/, Nrf2+/+ (n = 6) mice. Mice were fed an AIN76A Western diet for 8 weeks to accelerate the development of AS. Mice from each group were euthanized after 8 weeks. REF000395 ICD-11: BD40 Atherosclerosis CELL10057 HCAECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00075 VSMC ferroptosis was induced by acrolein and methyl vinyl ketone, major constituents of CSE. CSE also induced the upregulation of Ptgs2 mRNA, lipid peroxidation, and intracellular GSH depletion, which are key features of ferroptosis. These findings suggest that ferroptosis is a potential therapeutic target for preventing aortic aneurysm and dissection. Inducer . Up regulation . . Marker C57BL/6J wild-type mice (8-10 wk old, male) were purchased from Japan SLC (Tokyo, Japan). Mice were housed (4/cage, RAIR HD-ventilated micro-isolator animal housing systems; Laboratory Products, Seaford, DE) in an environment maintained at 23 ± 2 with ad libitum access to food and water under a 12-h:12-h light-dark cycle, with lights on from 0800 to 2000. A total of 13 mice were used. The aorta was harvested immediately after mice were euthanized by inhalation of carbon dioxide, washed in 0.1% antibiotics/PBS, and cut into 3-4-mm rings. The aortic rings were cultured in 10% FCS/DMEM for 3 h and then treated with CSE (0.8 mg/mL) for the indicated periods. REF000128 ICD-11: BD50 Aortic aneurysm CELL10186; CELL00592; CELL00439; CELL00569 VSMCs; A7r5; EAhy926; 10T1/2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00074 VSMC ferroptosis was induced by acrolein and methyl vinyl ketone, major constituents of CSE. CSE also induced the upregulation of Ptgs2 mRNA, lipid peroxidation, and intracellular GSH depletion, which are key features of ferroptosis. These findings suggest that ferroptosis is a potential therapeutic target for preventing aortic aneurysm and dissection. Inducer . Up regulation . . Marker C57BL/6J wild-type mice (8-10 wk old, male) were purchased from Japan SLC (Tokyo, Japan). Mice were housed (4/cage, RAIR HD-ventilated micro-isolator animal housing systems; Laboratory Products, Seaford, DE) in an environment maintained at 23 ± 2 with ad libitum access to food and water under a 12-h:12-h light-dark cycle, with lights on from 0800 to 2000. A total of 13 mice were used. The aorta was harvested immediately after mice were euthanized by inhalation of carbon dioxide, washed in 0.1% antibiotics/PBS, and cut into 3-4-mm rings. The aortic rings were cultured in 10% FCS/DMEM for 3 h and then treated with CSE (0.8 mg/mL) for the indicated periods. REF000128 ICD-11: BD50 Aortic aneurysm CELL10186; CELL00592; CELL00439; CELL00569 VSMCs; A7r5; EAhy926; 10T1/2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00449 Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Suppressor . Down regulation . . Marker/Suppressor Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. REF000592 ICD-11: BE2Z Cardiovascular diseases CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00428 Astragaloside IV partially upregulated the levels of SLC7A11 and GPX4 expression which were reduced by LPC. The LPC-suppressed proliferation and LPC-induced apoptosis and senescence of endothelial cells were greatly attenuated by AS-IV treatment. In conclusion, AS-IV could serve as a novel drug for treating ferroptosis-related cardiovascular diseases. Suppressor . Up regulation . . Suppressor . REF000576 ICD-11: BE2Z Cardiovascular diseases CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01652 UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/ miR-124/SERTAD4 for cardiovascular diseases. . . . Up regulation Suppressor Suppressor . REF000858 ICD-11: BE2Z Cardiovascular diseases CELL10019 Human aortic advential fibroblasts Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01651 UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/miR-124/SERTAD4 for cardiovascular diseases. . . . Down regulation Driver Suppressor . REF000858 ICD-11: BE2Z Cardiovascular diseases CELL10019 Human aortic advential fibroblasts Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01653 UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/miR-124/ SERTAD4 for cardiovascular diseases. . . . Down regulation Driver Suppressor . REF000858 ICD-11: BE2Z Cardiovascular diseases CELL10019 Human aortic advential fibroblasts Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00448 Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Suppressor . Up regulation . . Marker/Suppressor Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. REF000592 ICD-11: BE2Z Cardiovascular diseases CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00427 Astragaloside IV partially upregulated the levels of SLC7A11 and GPX4 expression which were reduced by LPC. The LPC-suppressed proliferation and LPC-induced apoptosis and senescence of endothelial cells were greatly attenuated by AS-IV treatment. In conclusion, AS-IV could serve as a novel drug for treating ferroptosis-related cardiovascular diseases. Suppressor . Up regulation . . Suppressor . REF000576 ICD-11: BE2Z Cardiovascular diseases CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00446 Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Suppressor . Up regulation . . Suppressor Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. REF000592 ICD-11: BE2Z Cardiovascular diseases CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00447 Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Suppressor . Up regulation . . Marker/Suppressor/Driver Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. REF000592 ICD-11: BE2Z Cardiovascular diseases CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00469 Treatment with DHQ (Taxifolin) significantly reverses the ferroptosis induced by cigarette smoke both in vivo and in vitro via a Nrf2-dependent signaling pathway. These findings may provide novel therapeutic options for the treatment of chronic obstructive pulmonary disease (COPD) patients. Suppressor . Up regulation . . Marker/Suppressor Thirty-two male BALB/c mice (21-25 g, 6-8 weeks) were purchased from Hunan Slyke Jingda Laboratory Animal Co., Ltd. and kept in a clean unit at 23 ± 2 , 50% ± 10% relative humidity and 12 h rhythm of light and dark. Mice were randomly divided into four groups (n = 8 for each group): the control group, cigarette smoke-inducedCOPDgroup, COPD + low dose (50mg/kg/d)DHQgroup, and COPD + high dose (100 mg/kg/d) DHQ group. The mice in the control group were maintained in fresh air and given anintraperitoneal injectionof 0.3 ml/20 g phosphate-buffered saline (PBS) on Days 0, 11, and 23. The COPD mouse model was established as previously described. Mice in this group were exposed to cigarette smoke for 2 cycles per day (1 h per cycle), 6 days per week for 4 consecutive weeks in a sealed box with ventilation holes except for Days 0, 11, and 22, and over these 3 days, the mice were intraperitoneally injected with 0.3 ml/20g 100% CSE. Mice in the COPD+low-dose DHQ group and COPD+high-dose DHQ group were treated with cigarette smoke and 100% CSE as mentioned above and intraperitoneally injected with DHQ for 25 consecutive days except for Days 0, 11, and 22, while mice in the control and COPD groups were intraperitoneally injected with an equal volume of PBS except for Days 0, 11, and 22. All mice were sacrificed by intraperitoneal injection of 0.5 ml 3% chloral hydrateon the 29 th day of the experiment. REF000621 ICD-11: CA22 Chronic obstructive pulmonary disease CELL00085 HBE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00316 Bleomycin (BLM) can induce the inhibition of cellular GPX4, leading to the generation of lipid ROS. Besides, BLM treatment significantly increased the expression levels of ACSL4 but similarly decreased those of FSP1. TfR1 expression was significantly increased by BLM treatment but decreased by BLM + DFO treatment. These findings indicate that iron metabolism disorder, iron deposition, and ferroptosis in ATII cells may be involved in the pathogenesis of BLM-induced pulmonary fibrosis. Inducer . Up regulation . . Driver C57BL/6 J mice (8-week old) from SLAC Laboratory Animal Co. LTD (Shanghai, China) were housed in a specific pathogen-free (SPF) barrier system at 20 with 12-h light/dark cycles. They were randomly grouped as follows: (1) intratracheal saline (control group); (2) intraperitoneal deferoxamine (DFO, Sigma-Aldrich; DFO group); (3) intratracheal bleomycin (BLM, Nippon Kayaku Co., Ltd.; BLM group); and (4) intratracheal BLM plus intraperitoneal deferoxamine (BLM + DFO group). They were intratracheally injected with 50 ul of BLM (5 mg/kg) on day 0. For the preventive anti-fibrotic treatment, DFO (50 mg/kg2 day-1) was administered from day 0 to day 20. Lung samples were collected at day 21. REF000440 ICD-11: CB03 Pulmonary fibrosis CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00315 Bleomycin (BLM) can induce the inhibition of cellular GPX4, leading to the generation of lipid ROS. Besides, BLM treatment significantly increased the expression levels of TfR1 and DMT1 in a concentration- and time-dependent manner but similarly decreased those of FPN. TfR1 expression was significantly increased by BLM treatment but decreased by BLM + DFO treatment. These findings indicate that iron metabolism disorder, iron deposition, and ferroptosis in ATII cells may be involved in the pathogenesis of BLM-induced pulmonary fibrosis. Inducer . Up regulation . . Driver C57BL/6 J mice (8-week old) from SLAC Laboratory Animal Co. LTD (Shanghai, China) were housed in a specific pathogen-free (SPF) barrier system at 20 with 12-h light/dark cycles. They were randomly grouped as follows: (1) intratracheal saline (control group); (2) intraperitoneal deferoxamine (DFO, Sigma-Aldrich; DFO group); (3) intratracheal bleomycin (BLM, Nippon Kayaku Co., Ltd.; BLM group); and (4) intratracheal BLM plus intraperitoneal deferoxamine (BLM + DFO group). They were intratracheally injected with 50 ul of BLM (5 mg/kg) on day 0. For the preventive anti-fibrotic treatment, DFO (50 mg/kg2 day-1) was administered from day 0 to day 20. Lung samples were collected at day 21. REF000440 ICD-11: CB03 Pulmonary fibrosis CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00986 Inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and pulmonary fibrosis (PF) development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. . . . Up regulation Driver Driver Male Sprague-Dawley rats (200-220 g) were purchased from Weitonglihua Company (Beijing, China) and maintained in a pathogen-free facility. After one week of adaptive feeding, a total of 30 rats were randomly divided into 3 groups (n = 10 rats/group): a control group; bleomycin (BLM) group; and BLM + sh-ZFAS1 group. Rats in the BLM group were administered 5 mg/kg BLM (Nippon Kayaku, Japan) dissolved in phosphate buffered saline (PBS) and administered to the rats intratracheally to establish the PF model. Rats in the control group were treated with 0.05 mL PBS. Rats in the BLM + sh-ZFAS1 group were injected intraperitoneally with 30 uL lncRNA ZFAS1 shRNA adeno-associated virus 5 (Vigene Biosciences, USA) for 3 weeks prior to an injection of 5 mg/kg BLM sulfate. REF000180 ICD-11: CB03 Chronic obstructive pulmonary disease complicated with atherosclerosis CELL00092 HFL1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique00987 Inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and pulmonary fibrosis (PF) development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. . . . Down regulation Suppressor Driver Male Sprague-Dawley rats (200-220 g) were purchased from Weitonglihua Company (Beijing, China) and maintained in a pathogen-free facility. After one week of adaptive feeding, a total of 30 rats were randomly divided into 3 groups (n = 10 rats/group): a control group; bleomycin (BLM) group; and BLM + sh-ZFAS1 group. Rats in the BLM group were administered 5 mg/kg BLM (Nippon Kayaku, Japan) dissolved in phosphate buffered saline (PBS) and administered to the rats intratracheally to establish the PF model. Rats in the control group were treated with 0.05 mL PBS. Rats in the BLM + sh-ZFAS1 group were injected intraperitoneally with 30 uL lncRNA ZFAS1 shRNA adeno-associated virus 5 (Vigene Biosciences, USA) for 3 weeks prior to an injection of 5 mg/kg BLM sulfate. REF000180 ICD-11: CB03 Chronic obstructive pulmonary disease complicated with atherosclerosis CELL00092 HFL1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique00318 Bleomycin (BLM) can induce the inhibition of cellular GPX4, leading to the generation of lipid ROS. Besides, BLM treatment significantly increased the expression levels of TfR1 and DMT1 in a concentration- and time-dependent manner but similarly decreased those of FPN. TfR1 expression was significantly increased by BLM treatment but decreased by BLM + DFO treatment. These findings indicate that iron metabolism disorder, iron deposition, and ferroptosis in ATII cells may be involved in the pathogenesis of BLM-induced pulmonary fibrosis. Inducer . Down regulation . . Marker/Suppressor C57BL/6 J mice (8-week old) from SLAC Laboratory Animal Co. LTD (Shanghai, China) were housed in a specific pathogen-free (SPF) barrier system at 20 with 12-h light/dark cycles. They were randomly grouped as follows: (1) intratracheal saline (control group); (2) intraperitoneal deferoxamine (DFO, Sigma-Aldrich; DFO group); (3) intratracheal bleomycin (BLM, Nippon Kayaku Co., Ltd.; BLM group); and (4) intratracheal BLM plus intraperitoneal deferoxamine (BLM + DFO group). They were intratracheally injected with 50 ul of BLM (5 mg/kg) on day 0. For the preventive anti-fibrotic treatment, DFO (50 mg/kg2 day-1) was administered from day 0 to day 20. Lung samples were collected at day 21. REF000440 ICD-11: CB03 Pulmonary fibrosis CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00314 Bleomycin (BLM) can induce the inhibition of cellular GPX4, leading to the generation of lipid ROS. Besides, BLM treatment significantly increased the expression levels of ACSL4 but similarly decreased those of FSP1. TfR1 expression was significantly increased by BLM treatment but decreased by BLM + DFO treatment. These findings indicate that iron metabolism disorder, iron deposition, and ferroptosis in ATII cells may be involved in the pathogenesis of BLM-induced pulmonary fibrosis. Inducer . Up regulation . . Marker/Suppressor/Driver C57BL/6 J mice (8-week old) from SLAC Laboratory Animal Co. LTD (Shanghai, China) were housed in a specific pathogen-free (SPF) barrier system at 20 with 12-h light/dark cycles. They were randomly grouped as follows: (1) intratracheal saline (control group); (2) intraperitoneal deferoxamine (DFO, Sigma-Aldrich; DFO group); (3) intratracheal bleomycin (BLM, Nippon Kayaku Co., Ltd.; BLM group); and (4) intratracheal BLM plus intraperitoneal deferoxamine (BLM + DFO group). They were intratracheally injected with 50 ul of BLM (5 mg/kg) on day 0. For the preventive anti-fibrotic treatment, DFO (50 mg/kg2 day-1) was administered from day 0 to day 20. Lung samples were collected at day 21. REF000440 ICD-11: CB03 Pulmonary fibrosis CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00317 Bleomycin (BLM) can induce the inhibition of cellular GPX4, leading to the generation of lipid ROS. Besides, BLM treatment significantly increased the expression levels of ACSL4 but similarly decreased those of FSP1. TfR1 expression was significantly increased by BLM treatment but decreased by BLM + DFO treatment. These findings indicate that iron metabolism disorder, iron deposition, and ferroptosis in ATII cells may be involved in the pathogenesis of BLM-induced pulmonary fibrosis. Inducer . Down regulation . . Suppressor C57BL/6 J mice (8-week old) from SLAC Laboratory Animal Co. LTD (Shanghai, China) were housed in a specific pathogen-free (SPF) barrier system at 20 with 12-h light/dark cycles. They were randomly grouped as follows: (1) intratracheal saline (control group); (2) intraperitoneal deferoxamine (DFO, Sigma-Aldrich; DFO group); (3) intratracheal bleomycin (BLM, Nippon Kayaku Co., Ltd.; BLM group); and (4) intratracheal BLM plus intraperitoneal deferoxamine (BLM + DFO group). They were intratracheally injected with 50 ul of BLM (5 mg/kg) on day 0. For the preventive anti-fibrotic treatment, DFO (50 mg/kg2 day-1) was administered from day 0 to day 20. Lung samples were collected at day 21. REF000440 ICD-11: CB03 Pulmonary fibrosis CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00222 Periodontitis-level butyrate disrupted iron homeostasis by activation of NCOA4-mediated ferritinophagy, leading to ferroptosis in PDLFs. Butyrate-induced iron accumulation, reactive oxygen species (ROS) generation, glutathione depletion and lipid peroxidation in PDLFs, and the butyrate-induced ferroptosis can be blocked by the lipid peroxide scavenger ferrostatin-1. Inducer . Up regulation . . Driver . REF000283 ICD-11: DA0C Periodontitis CELL10092 PDLFs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique01527 Inhibition of LINC00616 promoted cell viability and suppressed ferroptosis of PDLSCs. miR-370 was verified to be a target of LINC00616. Additionally, miR-370 targeting the transferrin receptor protein and upregulated transferrin receptor (TFRC) abolished the effects of overexpressed miR-370 on cell viability and ferroptosis of PDLSCs. Therefore, LINC00616 knockdown may be a promising therapeutic strategy for periodontitis. . . . Up regulation Driver Marker/Suppressor/Driver . REF000746 ICD-11: DA0C Periodontitis CELL10044 Periodontal ligament stem cell Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01528 Inhibition of LINC00616 promoted cell viability and suppressed ferroptosis of PDLSCs. miR-370 was verified to be a target of LINC00616. Additionally, miR-370 targeting the transferrin receptor protein and upregulated transferrin receptor (TFRC) abolished the effects of overexpressed miR-370 on cell viability and ferroptosis of PDLSCs. Therefore, LINC00616 knockdown may be a promising therapeutic strategy for periodontitis. . . . Down regulation Suppressor Marker/Suppressor/Driver . REF000746 ICD-11: DA0C Periodontitis CELL10044 Periodontal ligament stem cell Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00048 The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased. Suppressor . Up regulation . . Marker/Suppressor In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model. REF000097 ICD-11: DB91 Acute liver failure CELL00304 L02 Ferroptosis (hsa04216) Cell ferroptosis
unique01280 HBx facilitates ferroptosis in acute liver failure (ALF) via EZH2/H3K27me3-mediated SLC7A11 suppression. . . . Down regulation Driver Suppressor Male C57BL/6 mice (n = 20, 6-8-week-old, b.w. 18-23 g) were purchased from SJA Laboratory Animal Co Ltd., Changsha, Hunan, China. Mice were given 600 mg/kg D-GalN (Sigma-Aldrich) and 30 ug/kg LPS (Sigma-Aldrich) by intraperitoneal injection. Mice in Sham group were received saline injection. For Fer-1 treatment, mice were received 10 mg/kg Fer-1 at 1 h prior to D-GalN and LPS injection. The wild-type (WT) or HBx-Tg mice were then subjected to D-GalN and LPS administration. For GSK126 treatment, wild-type (WT) or HBx-Tg mice were received GSK126 (150 mg/kg) prior to D-GalN and LPS administration. REF000531 ICD-11: DB91 Acute liver failure CELL10040; CELL10142 Liver tissues; Primary hepatocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00047 The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased. Suppressor Down regulation . . Driver . In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model. REF000097 ICD-11: DB91 Acute liver failure CELL00304 L02 Ferroptosis (hsa04216) Cell ferroptosis
unique00785 Epigallocatechin-3-Gallate (EGCG) supplementation and Fer-1 treatment apparently increased the protein expression of GPX4 and markedly decreased the protein expression of COX-2 and ACSL4 in the livers of HFD-fed mice. Epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes. Suppressor . Down regulation . . Driver After adaptive feeding, mice were randomly assigned to five groups (n = 10 per group). The details of the groups are as follows: 1) the normal diet (ND) group in which mice were fed ND (18% calories from fat); 2) the HFD group in which mice were fed HFD (60% calories from fat); 3) the HFD-EGCG/L group in which mice received 20 mg/kgbw EGCG by oral gavage daily during HFD feeding; 4) the HFD-EGCG/H group in which mice received 100 mg/kgbw EGCG by oral gavage daily during HFD feeding; and 5) the HFD-Fer-1 group in which mice received intraperitoneal injection of Fer-1 at 1 mg/kg. bw every 3 days during HFD feeding. Mice in the EGCG treatment groups were supplemented with EGCG (20 and 100 mg/kgbw) for 12 weeks. Meanwhile, mice in the ND group and the HFD group were orally gavaged with deionized water daily. REF001003 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00304 L-02 Ferroptosis (hsa04216) Cell ferroptosis
unique01171 ENO3 promoted the progression of NASH by negatively regulating ferroptosis via elevating GPX4 expression and lipid accumulation. These findings provided solid foundation for the mechanism of ferroptosis on the progression of NASH regulated by ENO3, suggesting that ENO3 may be a potential therapeutic target for non-alcoholic fatty liver disease. . . . Up regulation Suppressor Marker/Suppressor Eight-week-old C57BL/6 mice, body weight about 22-24 g, male (n = 24) were purchased from Beijing Vital River Laboratory Animal Technology Co. Ltd China. The mice were randomly divided into four groups and were maintained on a MCD diet (Medicience, Yangzhou, China) for 4, 8, and 12 weeks to induce NASH. Liver tissue and blood samples (from the eyeballs of the mice) were harvested for further analyses. Mice on a normal diet were used as the control. REF000406 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00304 L02 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00784 Epigallocatechin-3-Gallate (EGCG) supplementation and Fer-1 treatment apparently increased the protein expression of GPX4 and markedly decreased the protein expression of COX-2 and ACSL4 in the livers of HFD-fed mice. Epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes. Suppressor . Up regulation . . Suppressor After adaptive feeding, mice were randomly assigned to five groups (n = 10 per group). The details of the groups are as follows: 1) the normal diet (ND) group in which mice were fed ND (18% calories from fat); 2) the HFD group in which mice were fed HFD (60% calories from fat); 3) the HFD-EGCG/L group in which mice received 20 mg/kgbw EGCG by oral gavage daily during HFD feeding; 4) the HFD-EGCG/H group in which mice received 100 mg/kgbw EGCG by oral gavage daily during HFD feeding; and 5) the HFD-Fer-1 group in which mice received intraperitoneal injection of Fer-1 at 1 mg/kg. bw every 3 days during HFD feeding. Mice in the EGCG treatment groups were supplemented with EGCG (20 and 100 mg/kgbw) for 12 weeks. Meanwhile, mice in the ND group and the HFD group were orally gavaged with deionized water daily. REF001003 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00304 L-02 Ferroptosis (hsa04216) Cell ferroptosis
unique01140 GPX4, a crucial regulator of ferroptosis, were upregulated in the livers of the ECH1-overexpressing mice. ECH1 knockdown exacerbated nonalcoholic steatohepatitis (NASH) progression, but this phenomenon was reversed through ferroptosis inhibition. . . . Up regulation Suppressor Suppressor Six-week-old male C57BL/6 mice were purchased from the Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). All of the mice were fed either a standard chow diet (SCD) (containing 62.2% carbohydrate, 24.6% protein, and 13.2% fat) or only a methionine-choline deficient diet (MCD) (containing 20% carbohydrate, 20% protein, and 60% fat) for 8 wk. REF000373 ICD-11: DB92 Nonalcoholic steatohepatitis CELL10040; CELL00057 Liver tissues; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01199 T4 ( TMSB4X and TMSB4Y) protects hepatocytes by inhibiting the GPX4-mediated ferroptosis pathway, which provides a new strategy and target for the treatment of non-alcoholic fatty liver disease (NAFLD). . . . Up regulation Suppressor Suppressor The 42 Specified Pathogen Free (SPF)-grade Sprague Dawley (SD) male rats with weighing (180 ± 20) g were purchased from Changsha Tianqin Experimental Animal Center. All rat were randomly divided into seven groups (6 rat per group) using a random number table. Rats were deeply anesthetized with chloral hydrate (0.5 ml/kg) and killed at the end of the experiment, after 8 weeks of modeling and 4 weeks of drug treatment. REF000455 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00304 LO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01200 T4 (TMSB4X and TMSB4Y) protects hepatocytes by inhibiting the GPX4-mediated ferroptosis pathway, which provides a new strategy and target for the treatment of non-alcoholic fatty liver disease (NAFLD). . . . Up regulation Suppressor Suppressor The 42 Specified Pathogen Free (SPF)-grade Sprague Dawley (SD) male rats with weighing (180 ± 20) g were purchased from Changsha Tianqin Experimental Animal Center. All rat were randomly divided into seven groups (6 rat per group) using a random number table. Rats were deeply anesthetized with chloral hydrate (0.5 ml/kg) and killed at the end of the experiment, after 8 weeks of modeling and 4 weeks of drug treatment. REF000455 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00304 LO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00180 Ginkgolide B (GB), a main constituent of Ginkgo biloba extracts, reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease (NAFLD) in obese mice. Remarkably, after Nrf2 interference, GB treatment significantly increased Nrf2 expression, indicating that GB exerted anti-ferroptosis effects by activation of Nrf2 pathway. Suppressor . Up regulation . . Marker/Suppressor Male 8-week-old C57/BL6 ApoE-/-mice of weight (22~25 g) were purchased from Changzhou Cavens experimental animal Co., Ltd (Jiangsu, China). After 5 weeks of feeding, HFD-fed mice were randomly assigned into 4 groups (n = 10) : HFD group (0.9 % sodium chloride by gavage), GB-L group (at a high dose of 20 mg kg-1d-1 GB in 0.9 % sodium chloride by gavage), GB-H group (at a high dose of 30 mg kg-1d-1 GB in 0.9 % sodium chloride by gavage), and Ato group (1.3 mg kg-1d-1 Ato in 0.9 % sodium chloride by gavage) as a positive control. The mice in ND group were given the same volume of 0.9 % sodium chloride. REF000238 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00048 HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00786 Epigallocatechin-3-Gallate (EGCG) supplementation and Fer-1 treatment apparently increased the protein expression of GPX4 and markedly decreased the protein expression of COX-2 and ACSL4 in the livers of HFD-fed mice. Epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes. Suppressor Down regulation . . . Driver After adaptive feeding, mice were randomly assigned to five groups (n = 10 per group). The details of the groups are as follows: 1) the normal diet (ND) group in which mice were fed ND (18% calories from fat); 2) the HFD group in which mice were fed HFD (60% calories from fat); 3) the HFD-EGCG/L group in which mice received 20 mg/kgbw EGCG by oral gavage daily during HFD feeding; 4) the HFD-EGCG/H group in which mice received 100 mg/kgbw EGCG by oral gavage daily during HFD feeding; and 5) the HFD-Fer-1 group in which mice received intraperitoneal injection of Fer-1 at 1 mg/kg. bw every 3 days during HFD feeding. Mice in the EGCG treatment groups were supplemented with EGCG (20 and 100 mg/kgbw) for 12 weeks. Meanwhile, mice in the ND group and the HFD group were orally gavaged with deionized water daily. REF001003 ICD-11: DB92 Non-alcoholic fatty liver disease CELL00304 L-02 Ferroptosis (hsa04216) Cell ferroptosis
unique00391 m6A reader YTHDF1 promoted BECN1 mRNA stability via recognizing the m6A binding site, thus triggering autophagy activation, and eventually leading to HSC ferroptosis. FTO plasmid and METTL4 shRNA markedly impaired erastin-induced upregulation of NCOA4 and downregulation of FTH1 in HSC-LX2 cells. Overall, m6A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis. . . . Up regulation Driver Driver ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports. REF000525 ICD-11: DB93 Liver fibrosis CELL10073 HSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00389 m6A reader YTHDF1 promoted BECN1 mRNA stability via recognizing the m6A binding site, thus triggering autophagy activation, and eventually leading to HSC ferroptosis. FTO plasmid and METTL4 shRNA markedly impaired erastin-induced upregulation of NCOA4 and downregulation of FTH1 in HSC-LX2 cells. Overall, m6A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis. . . . Up regulation Suppressor Marker/Suppressor ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports. REF000525 ICD-11: DB93 Liver fibrosis CELL10073 HSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00163 Chrysophanol significantly induced HBx-transfected HSC-T6 death by inducing ferroptosis, as demonstrated by lipid ROS accumulation and upregulation of expression of ER markers, such as Bip, CHOP, and p-IRE1, and ferroptotic markers, such as GPX4 and SLC7A11. Therefore, chrysophanol may exert ferroptotic effects on activated HSCs to prevent liver fibrosis. Inducer . Down regulation . . Suppressor . REF000218 ICD-11: DB93 Liver fibrosis CELL00594 HSC-T6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00177 ART (artemether) could lead to the accumulation of IRP2 a in hepatic stellate cell by inhibiting the ubiquitination of it, thus inducing the increase of iron in HSC (hepatic stellate cell), which could product a large number of ROS (reactive oxide species), resulting the occurrence of ferroptosis in cells. The findings provided an experimental basis for ART to become a drug for the treatment of liver fibrosis. Inducer . Up regulation . . Driver The animal experiment scheme was approved by the institution of Nanjing University ofChinese Medicine (Nanjing, China) and the local animal protection and utilization committee. After the last administration, diet was prohibited, but drinking water was not restricted. 24 h later, the mice were weighed and taken blood. REF000235 ICD-11: DB93 Liver fibrosis CELL10073; CELL00594; CELL00508; CELL00048 HSC-LX2; HSC-T6; LO-2; HepG2 Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00390 m6A reader YTHDF1 promoted BECN1 mRNA stability via recognizing the m6A binding site, thus triggering autophagy activation, and eventually leading to HSC ferroptosis. FTO plasmid and METTL4 shRNA markedly impaired erastin-induced upregulation of NCOA4 and downregulation of FTH1 in HSC-LX2 cells. Overall, m6A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis. . . . Down regulation Suppressor Driver ICR mice (8-week-old, 18-22 g) were obtained from Yangzhou University (Yangzhou, China). There were 8 mice in each group and they were randomly divided into 6 groups. Mice were treated with Vehicle, CCl4, VA-Lip-control-vector+CCl4+Erastin, VA-Lip-Mettl4-shRNA+CCl4+Erastin, VA-Lip-Fto-plasmid+CCl4+Erastin, VA-Lip- Ythdf1-shRNA+CCl4+Erastin, respectively. A mixture of olive oil and carbon tetrachloride (CCl4) (9:1 (v/v)) was used to trigger liver fibrosis in mouse model by intraperitoneal injection (0.1 ml/20 g body weight), according to our previous reports. REF000525 ICD-11: DB93 Liver fibrosis CELL10073 HSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01017 BRD7-P53-SLC25A28 axis involves in mediating ferroptosis via mitochondrial iron metabolism pathway. These findings reveal novel signal transduction and regulatory mechanism of ferroptosis, and also suggest BRD7-P53-SLC25A28 axis as potential targets for liver fibrosis. . . . Up regulation Driver Driver Eight-week-old male C57BL/6 mice were purchased from Nanjing Medical University (Nanjing, China). Sixty mice were randomly divided into six groups of ten animals each with comparable mean body weight. Mice of six groups were treated with Sham, BDL + VA-Lip-Control-shRNA, BDL + VA-Lip-Control-shRNA + erastin, BDL + VA-Lip-BRD7-shRNA + erastin, BDL + VA-Lip-P53-shRNA + erastin or BDL + VA-Lip-SLC25A28-shRNA + erastin, respectively. Mice were anesthetized with isoflurane. A midline laparotomy was performed, and the common bile duct was ligated close to the liver hilus immediately below the bifurcation with 3-0 surgical silk and cut between the ligatures as described previously. REF000223 ICD-11: DB93 Liver fibrosis CELL10073; CELL00594 HSC-LX2; HSC-T6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01018 BRD7-P53-SLC25A28 axis involves in mediating ferroptosis via mitochondrial iron metabolism pathway. These findings reveal novel signal transduction and regulatory mechanism of ferroptosis, and also suggest BRD7-P53-SLC25A28 axis as potential targets for liver fibrosis. . . . Up regulation Driver Driver Eight-week-old male C57BL/6 mice were purchased from Nanjing Medical University (Nanjing, China). Sixty mice were randomly divided into six groups of ten animals each with comparable mean body weight. Mice of six groups were treated with Sham, BDL + VA-Lip-Control-shRNA, BDL + VA-Lip-Control-shRNA + erastin, BDL + VA-Lip-BRD7-shRNA + erastin, BDL + VA-Lip-P53-shRNA + erastin or BDL + VA-Lip-SLC25A28-shRNA + erastin, respectively. Mice were anesthetized with isoflurane. A midline laparotomy was performed, and the common bile duct was ligated close to the liver hilus immediately below the bifurcation with 3-0 surgical silk and cut between the ligatures as described previously. REF000223 ICD-11: DB93 Liver fibrosis CELL10073; CELL00594 HSC-LX2; HSC-T6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
dupunique01017 BRD7- P53-SLC25A28 axis involves in mediating ferroptosis via mitochondrial iron metabolism pathway. These findings reveal novel signal transduction and regulatory mechanism of ferroptosis, and also suggest BRD7- P53-SLC25A28 axis as potential targets for liver fibrosis. . . . Up regulation Driver Driver Eight-week-old male C57BL/6 mice were purchased from Nanjing Medical University (Nanjing, China). Sixty mice were randomly divided into six groups of ten animals each with comparable mean body weight. Mice of six groups were treated with Sham, BDL + VA-Lip-Control-shRNA, BDL + VA-Lip-Control-shRNA + erastin, BDL + VA-Lip-BRD7-shRNA + erastin, BDL + VA-Lip-P53-shRNA + erastin or BDL + VA-Lip-SLC25A28-shRNA + erastin, respectively. Mice were anesthetized with isoflurane. A midline laparotomy was performed, and the common bile duct was ligated close to the liver hilus immediately below the bifurcation with 3-0 surgical silk and cut between the ligatures as described previously. REF000223 ICD-11: DB93 Liver fibrosis CELL10073; CELL00594 HSC-LX2; HSC-T6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01151 TRIM26 promotes HSCs ferroptosis to suppress liver fibrosis through mediating the ubiquitination of SLC7A11. The TRIM26-targeted SLC7A11 suppression can be a novel therapeutic strategy for liver fibrosis. . . . Down regulation Driver Suppressor A total of 24 C57BL/6 mice were obtained from the Sippr-BK laboratory animal Co., Ltd. (Shanghai, China). They were randomly divided into four groups: Group I, Vehicle (control); Group II, CCl4; Group III, CCL4 + Vector; Group IV, CCL4 + oeTRIM26. Liver fibrosis was induced in Groups II - IV, by intraperitoneally injecting 50% carbon tetrachloride (CCl4) in corn oil (0.1 mL/100 g body weight) over 8 weeks (3 times/week); control mice were injected with corn oil only. Then, recombinant adenovirus Vector or oeTRIM26 (5 x 109 pfu/mouse, 0.5 mL) was injected into the mice of Group III or IV, respectively, through the tail vein. REF000386 ICD-11: DB93 Liver fibrosis CELL00466 LX-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00164 Chrysophanol significantly induced HBx-transfected HSC-T6 death by inducing ferroptosis, as demonstrated by lipid ROS accumulation and upregulation of expression of ER markers, such as Bip, CHOP, and p-IRE1, and ferroptotic markers, such as GPX4 and SLC7A11. Therefore, chrysophanol may exert ferroptotic effects on activated HSCs to prevent liver fibrosis. Inducer . Down regulation . . Suppressor . REF000218 ICD-11: DB93 Liver fibrosis CELL00594 HSC-T6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01383 Exosomes derived from HBV-infected LO2 cells promote LX-2 cell activation and liver fibrosis in mouse Exosomal miR-222 derived from HBV-infected LO2 cells promotes LX-2 cell activation TFRC is a target of miR-222 and inhibits LX-2 cell activation induced by miR-222 miR-222 promotes LX-2 cell activation through inhibiting TFRC-induced ferroptosis. . . . Down regulation Suppressor Marker/Suppressor/Driver Male C57BL/6 mice (6-8-weeks old; Vitalriver, Beijing, China) were employed. Briefly, 200 ul AAV8-HBV-1.2 was introduced through the tail vein. The exosomes (10 ug) derived from HBV-infected LO2 cells were dissolved in PBS (50 ul) and introduced through the tail vein 2 h after AAV8-HBV-1.2 injection. Mice were anesthetized by inhalation with 3% isoflurane and sacrificed by cervical dislocation after 4 weeks to collect livers for hematoxylin-eosin (HE) and Masson's Trichrome staining and measurement of liver injury as previously described. REF000631 ICD-11: DB93 Liver fibrosis CELL00304 LO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00876 Artesunate evidently triggered ferritinophagy accompanied by up-regulation of LC3 (microtubule-associated protein light chain 3), Atg3, Atg5, Atg6/beclin1, Atg12 (autophagy related genes) and down-regulation of p62, FTH1 (ferritin heavy chain), NCOA4 (nuclear receptor co-activator 4) in activated HSCs. These results suggested that ferritinophagy-mediated HSC ferroptosis was responsible for artesunate-induced anti-fibrosis efficacy in liver fibrosis. Inducer Up regulation . . Driver . 6-8-week-old, 20 ± 2 g, male ICR mice, obtained from Nanjing Medical University (Nanjing, China), were randomly divided into five groups (n = 8 per group). Mouse model of chronic liver fibrosis was established by 10% carbon tetrachloride (CCl4, 0.5 ml/100 g body weight) injection. Groups are follows: (1) Control group was intraperitoneally (i.p.) injected with olive oil; (2) Model group was i.p. injected with 10% CCl4 every other day a week for 8 weeks; (3) Low-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 50 mg/kg artesunate for last 4 weeks; (4) Middle-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 100 mg/kg artesunate for last 4 weeks; (5) High-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 200 mg/kg artesunate for last 4 weeks. REF000056 ICD-11: DB93 Liver fibrosis CELL10073; CELL10073 HSC; LX2 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00462 Nickel chloride caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice. Inducer . Down regulation . . Marker/Suppressor Totally 128 7-week-old ICR male mice (22-25 g) were provided by Dashuo Biological Technology (Chengdu, China). The animals were divided into four groups (32 mice per group) randomly. The mice in the three experimental groups were gavage administered with Ni (NiCl2·6H2O) at doses of 7.5, 15, and 30 mg/kg body weight respectively, while those in the control group were given distilled water. The Ni dose adopted here was determined according to the value of median lethal dose (LD50, 306.11 mg/kg) attained in the research on acute oral toxicity of male mice. We selected 1/40, 1/20 and 1/10 LD50 (306.11 mg/kg) of NiCl2 in this study. REF000614 ICD-11: DB95 Ni-induced hepatotoxicity CELL10040 Liver tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00463 Nickel chloride caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice. Inducer . Down regulation . . Suppressor Totally 128 7-week-old ICR male mice (22-25 g) were provided by Dashuo Biological Technology (Chengdu, China). The animals were divided into four groups (32 mice per group) randomly. The mice in the three experimental groups were gavage administered with Ni (NiCl2·6H2O) at doses of 7.5, 15, and 30 mg/kg body weight respectively, while those in the control group were given distilled water. The Ni dose adopted here was determined according to the value of median lethal dose (LD50, 306.11 mg/kg) attained in the research on acute oral toxicity of male mice. We selected 1/40, 1/20 and 1/10 LD50 (306.11 mg/kg) of NiCl2 in this study. REF000614 ICD-11: DB95 Ni-induced hepatotoxicity CELL10040 Liver tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00464 Nickel chloride caused hepatic ferroptosis accompanied by increased iron content in the liver and up-regulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, down-regulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and nuclear receptor coactivator 4 (NCOA4) protein and mRNA expression levels. Altogether, Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice. Inducer . Up regulation . . Marker Totally 128 7-week-old ICR male mice (22-25 g) were provided by Dashuo Biological Technology (Chengdu, China). The animals were divided into four groups (32 mice per group) randomly. The mice in the three experimental groups were gavage administered with Ni (NiCl2·6H2O) at doses of 7.5, 15, and 30 mg/kg body weight respectively, while those in the control group were given distilled water. The Ni dose adopted here was determined according to the value of median lethal dose (LD50, 306.11 mg/kg) attained in the research on acute oral toxicity of male mice. We selected 1/40, 1/20 and 1/10 LD50 (306.11 mg/kg) of NiCl2 in this study. REF000614 ICD-11: DB95 Ni-induced hepatotoxicity CELL10040 Liver tissues Ferroptosis (hsa04216) Cell ferroptosis
unique01731 FGF4 could be an indispensable regulator in the development of ConA-induced autoimmune hepatitis (AIH), with the addition of extra non-mitogenic rFGF4 being conducive to the alleviation of ferroptosis in hepatocytes by upregulating CISD3 levels as well as activating the Nrf2/HO-1 signal pathway. . . . Up regulation Suppressor Driver/Suppressor Six weeks old male C57BL/6 wild-type (WT) mice (20-25 g) were acquired from Zhejiang Vital River Laboratory Animal Technology Co., Ltd. (China). The animals were given an intravenous injection of ConA (15 mg/kg; Sigma-Aldrich) through the tail vein before sacrificing them 18 h later. Other treatment groups involved administering Ferrostatin-1 (Fer-1, 10 mg/kg; MedChemExpress) intraperitoneally, 30 min prior to the ConA injection. REF000952 ICD-11: DB96 Autoimmune hepatitis CELL00541 AML12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01426 LncAABR07025387.1 acts as a competing endogenous RNA during myocardial ischemia/reperfusion injury. Mechanistically, lncAABR07025387.1 negatively regulates miR-205 expression and subsequently upregulates ACSL4-mediated ferroptosis. . . . Up regulation Driver Driver Adult male Sprague Dawley rats (3 months old, 200 g) purchased from the Animal Center of Nanjing University were housed at a controlled temperature of 18-22 and humidity of 50-70% under a 12-h light/dark cycle with free access to food and water. Before the operation, the rats were fasted overnight with free access to water. At the beginning of the operation, the rats were intraperitoneally injected with chloral hydrate (0.5 ml/100 g) for sedation) and 5% additional first dose for unsatisfactory sedation and made to inhale isoflurane for anesthesia. After incising the skin, the muscle was carefully separated layer by layer, and the trachea was exposed and fixed locally with a self-made pull hook. The trachea was then cut with a 10 ml syringe needle. The anesthesia mask was then replaced with the tracheal intubation. The ventilator was connected to the anesthesia machine for isopentane inhalation (2%). The proximal left anterior descending artery (LAD) was ligated using a 6.0 Prolene suture to induce myocardial ischemia. A small semi-cylindrical plastic hose was inserted to the LAD to facilitate the opening of the knot during reperfusion and to reduce the mechanical damage to the heart tissue and blood vessels. About 5 min later, the chest cavity was temporarily closed with a non-damaging hemostatic clip. After 30 min of ischemia, the noninjury hemostatic clip was loosened, the ligation and the protective tube were removed for reperfusion, and the chest was closed. The rats in the sham group underwent the same operation without being subjected to MI/R. REF000668 ICD-11: DB98 Myocardial ischemia/reperfusion CELL00030; CELL00057 H9C2; HEK293T Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00700 Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA. Suppressor . Down regulation . . Driver In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use. REF000919 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00283 Baicalin prevents against myocardial ischemia/reperfusion injury via suppressing ACSL4-controlled ferroptosis. In addition, enhanced lipid peroxidation and significant iron accumulation along with activated transferrin receptor protein 1 (TfR1) signal and nuclear receptor coactivator 4 (NCOA4)-medicated ferritinophagy were observed in in vivo and in vitro models, which were reversed by baicalin treatment. Suppressor . Down regulation . . Driver Male Sprague-Dawley rats, 260-280 g, were provided by Beijing Vital River Laboratory Animal Technology CO., Ltd. (Beijing, China). Rats were randomly divided into five groups (n = 15 per group): control (sham operation + saline), I/R (I/R + saline), baicalin 100 mg/kg (BA-100, I/R + baicalin 100 mg/kg), baicalin 200 mg/kg (BA-200, I/R + baicalin 200 mg/kg), and diltiazem 20 mg/kg (DI-20, I/R + diltiazem 20 mg/kg). Drugs were given by oral gavage once daily (8 a.m.) for 6 days. At day 6, myocardial ischemia was induced 1 h after drug was administered. REF000398 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00817 Curcumin attenuates liver, pancreas and cardiac ferroptosis, oxidative stress and injury in ischemia/reperfusion-damaged rats by facilitating ACSL/GPx4 signaling. Suppressor . Down regulation . . Driver Forty female albino Wistar rats weighing 180-220 g were used in the study. Eight rats in each group were randomly assigned to five different groups: Group I (Sham); Group II (IR); Group III (IR + DMSO); Group IV (IR + Curcumin 100 mg/kg); and Group V (IR + 2 ug/kg LoxBlock-1) were determined. The animals were maintained at a temperature of 21 ± 2 and regulated humidity conditions (50 ± 5%) with a twelve-hour light/dark cycle. Throughout the experiment, the animals were fed standard commercial rat pellets and given tap water. All surgical and anesthesia procedures were performed understerile conditions. In addition, in a case of abnormal symptoms, the animals would be removed from the group and sacrificed under deep anesthesia. REF001035 ICD-11: DB98 Ischemia-Reperfusion Injury CELL10040; CELL10174; CELL10171 Liver tissues; Pancreas tissues; Heart tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00450 Gossypol acetic acid significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial ischemia/reperfusion-induced ferroptotic cell death. Suppressor . Down regulation . . Driver A total of 55 adult male Sprague-Dawley rat (350-450 g) were anesthetized with urethane (1.5 g/kg, i.p.), then the hearts were perfused in a Langendorff system. After 30 min of stabilization, hearts were subjected to 30 min of global no-flow ischemia by stopping the perfusion. Reperfusion was followed with Krebs Henseleit (KH) buffer and GAA together for 2 h. A thermoregulated chamber kept the heart at 37 throughout the experiment. Control hearts were not subjected to I/R. The heart slices were sectioned at a thickness of 2 mm and stained with triphenyltetrazolium chloride (25 mg/100 mL) for 10 min and then fixed with 4% formaldehyde solution for 48 h to enhance color contrast. REF000593 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00490 Xanthohumol can prevent ferroptosis during cardiac ischemia-reperfusion by reducing the expression of Acsl4 and Ptgs2 mRNA, reducing the expression of ACSL4 and NRF2 protein, and modulating the expression of GPX4 protein. Suppressor . Down regulation . . Driver Rats were anesthetized with urethane (1.5 g/kg, i.p.), then hearts were excised and arrested in Krebs Henseleit (KH) buffer as previously described. Following 30 min equilibration, ischemia was induced by halting perfusion for 45 min. Reperfusion was followed with KH buffer and XN (5 or 10 uM) together for 60 min. Control hearts were not subjected to I/R. REF000654 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00697 Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA. Suppressor . Down regulation . . Driver In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use. REF000919 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00803 Both ferrostain-1 and nobiletin decreased the expression of ferroptosis-related proteins including Acyl-CoA synthetase long chain family member 4 (ACSL4) and nuclear receptor coactivator 4 (NCOA4) but not glutathione peroxidase 4 (GPX4) in rats with mature T2DM and cells with HFHG and H/R injury. Nobiletin has therapeutic potential for alleviating myocardial ischemia-reperfusion injury associated with ACSL4- and NCOA4-related ferroptosis. Suppressor . Down regulation . . Driver Male Sprague-Dawley (SD) rats (4 weeks old, 90-110 g) were obtained from the Vital River Biological company. Rats were kept in a specific-pathogen-free (SPF) environment, with access to food and tap water at an ambient temperature of 20-22 . All institutional and national guidelines for the care and use of laboratory animals were followed. The protocols were reviewed and approved by the Institution of Animal Care and Use Committee of Renmin Hospital of Wuhan University (IACUC, license no. 20200303). REF001020 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01367 Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells. . . . Down regulation Suppressor Driver A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery. REF000623 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00548; CELL10003 HL-1; BMSCs Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01368 Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells. . . . Up regulation Driver Driver A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery. REF000623 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00548; CELL10003 HL-1; BMSCs Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01369 Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/ PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells. . . . Down regulation Suppressor Driver A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery. REF000623 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00548; CELL10003 HL-1; BMSCs Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01575 Human urine-derived stem cells (USCs)-derived exosomes (USC-Exo) could improve kidney ischemia/reperfusion injury (IRI). Mechanistically, LncRNA TUG1 was carried by USC-Exo downregulation of ACSL4 expression in kidney cells by interacting with SRSF1, then inhibited ACSL4-mediated cell ferroptosis, and thus improved kidney injury in IRI-induced AKI. . . . Down regulation Suppressor Driver Mouse renal I/R model was performed in male C57BL/6 mice (8-12 weeks old). Briefly, the mice were anesthetized with pentobarbital sodium by intraperitoneal injection and lay on the right side. Dorsal incisions of both left and right sides were made to expose kidneys. The right kidney artery was gently separated with cotton swabs and occluded with a microvascular clamp to induce renal ischemia for 45 min. The left renal pedicle clamping and ischemia were the same as right. After ischemia, the micro-aneurysm clips were removed to start the reperfusion. The wounds were sutured and resuscitated with warm sterile saline intraperitoneally. All operations were the same in the sham group except for clamping and ischemia. REF000782 ICD-11: DB98 Ischemic/reperfusion injury CELL00093 HK2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01576 Human urine-derived stem cells (USCs)-derived exosomes (USC-Exo) could improve kidney ischemia/reperfusion injury (IRI). Mechanistically, LncRNA TUG1 was carried by USC-Exo downregulation of ACSL4 expression in kidney cells by interacting with SRSF1, then inhibited ACSL4-mediated cell ferroptosis, and thus improved kidney injury in IRI-induced AKI. . . . Down regulation Suppressor Driver Mouse renal I/R model was performed in male C57BL/6 mice (8-12 weeks old). Briefly, the mice were anesthetized with pentobarbital sodium by intraperitoneal injection and lay on the right side. Dorsal incisions of both left and right sides were made to expose kidneys. The right kidney artery was gently separated with cotton swabs and occluded with a microvascular clamp to induce renal ischemia for 45 min. The left renal pedicle clamping and ischemia were the same as right. After ischemia, the micro-aneurysm clips were removed to start the reperfusion. The wounds were sutured and resuscitated with warm sterile saline intraperitoneally. All operations were the same in the sham group except for clamping and ischemia. REF000782 ICD-11: DB98 Ischemic/reperfusion injury CELL00093 HK2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01427 LncAABR07025387.1 acts as a competing endogenous RNA during myocardial ischemia/reperfusion injury. Mechanistically, lncAABR07025387.1 negatively regulates miR-205 expression and subsequently upregulates ACSL4-mediated ferroptosis. . . . Down regulation Suppressor Driver Adult male Sprague Dawley rats (3 months old, 200 g) purchased from the Animal Center of Nanjing University were housed at a controlled temperature of 18-22 and humidity of 50-70% under a 12-h light/dark cycle with free access to food and water. Before the operation, the rats were fasted overnight with free access to water. At the beginning of the operation, the rats were intraperitoneally injected with chloral hydrate (0.5 ml/100 g) for sedation) and 5% additional first dose for unsatisfactory sedation and made to inhale isoflurane for anesthesia. After incising the skin, the muscle was carefully separated layer by layer, and the trachea was exposed and fixed locally with a self-made pull hook. The trachea was then cut with a 10 ml syringe needle. The anesthesia mask was then replaced with the tracheal intubation. The ventilator was connected to the anesthesia machine for isopentane inhalation (2%). The proximal left anterior descending artery (LAD) was ligated using a 6.0 Prolene suture to induce myocardial ischemia. A small semi-cylindrical plastic hose was inserted to the LAD to facilitate the opening of the knot during reperfusion and to reduce the mechanical damage to the heart tissue and blood vessels. About 5 min later, the chest cavity was temporarily closed with a non-damaging hemostatic clip. After 30 min of ischemia, the noninjury hemostatic clip was loosened, the ligation and the protective tube were removed for reperfusion, and the chest was closed. The rats in the sham group underwent the same operation without being subjected to MI/R. REF000668 ICD-11: DB98 Myocardial ischemia/reperfusion CELL00030; CELL00057 H9C2; HEK293T Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01546 miR-29a-3p, which targets IREB2, is abundant in HO-1/BMMSC-exosomes and could decrease the IREB2 protein level. The reduced IREB2 level led to an increase in the level of FTH1 and decreased the level of TFR1 through posttranscriptional regulation, which ultimately reduced the level of intracellular Fe2+ and the production of lipid ROS and inhibited the occurrence of ferroptosis in SHP-HR. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic hepatic ischemia-reperfusion injury. . . . Up regulation Suppressor Marker/Suppressor Clean-grade male Sprague-Dawley (SD) rats were purchased from China Food and Drug Administration (Beijing, China). SD rats were fed a high-fat diet (Composition: 15% triglyceride, 15% sucrose, 10% egg yolk powder, 1% cholesterol, 0.2% bile salt, 58.8% basic feed) for 20 weeks. Hematoxylin and eosin (HE) and oil red O staining showed that the area of mixed macrovesicular steatosis was more than 60% under the microscope, indicating that a model of severe steatotic liver was established successfully. A 70% liver thermal ischemia model was established, continuously blocked for 80 min, and then, the ischemic liver was obtained 24 h after reperfusion. REF000761 ICD-11: DB98 Hepatic ischemia-reperfusion injury CELL10164; CELL00459 Bone marrow mesenchymal stem cells(BMMSCs); IAR20 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01246 MiR-135b-3p was found to promote the myocardial I/R injury by downregulating GPX4 expression. The results of this study elucidate a novel function of miR-135b-3p in exacerbating cardiomyocyte ferroptosis, providing a new therapeutic target for improving myocardial ischemia/reperfusion injury. . . . Down regulation Driver Suppressor Male Sprague-Dawley rats aged 8-10 weeks and weighing 220 g were obtained from the Nanjing Biomedical Research Institute of Nanjing University. Following acclimatization for 1 week, the rats were divided into five groups of six rats each before the experiment. The establishment of the myocardial I/R model was based on previous studies . Sodium pentobarbital (45 mg/kg, i.p.) was used to anesthetize the rats, and the left coronary artery (LCA) was exposed using left thoracotomy at the fifth intercostal space. Following the LCA ligation with 7-0 silk sutures, a smooth catheter was applied to the artery to achieve ischemia for 30 min. The rats were then sacrificed 120 min after reperfusion. Rats in the sham group (without the LCA I/R) underwent surgery and were treated with saline. The miR-135b-3p group rats were injected with miR-135b-3p overexpression virus or knockdown lentivirus (1 x 108 U/ml, 0.2 ml), respectively, for five consecutive days before surgery. REF000495 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Ferroptosis (hsa04216) Cell ferroptosis
unique01510 MiR-375-3p is an important factor inducing myocardial fibrosis after Myocardial infarction, which accelerates the ferroptosis of cardiomyocytes and promotes fibrosis by down-regulating GPX4. . . . Down regulation Driver Suppressor Forty-two SD rats were randomly divided into sham operation group (n = 6) and I/R model group (n = 36). In the model group, rats were ligated with left anterior descending coronary artery to simulate MI. Specifically, after anesthetizing the animals in the I/R model group, an oblique incision was made in the third and fourth intercostal spaces of the left chest to expose the heart. Under a stereomicroscope, the junction of the pulmonary artery cone and the left atrial appendage was ligated with 6/0 noninvasive suture needle silk threads at 1-2 mm below the starting point of the coronary artery. Successful ischemia was indicated by ST segment elevation or T wave height and peaks of MI performance on electrocardiogram (ECG). The ligation was stopped after 45 minutes of ischemia, and the rats were maintained for 24 hours after reperfusion. As a drug treatment, 6 I/R model rats were treated with 20 nmol miRNA NC inhibitor (Thermo Fisher Scientific, Waltham, MA), 20 nmol miR-375-3p antagomir (Thermo Fisher Scientific, Waltham, MA) and 2 mg/kg Ferrostatin-1 (Fer-1; MCE, USA) for 28 days. The myocardial tissues of rats in the sham operation and I/R model groups as well as I/R model drug treatment group were then used for subsequent testing. REF000730 ICD-11: DB98 Cardiac fibrosis CELL10172; CELL10006 Myocardial tissue; Cardiac Fibroblasts Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00699 Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA. Suppressor . Up regulation . . Suppressor In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use. REF000919 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00816 Curcumin attenuates liver, pancreas and cardiac ferroptosis, oxidative stress and injury in ischemia/reperfusion-damaged rats by facilitating ACSL/GPx4 signaling. Suppressor . Up regulation . . Suppressor Forty female albino Wistar rats weighing 180-220 g were used in the study. Eight rats in each group were randomly assigned to five different groups: Group I (Sham); Group II (IR); Group III (IR + DMSO); Group IV (IR + Curcumin 100 mg/kg); and Group V (IR + 2 ug/kg LoxBlock-1) were determined. The animals were maintained at a temperature of 21 ± 2 and regulated humidity conditions (50 ± 5%) with a twelve-hour light/dark cycle. Throughout the experiment, the animals were fed standard commercial rat pellets and given tap water. All surgical and anesthesia procedures were performed understerile conditions. In addition, in a case of abnormal symptoms, the animals would be removed from the group and sacrificed under deep anesthesia. REF001035 ICD-11: DB98 Ischemia-Reperfusion Injury CELL10040; CELL10174; CELL10171 Liver tissues; Pancreas tissues; Heart tissues Ferroptosis (hsa04216) Cell ferroptosis
unique00452 Gossypol acetic acid significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial ischemia/reperfusion-induced ferroptotic cell death. Suppressor . Up regulation . . Suppressor A total of 55 adult male Sprague-Dawley rat (350-450 g) were anesthetized with urethane (1.5 g/kg, i.p.), then the hearts were perfused in a Langendorff system. After 30 min of stabilization, hearts were subjected to 30 min of global no-flow ischemia by stopping the perfusion. Reperfusion was followed with Krebs Henseleit (KH) buffer and GAA together for 2 h. A thermoregulated chamber kept the heart at 37 throughout the experiment. Control hearts were not subjected to I/R. The heart slices were sectioned at a thickness of 2 mm and stained with triphenyltetrazolium chloride (25 mg/100 mL) for 10 min and then fixed with 4% formaldehyde solution for 48 h to enhance color contrast. REF000593 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00409 Histochrome treatment significantly increased GPx4 and free GSH levels, but decreased Cox-2 level. HC treatment significantly decreased intracellular and mitochondrial ROS levels by upregulating the expression of Nrf2 and antioxidant genes. The substantial cardioprotective effects of HC against myocardia I/R injury by reducing ferroptosis-associated myocardial injury. Suppressor . Up regulation . . Suppressor Male Fischer 344 rats (8 weeks old and 160 to 180 g; KOATECH, Pyeongtaek-si, Korea) were anesthetized by inhalation with 2% isoflurane and intubated using an 18-gauge intravenous catheter. The rats were mechanically ventilated with medical-grade oxygen. Surgery was performed on a 37 heating pad to prevent the body from getting cold. A left thoracotomy was performed after the chest was shaved to prevent contamination during surgery. REF000557 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL10114 Cardiomyocyte Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00465 Hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) limited ferroptosis and parthanatos to alleviate oxidative stress in PC12 cells. Oxygen glucose deprivation and reperfusion injury reduced GSH/GSSG level in PC12 cells, but the reduction of GSH/GSSG ratio was regained by HSYA or AHSYB. HSYA and AHSYB activated GPX4 and system Xc- to alleviate ferroptosis. Suppressor . Up regulation . . Suppressor . REF000615 ICD-11: DB98 Ischaemia reperfusion CELL00597 PC12 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique00696 Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA. Suppressor . Up regulation . . Suppressor In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use. REF000919 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01364 Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells. . . . Up regulation Suppressor Suppressor A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery. REF000623 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00548; CELL10003 HL-1; BMSCs Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01365 Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells. . . . Down regulation Driver Suppressor A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery. REF000623 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00548; CELL10003 HL-1; BMSCs Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01366 Cellular ferroptosis is involved in the pathogenesis of Ischemia-Reperfusion Injury. BMSCs-Exo lncRNA Mir9-3hg can inhibit ferroptosis by modulating the Pum2/ PRDX6 axis to exhibit cardioprotective effectsinvivoandinvitro. Silence of PRDX6 markedly decreased cell proliferation, GSH content and Gpx4 protein level, as well as prominently increased iron ion concentration and levels of ROS content and ACSL4 protein in H/R-treated HL-1 cells. . . . Up regulation Suppressor Suppressor A total of 96 C57BL/6 male mice (20-25 g) aged 11-12 weeks were purchased from experimental animal center of experimental animal center of Guangdong Medical University. 96 mice were randomly divided into four groups (24 mice per group): Sham group (200 ul of PBS), Sham + BMSCs-Exo group (200 ul of BMSCs-Exo), I/R group (200 ul of PBS) and I/R + BMSCs-Exo group (200 ul of BMSCs-Exo). After 10 days of adaptive feeding, all mice were injected intraperitoneally with 0.4-0.5 mL/100 g 1%Pentobarbital Sodium. I/R and I/R + BMSCs-Exo group mice were subjected to cardiac I/R injury induced by ligation of the left anterior descending artery (LAD) for 30 min followed by 24 h reperfusion. Sham and Sham + BMSCs-Exo mice were sham treated and subjected to the same surgical procedures as I/R mice except that they did not receive ligation of the left anterior descending coronary artery. REF000623 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00548; CELL10003 HL-1; BMSCs Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01700 Downregulation of TNFAIP1 alleviates OGD/Rinduced neuronal damage by suppressing Nrf2/GPX4 mediated ferroptosis, which might lay the foundation for the investigation of targeted-therapy for cerebral ischemia-reperfusion injury in clinic. . . . Down regulation Driver Suppressor . REF000925 ICD-11: DB98 Cerebral ischemia/reperfusion CELL00597 PC12 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis
unique00466 Hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) limited ferroptosis and parthanatos to alleviate oxidative stress in PC12 cells. Oxygen glucose deprivation and reperfusion injury reduced GSH/GSSG level in PC12 cells, but the reduction of GSH/GSSG ratio was regained by HSYA or AHSYB. HSYA and AHSYB activated GPX4 and system Xc- to alleviate ferroptosis. Suppressor . Up regulation . . Suppressor . REF000615 ICD-11: DB98 Ischaemia reperfusion CELL00597 PC12 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique00936 Panx1 deletion induced the expression of a cytoprotective chaperone, heme oxygenase-1 (HO-1), and inhibited ferroptinophagy via the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. In summary, Panx1 deletion protects against renal ischemia/reperfusion injury (IRI) by attenuating MAPK/ERK activation in a ferroptotic pathway. . . . Down regulation Driver Suppressor C57BL/6 mice (male, 10-15 weeks old) were food-deprived for 12 h before the procedures and were anesthetized with intraperitoneal injection of 1% sodium pentobarbital solution (40 mg/kg). Using a midline abdominal incision, bilateral renal IRI was induced by clamping renal pedicles for 30 min. After removal of the clamp, the kidneys were inspected to confirm reperfusion. REF000106 ICD-11: DB98 Renal ischemia/reperfusion injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy
unique00504 As a result, irisin postconditioning may protect against lung I/R damage by suppressing ferroptosis via the Nrf2/HO-1 signaling axis. Suppressor . Up regulation . . Suppressor In vivo, the LIRI model was established as described earlier. All mice were anesthetized with pentobarbital administered intraperitoneally (50 mg/kg, Sigma-Aldrich, MO, USA). After endotracheal intubation, the mice were ventilated using a rodent ventilator (MiniVent, Harvard Apparatus, USA), with the title volume set to 7 ml/kg, the respiratory rate set to 120 times/min, and the inspiratory/expiratory ratio set to 1: 2. A noninvasive clamp was used to interrupt the left pulmonary hilum, causing lung ischemia. The clamp was released after 60 minutes of ischemia, and the left lung was reperfused for 120 minutes. Animals were euthanized via cervical dislocation at the end of the experiment. Following that, lung specimens and bronchoalveolar lavage fluid were harvested for analysis. All procedures except lung ischemia were performed on mice in the sham group. REF000685 ICD-11: DB98 Lung ischemia/reperfusion Injury CELL00557 MLE-12 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00520 MST analysis suggested that Apigenin could specifically bind to heme oxygenase 1 (HO-1) and monoamine oxidase b (MAO-B). Simultaneously, APG could attenuate ROS generation and Fe2+ accumulation, maintain mitochondria function thus inhibit ferroptosis and alleviate intestinal ischemia-reperfusion injury. Suppressor . Up regulation . . Suppressor Mice were exposed to 12/12 h of light/darkness and given free access to food and water. All C57BL/6J mice were fasted for 12 h and anesthetized by intraperitoneal injection of 1% sodium pentobarbital before modeling. Later, the superior mesenteric artery (SMA) was subjected to 45 min of global no-flow ischemia, followed by 90 min of reperfusion to induce IIRI. The successful model could be revealed by the microcirculation detector. In order to investigate the effects of APG, mice were randomly divided into different groups: Sham group, IIRI group, APG groups (2 mg/kg, 4 mg/kg and 8 mg/kg), ZnPPIX group (Protoporphyrin Zinc(), Dalian Meilun Biotech Co., Ltd., China, 10mg/kg), Selegiline group (10 mg/kg, Shandong Topscience Biotech Co., Ltd., China) and the ZnPPIX + Selegiline group (10 mg/kg ZnPPIX and 10 mg/kg Selegiline). As mentioned above, drug was intraperitoneal injected after a 10-min-ischemia. REF000709 ICD-11: DB98 Intestinal ischemia/reperfusion injury CELL10037 HUVECs Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00688 NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of dimethyl fumarate (DMF). DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic ischemia-reperfusion injury. Suppressor . Up regulation . . Suppressor The mice were randomly divided into four groups of six: sham + vehicle, sham + DMF, IR + vehicle, and IR + DMF. The mice were supplemented with DMF at a concentration of 100 mg/kg or DMSO by daily oral gavage for a week before surgery, as previously reported. As stated in a prior study, the partial warm liver IRI model was developed. Briefly, the sham group only had free hepatic portal blood vessels after laparotomy, and the blood flow was not obstructed. As for the hepatic IR group, the blood supply to the left and mid-hepatic lobes was blocked, resulting in 70% mouse liver IRI for 90 min. The mice were put on a heated blanket after surgery in order to maintain body temperature and monitor vital signs. Blood supply was restored for 6 h. Died mice were eliminated for testing prior to sample collection. The mice were euthanized after the sample were obtained. The same experimenter carried out all surgeries. REF000914 ICD-11: DB98 Hepatic ischemia-reperfusion injury CELL00541 AML12 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01545 miR-29a-3p, which targets IREB2, is abundant in HO-1/BMMSC-exosomes and could decrease the IREB2 protein level. The reduced IREB2 level led to an increase in the level of FTH1 and decreased the level of TFR1 through posttranscriptional regulation, which ultimately reduced the level of intracellular Fe2+ and the production of lipid ROS and inhibited the occurrence of ferroptosis in SHP-HR. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic hepatic ischemia-reperfusion injury. . . . Down regulation Suppressor Driver Clean-grade male Sprague-Dawley (SD) rats were purchased from China Food and Drug Administration (Beijing, China). SD rats were fed a high-fat diet (Composition: 15% triglyceride, 15% sucrose, 10% egg yolk powder, 1% cholesterol, 0.2% bile salt, 58.8% basic feed) for 20 weeks. Hematoxylin and eosin (HE) and oil red O staining showed that the area of mixed macrovesicular steatosis was more than 60% under the microscope, indicating that a model of severe steatotic liver was established successfully. A 70% liver thermal ischemia model was established, continuously blocked for 80 min, and then, the ischemic liver was obtained 24 h after reperfusion. REF000761 ICD-11: DB98 Hepatic ischemia-reperfusion injury CELL10164; CELL00459 Bone marrow mesenchymal stem cells(BMMSCs); IAR20 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00804 Both ferrostain-1 and nobiletin decreased the expression of ferroptosis-related proteins including Acyl-CoA synthetase long chain family member 4 (ACSL4) and nuclear receptor coactivator 4 (NCOA4) but not glutathione peroxidase 4 (GPX4) in rats with mature T2DM and cells with HFHG and H/R injury. Nobiletin has therapeutic potential for alleviating myocardial ischemia-reperfusion injury associated with ACSL4- and NCOA4-related ferroptosis. Suppressor . Down regulation . . Driver Male Sprague-Dawley (SD) rats (4 weeks old, 90-110 g) were obtained from the Vital River Biological company. Rats were kept in a specific-pathogen-free (SPF) environment, with access to food and tap water at an ambient temperature of 20-22 . All institutional and national guidelines for the care and use of laboratory animals were followed. The protocols were reviewed and approved by the Institution of Animal Care and Use Committee of Renmin Hospital of Wuhan University (IACUC, license no. 20200303). REF001020 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00380 Inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) could reduce ferroptosis during diabetes myocardial ischemia/reperfusion injury and the NCOA4-mediated ferritinophagy may participate in the process. Inducer . Up regulation . . Driver Fifty specific pathogen-free male SpragueDawley rats (weighing 210-240 g) were purchased from Beijing Huakang Biotechnology Co., Ltd (Beijing, China). The DS model was established by injecting 1% streptozotocin into the tail vein at 60 mg/kg dose. After 3 days, if the fasting blood glucose level was higher than 16.7 mmol/L, the DS model was successfully built. The NS and the I/R group were given 0.9% sodium chloride injection. Thereafter, the general conditions for normal and DM rats are showed in Table Table2.2. After 8 weeks, all the rats were intraperitoneally injected with 1.5% sodium pentobarbital at a dose of 0.005 mL/g. They were given electrocardiogram (ECG) monitoring management. REF000518 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00251 The administration of Cyanidin-3-glucoside (C3G) reduced the infarction area, mitigated pathological alterations, inhibited ST segment elevation, and attenuated oxidative stress and ferroptosis-related protein expression. C3G also suppressed the expressions of USP19, Beclin1, NCOA4, and LC3II/LC3I. In addition, treatment with C3G relieved oxidative stress, downregulated LC3II/LC3I, reduced autophagosome number, downregulated TfR1 expression, and upregulated the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells. Taken together, C3G could be a potential agent to protect myocardium from myocardial ischemia-reperfusion (IR) injury. Suppressor . Down regulation . . Driver Adult male Sprague Dawley (SD) rats weighing 260-280 g were purchased from Qinglongshan Animal Farm (Nanjing, China). After a week of adaptation, the rats were randomly assigned into five groups (n = 8): (1) sham group, rats receiving saline gavage and sham surgery were used as control group; (2) I/R model group, rats receiving saline gavage and left anterior descending (LAD) ligation surgery were used as the model group; (3) C3G-10 group, I/R model plus intraperitoneal injection of 10 mg/kg C3G; (4) C3G-20 group, I/R model plus intraperitoneal injection of 20 mg/kg C3G; and (5) DIL group, I/R model plus oral administration of 20 mg/kg diltiazem. C3G and DIL were dissolved in DMSO and then diluted with saline so that the DMSO concentration was less than 0.1% (v/v). REF000334 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell proliferation; Cell autophagy
unique01557 LSD1 (KDM1A) inhibition blocked ferroptosis and oxidative stress caused by renal IRI through the TLR4/NOX4 pathway, indicating that LSD1 could be a potential therapeutic target for renal ischaemia reperfusion injury (IRI). . . . Down regulation Suppressor Driver Adult male C57BL6 (C57) mice (8-12 weeks, 20-25 g) were purchased from the Animal Experiment Center of Wuhan University. All 64 mice were randomly divided into various groups by different treatments (n = 8). In sham group, after the right kidney excised, the left renal pedicles were without any treatment. In IRI group, the pedicle of the left kidney was clamped for 30 min followed by various reperfusion periods (6, 12, 24 h). To study the effects of LSD1, TCP (MedChemExpress) was injected intraperitoneally at different doses (2.5, 5, 10 mg/kg) before IRI model establishment, once a day for 1 week. TCP powder was dissolved in dimethyl sulfoxide (DMSO). In the vehicle control group, equal amount of DMSO was injected intraperitoneally. REF000767 ICD-11: DB98 Renal ischemia/reperfusion injury CELL00093 HK2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01556 LSD1 (KDM1A) inhibition blocked ferroptosis and oxidative stress caused by renal IRI through the TLR4/NOX4 pathway, indicating that LSD1 could be a potential therapeutic target for renal ischaemia reperfusion injury (IRI). . . . Up regulation Driver Driver Adult male C57BL6 (C57) mice (8-12 weeks, 20-25 g) were purchased from the Animal Experiment Center of Wuhan University. All 64 mice were randomly divided into various groups by different treatments (n = 8). In sham group, after the right kidney excised, the left renal pedicles were without any treatment. In IRI group, the pedicle of the left kidney was clamped for 30 min followed by various reperfusion periods (6, 12, 24 h). To study the effects of LSD1, TCP (MedChemExpress) was injected intraperitoneally at different doses (2.5, 5, 10 mg/kg) before IRI model establishment, once a day for 1 week. TCP powder was dissolved in dimethyl sulfoxide (DMSO). In the vehicle control group, equal amount of DMSO was injected intraperitoneally. REF000767 ICD-11: DB98 Renal ischemia/reperfusion injury CELL00093 HK2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00300 Etomidate (Eto) attenuated MIRI-induced heart failure, pathological damage, myocardial fibrosis, andinflammation, which may be related to its inhibition onferroptosis. Mechanically, the protection of Eto in myocardial ischemia reperfusion (MIR) injury (MIRI) may be achieved by activating Nrf2 pathway. Suppressor . Up regulation . . Marker/Suppressor Male Sprague-Dawley rats (8 weeks, 180 g-210 g) were provided by the experimental animal center of Beijing Institute of Life Sciences. Rats were anesthetized with 2.5% sodium pentobarbital and fixed in supine position. The LAD was ligated using a 6-0 silk for a 30 min ischemic period. Ischemia was confirmed by discoloration of heart surface and ST elevation on the electrocardiogram (ECG) recording. After 30 min, the LAD ligation was released and the reperfusion was continued for 3 h, which was confirmed by the redness of the heart surface and the decrease in ST recorded by ECG. Rats in Sham group (n = 12) underwent the same surgical procedures, except that LAD was threaded but not ligated. REF000423 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL10172 Myocardial tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00451 Gossypol acetic acid significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial ischemia/reperfusion-induced ferroptotic cell death. Suppressor . Down regulation . . Marker/Suppressor A total of 55 adult male Sprague-Dawley rat (350-450 g) were anesthetized with urethane (1.5 g/kg, i.p.), then the hearts were perfused in a Langendorff system. After 30 min of stabilization, hearts were subjected to 30 min of global no-flow ischemia by stopping the perfusion. Reperfusion was followed with Krebs Henseleit (KH) buffer and GAA together for 2 h. A thermoregulated chamber kept the heart at 37 throughout the experiment. Control hearts were not subjected to I/R. The heart slices were sectioned at a thickness of 2 mm and stained with triphenyltetrazolium chloride (25 mg/100 mL) for 10 min and then fixed with 4% formaldehyde solution for 48 h to enhance color contrast. REF000593 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00408 Histochrome treatment significantly increased GPx4 and free GSH levels, but decreased Cox-2 level. HC treatment significantly decreased intracellular and mitochondrial ROS levels by upregulating the expression of Nrf2 and antioxidant genes. The substantial cardioprotective effects of HC against myocardia I/R injury by reducing ferroptosis-associated myocardial injury. Suppressor . Up regulation . . Marker/Suppressor Male Fischer 344 rats (8 weeks old and 160 to 180 g; KOATECH, Pyeongtaek-si, Korea) were anesthetized by inhalation with 2% isoflurane and intubated using an 18-gauge intravenous catheter. The rats were mechanically ventilated with medical-grade oxygen. Surgery was performed on a 37 heating pad to prevent the body from getting cold. A left thoracotomy was performed after the chest was shaved to prevent contamination during surgery. REF000557 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL10114 Cardiomyocyte Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00413 Naringenin alleviated MI/R-induced pathological damage, inflammation and lipid peroxidation in myocardial tissue of rats. NAR adjusted the NRF2 /System xc - /GPX4 axis and improved ferroptosis. In conclusion, NAR can alleviate myocardial ischemia-reperfusion injury by regulating the Nrf2/System xc-/GPX4 axis to inhibit ferroptosis. Suppressor . Up regulation . . Marker/Suppressor 20 Sprague Dawley (SD) rats (6-8 weeks, 200-220 g) were acquired from the Second Clinical College of Guangzhou University of Traditional Chinese Medicine, and were weighed, coded, and randomly assigned to experimental groups. Rats were divided into Sham group, MI/R group, MI/R +NAR (low dose, 10 mg/kg/d) group, and MI/R +NAR (high dose, 50 mg/kg/d) group. For MI/R model, rats were anaesthetized by intraperitoneal injection of 1% pentobarbital sodium (60 mg/kg) and then received mechanical ventilation from an animal ventilator after endotracheal intubation. REF000560 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00755 Salidroside postconditioning attenuates ferroptosis-mediated lung ischemia-reperfusion injury by activating the Nrf2/SLC7A11 signaling axis. Suppressor . Up regulation . . Marker/Suppressor Following endotracheal intubation, mice were ventilated with room air at a rate of 120 cycles/min and atidal volumeof 7 mL/kg (MiniVent, Harvard Apparatus, USA). To induce ischemia, mice underwent left thoracotomy, and the left pulmonary hilum was blocked for 60 min with a microvascular clamp. After ischemia, the coronary artery was reperfused for 120 min by removing the clamp. The mice were euthanized at the end of the experiment through CO2 asphyxiation and cervical dislocation. Next, bronchoalveolar lavage fluid (BALF), blood, and lung samples were collected for testing. REF000980 ICD-11: DB98 Lung ischemia/reperfusion injury CELL00557; CELL00553 MLE-12; RAW 264.7 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00687 NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of dimethyl fumarate (DMF). DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic ischemia-reperfusion injury. Suppressor . Up regulation . . Marker/Suppressor The mice were randomly divided into four groups of six: sham + vehicle, sham + DMF, IR + vehicle, and IR + DMF. The mice were supplemented with DMF at a concentration of 100 mg/kg or DMSO by daily oral gavage for a week before surgery, as previously reported. As stated in a prior study, the partial warm liver IRI model was developed. Briefly, the sham group only had free hepatic portal blood vessels after laparotomy, and the blood flow was not obstructed. As for the hepatic IR group, the blood supply to the left and mid-hepatic lobes was blocked, resulting in 70% mouse liver IRI for 90 min. The mice were put on a heated blanket after surgery in order to maintain body temperature and monitor vital signs. Blood supply was restored for 6 h. Died mice were eliminated for testing prior to sample collection. The mice were euthanized after the sample were obtained. The same experimenter carried out all surgeries. REF000914 ICD-11: DB98 Hepatic ischemia-reperfusion injury CELL00541 AML12 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00503 As a result, irisin postconditioning may protect against lung I/R damage by suppressing ferroptosis via the Nrf2/HO-1 signaling axis. Suppressor . Up regulation . . Marker/Suppressor In vivo, the LIRI model was established as described earlier. All mice were anesthetized with pentobarbital administered intraperitoneally (50 mg/kg, Sigma-Aldrich, MO, USA). After endotracheal intubation, the mice were ventilated using a rodent ventilator (MiniVent, Harvard Apparatus, USA), with the title volume set to 7 ml/kg, the respiratory rate set to 120 times/min, and the inspiratory/expiratory ratio set to 1: 2. A noninvasive clamp was used to interrupt the left pulmonary hilum, causing lung ischemia. The clamp was released after 60 minutes of ischemia, and the left lung was reperfused for 120 minutes. Animals were euthanized via cervical dislocation at the end of the experiment. Following that, lung specimens and bronchoalveolar lavage fluid were harvested for analysis. All procedures except lung ischemia were performed on mice in the sham group. REF000685 ICD-11: DB98 Lung ischemia/reperfusion Injury CELL00557 MLE-12 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01699 Downregulation of TNFAIP1 alleviates OGD/Rinduced neuronal damage by suppressing Nrf2/GPX4 mediated ferroptosis, which might lay the foundation for the investigation of targeted-therapy for cerebral ischemia-reperfusion injury in clinic. . . . Down regulation Driver Marker/Suppressor . REF000925 ICD-11: DB98 Cerebral ischemia/reperfusion CELL00597 PC12 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis
unique00701 Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA. Suppressor . Down regulation . . Marker In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use. REF000919 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00410 Histochrome treatment significantly increased GPx4 and free GSH levels, but decreased Cox-2 level. HC treatment significantly decreased intracellular and mitochondrial ROS levels by upregulating the expression of Nrf2 and antioxidant genes. The substantial cardioprotective effects of HC against myocardia I/R injury by reducing ferroptosis-associated myocardial injury. Suppressor . Down regulation . . Marker Male Fischer 344 rats (8 weeks old and 160 to 180 g; KOATECH, Pyeongtaek-si, Korea) were anesthetized by inhalation with 2% isoflurane and intubated using an 18-gauge intravenous catheter. The rats were mechanically ventilated with medical-grade oxygen. Surgery was performed on a 37 heating pad to prevent the body from getting cold. A left thoracotomy was performed after the chest was shaved to prevent contamination during surgery. REF000557 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL10114 Cardiomyocyte Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00698 Baicalein and luteolin protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both baicalein and luteolin decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. Baicalein and luteolin reduced the ischemia/reperfusion-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA. Suppressor . Down regulation . . Marker In this study, 30 male Sprague Dawley rats (325-375 g) anesthetized using pentobarbital (1.5 g/kg, i.p.) were used for heart infarct studies,Western blot analysis, and qPCR. The isolated hearts were perfused in a Langendorff system. A water-filled latex balloon was inserted into the left ventricle cavity via mitral valve and linked to a physiological pressure transducer (AD Instruments, MLT884) for continuous monitoring of left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP). Left ventricular developed pressure (LVDP) was calculated as the difference between LVSP and LVEDP (LVDP = LVSP-LVEDP). Measurements were recorded using PowerLab system and Chart 8 software (ADInstrument, Bella Vista, New South Wales, Australia). The hearts were stable for 30 min, and then subjected to 45 min of global ischemia by halting perfusion, followed by 1 h of reperfusion with Krebs-Henseleit (KH) bicarbonate buffer gassed with 95% O2, 5% CO2 at 37 (pH 7.4). The infarcted myocardium was measured using triphenyltetrazolium chloride(TTC, 25 mg/mL) staining. The KH buffer containing 118 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25 mM NaHCO 31.3 mM CaCl2, and 11 mM glucose was filtered through a 0.22 uM pore before use. REF000919 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01499 MiR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft ischemia reperfusion injury. And HUCB-MSCs-exos inhibited the expression of DMT1 by delivering miR-23a-3p, which suppressed cardiomyocyte ferroptosis after myocardial infarction. . . . Up regulation Driver Driver . REF000722 ICD-11: DB98 Ischemia-Reperfusion Injury CELL10164; CELL00459 Bone marrow mesenchymal stem cells(BMMSCs); IAR20 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01498 MiR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft ischemia reperfusion injury. And HUCB-MSCs-exos inhibited the expression of DMT1 by delivering miR-23a-3p, which suppressed cardiomyocyte ferroptosis after myocardial infarction. . . . Down regulation Suppressor Driver . REF000722 ICD-11: DB98 Ischemia-Reperfusion Injury CELL10164; CELL00459 Bone marrow mesenchymal stem cells(BMMSCs); IAR20 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01665 SEMA5A-IT1 overexpression upregulated the expression of BCL2 and SLC7A11 through sponging miR-143-3p, thereby protecting cardiomyocytes against apoptotic and ferroptosis cell death. In conclusion, we propose that SEMA5A-IT1, which is transported to cardiomyocytes through circulating sEVs, is an important regulatory molecule that protects cardiomyocytes from ischemia-reperfusion injury. . . . Up regulation Suppressor Suppressor . REF000871 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00286 AC16 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00754 Salidroside postconditioning attenuates ferroptosis-mediated lung ischemia-reperfusion injury by activating the Nrf2/SLC7A11 signaling axis. Suppressor . Up regulation . . Suppressor Following endotracheal intubation, mice were ventilated with room air at a rate of 120 cycles/min and atidal volumeof 7 mL/kg (MiniVent, Harvard Apparatus, USA). To induce ischemia, mice underwent left thoracotomy, and the left pulmonary hilum was blocked for 60 min with a microvascular clamp. After ischemia, the coronary artery was reperfused for 120 min by removing the clamp. The mice were euthanized at the end of the experiment through CO2 asphyxiation and cervical dislocation. Next, bronchoalveolar lavage fluid (BALF), blood, and lung samples were collected for testing. REF000980 ICD-11: DB98 Lung ischemia/reperfusion injury CELL00557; CELL00553 MLE-12; RAW 264.7 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00689 NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of dimethyl fumarate (DMF). DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic ischemia-reperfusion injury. Suppressor . Up regulation . . Suppressor The mice were randomly divided into four groups of six: sham + vehicle, sham + DMF, IR + vehicle, and IR + DMF. The mice were supplemented with DMF at a concentration of 100 mg/kg or DMSO by daily oral gavage for a week before surgery, as previously reported. As stated in a prior study, the partial warm liver IRI model was developed. Briefly, the sham group only had free hepatic portal blood vessels after laparotomy, and the blood flow was not obstructed. As for the hepatic IR group, the blood supply to the left and mid-hepatic lobes was blocked, resulting in 70% mouse liver IRI for 90 min. The mice were put on a heated blanket after surgery in order to maintain body temperature and monitor vital signs. Blood supply was restored for 6 h. Died mice were eliminated for testing prior to sample collection. The mice were euthanized after the sample were obtained. The same experimenter carried out all surgeries. REF000914 ICD-11: DB98 Hepatic ischemia-reperfusion injury CELL00541 AML12 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01666 SEMA5A-IT1 overexpression upregulated the expression of BCL2 and SLC7A11 through sponging miR-143-3p, thereby protecting cardiomyocytes against apoptotic and ferroptosis cell death. In conclusion, we propose that SEMA5A-IT1, which is transported to cardiomyocytes through circulating sEVs, is an important regulatory molecule that protects cardiomyocytes from ischemia-reperfusion injury. . . . Down regulation Driver Suppressor . REF000871 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00286 AC16 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01688 The results of dual luciferase reporter gene technique indicated SLC7A11 as the target gene of miR-27a. In the current study, miR-27a upregulates ferroptosis to aggravate cerebral ischemia-reperfusion injury by SLC7A11. . . . Down regulation Driver Suppressor The rats were anesthetized by intraperitoneal injection of pentobarbital sodium (40 mg/kg). Before the experiment, the rats were fasted for 8-10 h and ensured sufficient water. The left common carotid artery (CCA) and left external carotid artery (ECA) were ligated after skin incision in the middle of the neck. In the common carotid artery cut a small incision. In order to induce ischemia, a cord plug was inserted through the incision into the internal carotid artery (ICA) and then to the origin of the middle cerebral artery (MCA). After ischemia for 2 h, the rats were anesthetized and gently pulled out the cord plug. At the end of the reperfusion time, the rats were euthanized by injection of a minimal lethal dose of anesthesia. REF000907 ICD-11: DB98 Cerebral ischemia/reperfusion CELL10005 Brain tissues Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01547 miR-29a-3p, which targets IREB2, is abundant in HO-1/BMMSC-exosomes and could decrease the IREB2 protein level. The reduced IREB2 level led to an increase in the level of FTH1 and decreased the level of TFR1 through posttranscriptional regulation, which ultimately reduced the level of intracellular Fe2+ and the production of lipid ROS and inhibited the occurrence of ferroptosis in SHP-HR. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic hepatic ischemia-reperfusion injury. . . . Down regulation Suppressor Marker/Suppressor/Driver Clean-grade male Sprague-Dawley (SD) rats were purchased from China Food and Drug Administration (Beijing, China). SD rats were fed a high-fat diet (Composition: 15% triglyceride, 15% sucrose, 10% egg yolk powder, 1% cholesterol, 0.2% bile salt, 58.8% basic feed) for 20 weeks. Hematoxylin and eosin (HE) and oil red O staining showed that the area of mixed macrovesicular steatosis was more than 60% under the microscope, indicating that a model of severe steatotic liver was established successfully. A 70% liver thermal ischemia model was established, continuously blocked for 80 min, and then, the ischemic liver was obtained 24 h after reperfusion. REF000761 ICD-11: DB98 Hepatic ischemia-reperfusion injury CELL10164; CELL00459 Bone marrow mesenchymal stem cells(BMMSCs); IAR20 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01044 A novel pathway of USP7/p53/TfR1 has been identified in the ischemia/reperfusion (I/R)-treated rat hearts, where up-regulation of USP7 promotes ferrptosis via activation of the p53/TfR1 pathway. . . . Up regulation Driver Marker/Suppressor/Driver Male Sprague-Dawley (SD) rats (250-300 g) were purchased from the Laboratory Animal Center, Xiangya School of Medicine, Central South University, China. Briefly, a left thoracotomy was carried out in the fourth intercostal space and the heart was exposed via opening the pericardium. The left coronary artery was around via a 4-0 silk suture and a snare was formed by passing both ends of the suture via a short polyethylene tubing. Blockage of the coronary artery was conducted via clamping the snare against the heart surface. Reperfusion was performed by release of the snare. The sham group conducted the same procedure but without ischemia (the snare was not tightened). To establish the I/R injury model, the rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion. REF000260 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
dupunique01044 A novel pathway of USP7/ p53/TfR1 has been identified in the ischemia/reperfusion (I/R)-treated rat hearts, where up-regulation of USP7 promotes ferrptosis via activation of the p53/TfR1 pathway. . . . Up regulation Driver Marker/Suppressor/Driver Male Sprague-Dawley (SD) rats (250-300 g) were purchased from the Laboratory Animal Center, Xiangya School of Medicine, Central South University, China. Briefly, a left thoracotomy was carried out in the fourth intercostal space and the heart was exposed via opening the pericardium. The left coronary artery was around via a 4-0 silk suture and a snare was formed by passing both ends of the suture via a short polyethylene tubing. Blockage of the coronary artery was conducted via clamping the snare against the heart surface. Reperfusion was performed by release of the snare. The sham group conducted the same procedure but without ischemia (the snare was not tightened). To establish the I/R injury model, the rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion. REF000260 ICD-11: DB98 Ischemia-Reperfusion Injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00252 The administration of Cyanidin-3-glucoside (C3G) reduced the infarction area, mitigated pathological alterations, inhibited ST segment elevation, and attenuated oxidative stress and ferroptosis-related protein expression. C3G also suppressed the expressions of USP19, Beclin1, NCOA4, and LC3II/LC3I. In addition, treatment with C3G relieved oxidative stress, downregulated LC3II/LC3I, reduced autophagosome number, downregulated TfR1 expression, and upregulated the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells. Taken together, C3G could be a potential agent to protect myocardium from myocardial ischemia-reperfusion (IR) injury. Suppressor . Down regulation . . Marker/Suppressor/Driver Adult male Sprague Dawley (SD) rats weighing 260-280 g were purchased from Qinglongshan Animal Farm (Nanjing, China). After a week of adaptation, the rats were randomly assigned into five groups (n = 8): (1) sham group, rats receiving saline gavage and sham surgery were used as control group; (2) I/R model group, rats receiving saline gavage and left anterior descending (LAD) ligation surgery were used as the model group; (3) C3G-10 group, I/R model plus intraperitoneal injection of 10 mg/kg C3G; (4) C3G-20 group, I/R model plus intraperitoneal injection of 20 mg/kg C3G; and (5) DIL group, I/R model plus oral administration of 20 mg/kg diltiazem. C3G and DIL were dissolved in DMSO and then diluted with saline so that the DMSO concentration was less than 0.1% (v/v). REF000334 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell proliferation; Cell autophagy
unique01434 Lidocaine could regulate inflammation, oxidative stress and ferroptosis by blocking the p38 MAPK signaling pathway. Thus, lidocaine could act as a novel therapeutic treatment of patients with Lung Ischemia-reperfusion (I/R) injury. Suppressor Down regulation . . Driver . . REF000676 ICD-11: DB98 Lung ischemia/reperfusion Injury CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00519 MST analysis suggested that Apigenin could specifically bind to heme oxygenase 1 (HO-1) and monoamine oxidase b (MAO-B). Simultaneously, APG could attenuate ROS generation and Fe2+ accumulation, maintain mitochondria function thus inhibit ferroptosis and alleviate intestinal ischemia-reperfusion injury. Suppressor Up regulation . . Suppressor . Mice were exposed to 12/12 h of light/darkness and given free access to food and water. All C57BL/6J mice were fasted for 12 h and anesthetized by intraperitoneal injection of 1% sodium pentobarbital before modeling. Later, the superior mesenteric artery (SMA) was subjected to 45 min of global no-flow ischemia, followed by 90 min of reperfusion to induce IIRI. The successful model could be revealed by the microcirculation detector. In order to investigate the effects of APG, mice were randomly divided into different groups: Sham group, IIRI group, APG groups (2 mg/kg, 4 mg/kg and 8 mg/kg), ZnPPIX group (Protoporphyrin Zinc(), Dalian Meilun Biotech Co., Ltd., China, 10mg/kg), Selegiline group (10 mg/kg, Shandong Topscience Biotech Co., Ltd., China) and the ZnPPIX + Selegiline group (10 mg/kg ZnPPIX and 10 mg/kg Selegiline). As mentioned above, drug was intraperitoneal injected after a 10-min-ischemia. REF000709 ICD-11: DB98 Intestinal ischemia/reperfusion injury CELL10037 HUVECs Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00376 Trypsin-mediated sensitization of pancreatic acinar cells to ferroptosis may be targeted for the prevention and treatment of pancreatitis in mice. Conversely, olanzapine administration protected against pancreatic ferroptotic damage and experimental pancreatitis in Gpx4-deficient mice. Inducer . Down regulation . . Suppressor For cerulein-induced acute pancreatitis, male mice (age, 8-10 wk) received 7 hourly intraperitoneal injections of 50 g/kg cerulein in sterile saline. Olanzapine was repeatedly administered orally by gavage at a dose of 5 mg/kg to mice at 3 and 12 hours after the first cerulein injection, while controls were treated by oral administration with vehicle (smooth peanut butter).The parameters of acute pancreatitis were assessed 12 hours after the last cerulein treatment. For the induction of chronic pancreatitis, male mice (age, 8-10 wk) were fed a LieberDeCarli ethanol (5% vol/vol) liquid diet for 4 weeks (F1258; Bio-Serv, Flemington,NJ).In parallel, olanzapine was administered orally by gavage at a dose of 5 mg/kg to mice (3 times per week, over 4 weeks), while controls were treated by oral administration with vehicle. The parameters of chronic pancreatitis were assessed in mice 4 weeks after feeding them the LieberDeCarli ethanol liquid diet. REF000510 ICD-11: DC31 Pancreatitis CELL00571 266-6 (CRL-2151) Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00329 Wedelolactone promoted the transcriptional activity and the selenium sensitivity of GPX4. Moreover, the protective effects of Wed in caerulein-stimulated pancreatic acinar cells were markedly abrogated by the down-regulation of GPX4. Wed mitigated Acute pancreatitis (AP) and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis. Suppressor . Up regulation . . Suppressor The 8-weeks old male Sprague-Dawley rats (bodyweight 250-300 g) were purchased from Liaoning changsheng biotechnology co. LTD (Benxi, China). The rats in the taurocholate-induced acute pancreatitis group (Taur, n = 6) were fasted overnight, after anesthesia the hepatic portal of the bile duct was clamped and 3.5% sodium taurocholate (Aladdin, Shanghai, China) in a volume of 1 ml/kg were retrogradely injected into the biliopancreatic duct at a constant speed (0.1 ml/min). The rats in the Sham group (n = 6) were received the laparotomy and the same volume of saline solution. The rats in the disulfiram treatment group (Taur + Disul, n = 6) were administrated with 100 mg/kg pyroptosis antagonist disulfiram (Aladdin) by intraperitoneal (i.p.) injection before the surgery. The rats in the ferrostatin-1 treatment group (Taur + Fer-1, n = 6) were i.p. administered 2.5 mol/kg ferroptosis antagonist ferrostatin-1 (Aladdin) 1 h before the surgery. REF000451 ICD-11: DC31 Acute pancreatitis CELL00600 AR42J Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212); Necroptosis (hsa04217) Cell ferroptosis; Cell pyroptosis
unique00377 Trypsin-mediated sensitization of pancreatic acinar cells to ferroptosis may be targeted for the prevention and treatment of pancreatitis in mice. Conversely, olanzapine administration protected against pancreatic ferroptotic damage and experimental pancreatitis in Gpx4-deficient mice. Suppressor . Up regulation . . Suppressor For cerulein-induced acute pancreatitis, male mice (age, 8-10 wk) received 7 hourly intraperitoneal injections of 50 g/kg cerulein in sterile saline. Olanzapine was repeatedly administered orally by gavage at a dose of 5 mg/kg to mice at 3 and 12 hours after the first cerulein injection, while controls were treated by oral administration with vehicle (smooth peanut butter).The parameters of acute pancreatitis were assessed 12 hours after the last cerulein treatment. For the induction of chronic pancreatitis, male mice (age, 8-10 wk) were fed a LieberDeCarli ethanol (5% vol/vol) liquid diet for 4 weeks (F1258; Bio-Serv, Flemington,NJ).In parallel, olanzapine was administered orally by gavage at a dose of 5 mg/kg to mice (3 times per week, over 4 weeks), while controls were treated by oral administration with vehicle. The parameters of chronic pancreatitis were assessed in mice 4 weeks after feeding them the LieberDeCarli ethanol liquid diet. REF000510 ICD-11: DC31 Pancreatitis CELL00571 266-6 (CRL-2151) Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00536 Taken together, the present study, to the best of our knowledge, is the first to reveal a protective role for Ginsenoside Rg3 in mice with acute pancreatitis by suppressing oxidative stressrelated ferroptosis and the activation of the NRF2/HO1 pathway. Suppressor . Up regulation . . Suppressor Male C57BL/6 mice (8 weeks old; SPF; weighing 24-26 g, n = 16 in total) were purchased from SPF (Beijing) Biotechnology Co., Ltd. All mice were housed in an environmentally controlled room at a temperature ranging from 20 to 24 on a 12 h light/dark cycle and used in the experiments following an overnight fast with water, availablead libitum. All procedures followed the Principles of Laboratory Animal Care (NIH publication number 85Y23, revised in 1996), and the experimental protocol was approved by the Animal Care Committee, Nanjing Medical University (NMU-2021JK-085). REF000741 ICD-11: DC31 Acute pancreatitis CELL00600 AR42J Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00535 Taken together, the present study, to the best of our knowledge, is the first to reveal a protective role for Ginsenoside Rg3 in mice with acute pancreatitis by suppressing oxidative stressrelated ferroptosis and the activation of the NRF2/HO1 pathway. Suppressor . Up regulation . . Marker/Suppressor Male C57BL/6 mice (8 weeks old; SPF; weighing 24-26 g, n = 16 in total) were purchased from SPF (Beijing) Biotechnology Co., Ltd. All mice were housed in an environmentally controlled room at a temperature ranging from 20 to 24 on a 12 h light/dark cycle and used in the experiments following an overnight fast with water, availablead libitum. All procedures followed the Principles of Laboratory Animal Care (NIH publication number 85Y23, revised in 1996), and the experimental protocol was approved by the Animal Care Committee, Nanjing Medical University (NMU-2021JK-085). REF000741 ICD-11: DC31 Acute pancreatitis CELL00600 AR42J Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01096 Furin protects epithelial cells from DSS-induced ferroptosis-like cell injury and alleviates experimental ulcerative colitis by activating the Nrf2-Gpx4 signaling pathway. . . . Up regulation Suppressor Suppressor Male C57BL/6 mice wild-type (WT), 8 weeks of age, were from Chongqing Medical University, China. Mice were divided into four groups (n = 10-13 per group), control group, MPTP group, h-Trx-1 Tg group, and h-Trx-1 Tg + MPTP group. Control and h-Trx-1 Tg groups were administered saline only. For the Trx-1 knockdown experiment, mice were divided into six groups (n = 10-13 per group), control + saline group, control + MPTP group, AAV9-vehicle + saline group, AAV9-vehicle + MPTP group, AAV9-shRNA-mTrx-1 + saline group, and AAV9-shRNA-mTrx-1 + MPTP. REF000337 ICD-11: DD71 Ulcerative colitis CELL00118 NCM460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00167 Curculigoside (CUR) could increase the selenium sensitivity and promote GPX4 transcription level in IEC-6 cells. Knockdown of GPX4 significantly blocked the protective effects of CUR on cell death, GSH and MDA contents as well as LDH activity in ferroptotic IEC-6 cells. Taken together, CUR protects against ferroptosis in ulcerative colitis (UC) by the induction of GPX4, which presents a potential agent for UC treatment. Suppressor . Up regulation . . Suppressor Male C57BL/6J mice (8 weeks) were housed in a controlled condition at 25 , 45-55% humidity and 12 h light/dark cycle. All mice were randomly divided into five groups: Vehicle group, mice received dextran sulfate sodium (DSS group), DSS mice received ferrostatin-1 (DSS + Fer-1 group), DSS mice received low dose of CUR (DSS + CUR-L group), and DSS mice received high dose of CUR (DSS + CUR-H group). In the experiments, 3% DSS (D122347, Aladdin, Shanghai, China) in drinking water for 7 days was prepared to induce UC models. Mice in DSS + Fer-1 group were intraperitoneally injected with 5 mg/kg Fer-1 (S7243, Selleck, Shanghai, China) every two days from the day before DSS induction. In addition, mice in DSS + CUR-L or DSS + CUR-H group received intragastric administration with CUR (HY-N0705, Med Chem Express, Shanghai, China) at 50 mg/kg or 100 mg/kg once a day for 7 days during DSS administration. REF000222 ICD-11: DD71 Ulcerative colitis CELL00595 IEC-6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique01095 Furin protects epithelial cells from DSS-induced ferroptosis-like cell injury and alleviates experimental ulcerative colitis by activating the Nrf2-Gpx4 signaling pathway. . . . Up regulation Suppressor Marker/Suppressor Male C57BL/6 mice wild-type (WT), 8 weeks of age, were from Chongqing Medical University, China. Mice were divided into four groups (n = 10-13 per group), control group, MPTP group, h-Trx-1 Tg group, and h-Trx-1 Tg + MPTP group. Control and h-Trx-1 Tg groups were administered saline only. For the Trx-1 knockdown experiment, mice were divided into six groups (n = 10-13 per group), control + saline group, control + MPTP group, AAV9-vehicle + saline group, AAV9-vehicle + MPTP group, AAV9-shRNA-mTrx-1 + saline group, and AAV9-shRNA-mTrx-1 + MPTP. REF000337 ICD-11: DD71 Ulcerative colitis CELL00118 NCM460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00440 Ferroptosis was shown to be involved in 5-FU-induced intestinal mucositis, and Tertiary butylhydroquinone markedly hampered its activation. Mechanistically, TBHQ activated Nrf2 effectively and selective Nrf2 knockdown significantly reduced the anti-ferroptotic functions of TBHQ in 5-FU-treated HIECs. Suppressor . Up regulation . . Marker/Suppressor Male C57/BL6 mice (eight weeks old, 18-20 g) were purchased from Chengdu Dossy Experimental Animals (China). All the mice were housed in plastic cages with free access to food and water at 25 with a 12 h light/dark cycle. The mice were randomly divided into four groups (n = 6 mice/group): the control group, 5-FU group, 5-FU + TBHQ group, and 5-FU + Fer-1 group. 50 mg/kg body weight 5-FU was intraperitoneally (i.p.) injected into the mice of the 5-FU, 5-FU + TBHQ and 5-FU + Fer-1 group per day for five days to induce intestinal mucositis. Starting on the same day, the mice in the 5-FU + TBHQ and 5-FU + Fer-1 group were treated with TBHQ (10 mg/kg body weight; in DMSO, i.p. injection) or Fer-1 (2.5 mol/kg body weight; in DMSO; i.p. injection) once daily for eight days (days 18). Starting on the same day, the mice of the 5-FU group were treated with equivalent volumes of dimethyl sulfoxide (DMSO) for eight days. REF000586 ICD-11: DD71 Intestinal mucositis CELL00307 HIEC Ferroptosis (hsa04216) Cell ferroptosis
unique00375 The therapeutic effects of Astragalus polysaccharide on DSS-induced Ulcerative colitis by blocking ferroptosis in IECs. Furthermore, our results revealed that APS-mediated inhibition of ferroptosis was associated with the NRF2/HO-1 pathway. Suppressor . Down regulation . . Marker/Suppressor Six-eight-week-old male C57BL/6 mice weighing 19.74 ± 0.77 g were purchased from Shanghai Laboratory. To investigate the therapeutic effect of APS on DSS-induced colitis, mice were randomly divided into the following 5 groups (n = 5 each): control, DSS, DSS + APS (100 mg/kg), DSS + APS (200 mg/kg), and DSS + APS (300 mg/kg). The mice in the DSS + APS (100 mg/kg), DSS + APS (200 mg/kg), and DSS + APS (300 mg/kg) groups were intraperitoneally injected with 100, 200, and 300 mg/kg APS once a day, respectively from day 3 to day 10. REF000509 ICD-11: DD71 Ulcerative colitis CELL00046 Caco-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01669 IRF7 upregulated SLC11A2 transcription by inhibiting miR-375-3p expression, thereby prompting ferroptosis of colonic ECs and ulcerative colitis progression in DSS-treated mice. . . . Up regulation Driver Driver Mice were orally administered 0.1 g/kg Co-Q10 daily for 8 weeks after the DMM model was established to investigate the therapeutic effect of Co-Q10 in GPX4-CKO mice with osteoarthritis. Mice and rats were anaesthetized with pentobarbital. Destabilization of the medial meniscus (DMM) surgery was performed under a microscope. The incision was sutured and disinfected daily until it healed. REF000880 ICD-11: DD71 Ulcerative colitis CELL10009 Colonic tissue Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01670 IRF7 upregulated SLC11A2 transcription by inhibiting miR-375-3p expression, thereby prompting ferroptosis of colonic ECs and ulcerative colitis progression in DSS-treated mice. . . . Down regulation Suppressor Driver Mice were orally administered 0.1 g/kg Co-Q10 daily for 8 weeks after the DMM model was established to investigate the therapeutic effect of Co-Q10 in GPX4-CKO mice with osteoarthritis. Mice and rats were anaesthetized with pentobarbital. Destabilization of the medial meniscus (DMM) surgery was performed under a microscope. The incision was sutured and disinfected daily until it healed. REF000880 ICD-11: DD71 Ulcerative colitis CELL10009 Colonic tissue Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00708 B-Caryophyllene (BCP) activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. These results revealed that macrophage ferroptosis is a potential therapeutic target for ulcerative colitis and identified a novel mechanism of BCP in ameliorating experimental colitis. Suppressor Up regulation . . Suppressor . After 10 days of acclimation, the mice were randomly assigned to five groups (n = 6 each): control, model (3% DSS), BCP (50 mg/kg body weight), AM630 (10 mg/kg body weight) and AM630 + BCP. All mice (except those in the control group) were provided with a solution of filtered water containing 3% (w/v) DSS ad libitum during the experiment period. The mice in the control group received only normal drinking water. For the treatment groups, BCP was dissolved in corn oil at doses of 50 mg/kg and administered orally once a day. The mice in the AM630 group were injected intraperitoneally with AM630 (10 mg/kg). The mice in the AM630 + BCP group received an intraperitoneal injection of AM630 (10 mg/kg) given 30 min before the BCP (50 mg/kg). During the study, symptomatic parameters including body weight, stool character and bleeding were recorded daily. The disease activity index (DAI) was calculated according to our previous study. After 8 days of treatment, all mice were anesthetized with pentobarbital sodium. The blood and colon samples were collected for subsequent analysis. The collected blood was left to coagulate for 20 min at room temperature and centrifuged for 15 min at 3000 g to obtain the serum. REF000924 ICD-11: DD71 Ulcerative colitis CELL00553 RAW 264.7 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00307 OTSSP167 (a MELK-selective inhibitor) treatment obviously inhibited ferroptosis in the intestinal tissue and suppressed macrophage infiltration and M1 polarization, which reduced the secretion of pro-inflammatory factors. OTSSP167 inhibited AKT/IKK/P65 and ERK/IKK/P65 signaling cascades both in vivo and in vitro, which may help alleviate Inflammatory bowel disease. Suppressor Down regulation . . Driver . Male C57BL/6 wild-type mice (6-8 weeks) were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. (Shanghai, China). The mice were randomly divided into 3 groups: the control group, colitis group andtreatmentgroup (n = 8 mice per group). The control group was provided drinking water without DSS, while the colitis group and the treatment group were provided drinking water containing 2.5% DSS. Mice in the treatment group received anintragastric administrationof 2 mg/kg OTSSP167 every other day. The condition of the mice was monitored daily by performing a general examination and assessing changes in body weight. Starting on the fifth day, the colitis group and the treatment group were switched to drinking water without DSS. REF000434 ICD-11: DD7Z Inflammatory bowel disease CELL00553 RAW264.7 Fatty acid metabolism (hsa01212); PI3K-Akt signaling pathway (hsa04151); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00291 Baicalein up-regulated GPX4 and reduced TFR1 level in melanocytes treated with RSL3+FAC. Baicalein protected melanocytes against ferroptosis through up-regulating GPX4. Ferroptosis might be pervasive in the occurrence and development of vitiligo, and could be proposed as the potential therapeutic target. Suppressor . Up regulation . . Suppressor . REF000412 ICD-11: ED63 Vitiligo CELL10082 HEM-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00292 Baicalein up-regulated GPX4 and reduced TFR1 level in melanocytes treated with RSL3+FAC. Baicalein protected melanocytes against ferroptosis through up-regulating GPX4. Ferroptosis might be pervasive in the occurrence and development of vitiligo, and could be proposed as the potential therapeutic target. Suppressor . Down regulation . . Marker/Suppressor/Driver . REF000412 ICD-11: ED63 Vitiligo CELL10082 HEM-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00656 Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis. Suppressor . Up regulation . . Suppressor Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies. REF000887 ICD-11: FA01 Knee osteoarthritis CELL10008 Chondrocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00655 Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis. Suppressor . Up regulation . . Marker/Suppressor Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies. REF000887 ICD-11: FA01 Knee osteoarthritis CELL10008 Chondrocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00658 Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis. Suppressor . Up regulation . . Suppressor Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies. REF000887 ICD-11: FA01 Knee osteoarthritis CELL10008 Chondrocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00657 Biochanin A (BCA) could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for knee osteoarthritis. Suppressor . Down regulation . . Driver Male mice were purchased from Guangzhou University of Chinese Medicine's Experimental Animal Center C57BL/6 mice (7-week-old, 20 g) (Guangzhou, China). After one week of adaptively feeding with chow meals and sterilized water, the animals were separated into five groups of ten mice randomly assigned to the negative control (NC); model, positive control (PC); model group; high dosage of BCA treatment (BCA-H) group; and low dosage of BCA treatment (BCA-L) group. The iron overload mice model was designed based on earlier research. Except for the NC group, mice were administered ID intraperitoneally (500 mg/kg) once a week for eight weeks. In the right knee joints, OA was induced with the initial injection of iron dextran two weeks after the injection by destabilizing the medial meniscus (DMM) using a microscope. After the operation, the positive control group was administered with NAC intragastrically (100 mg/kg) for eight weeks. BCA-H and BCA-L groups were administered 20 mg/kg and 40 mg/kg of BCA separately for eight weeks according to previous studies. REF000887 ICD-11: FA01 Knee osteoarthritis CELL10008 Chondrocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00442 Stigmasterol (STM) attenuates chondrocyte injury induced by IL-1 by regulating ferroptosis via down-regulation of SREBF2, which suggests that STM may have potential as a novel therapeutic method for knee osteoarthritis. Suppressor Down regulation . . Driver . . REF000589 ICD-11: FA01 Knee osteoarthritis CELL00572 ATDC5 Ferroptosis (hsa04216) Cell ferroptosis
unique01668 In mouse osteoarthritis model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. . . . Down regulation Driver Suppressor Mice were orally administered 0.1 g/kg Co-Q10 daily for 8 weeks after the DMM model was established to investigate the therapeutic effect of Co-Q10 in GPX4-CKO mice with osteoarthritis. Mice and rats were anaesthetized with pentobarbital. Destabilization of the medial meniscus (DMM) surgery was performed under a microscope. The incision was sutured and disinfected daily until it healed. REF000877 ICD-11: FA05 Osteoarthritis CELL10008 Chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01817 Inhibition of SCP2 markedly protects mitochondria and reduces LPO levels, attenuating chondrocyte ferroptosis in vitro and alleviating the progression of osteoarthritis (OA) in rats. In OA cartilage, the positive cells for SCP2 and iron level were markedly elevated while the expression of GPX4 (a major anti-peroxidant enzyme) was markedly decreased. . . . Down regulation Driver Marker/Suppressor A total of 16 Sprague-Dawley rats (6 weeks old, female) were purchased from Guangdong Medical Laboratory Animal Center (Foshan, China) and randomly divided into four groups (n = 4): Sham, Hulth, Hulth + ScpI2 (0.1 mg/kg) (Vitas-M, Apeldoorn, Netherlands), Hulth + ScpI2 (0.5 mg/kg). One week after surgery, the rats were intraarticularly injected with vehicle or ScpI2 twice a week for 4 consecutive weeks. REF001047 ICD-11: FA05 Osteoarthritis CELL10008 Chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01459 The RNA-binding protein SND1 promotes the degradation of GPX4 by destabilizing the HSPA5 mRNA and suppressing HSPA5 expression, promoting ferroptosis in osteoarthritis chondrocytes. . . . Down regulation Driver Suppressor A rat model of OA with destabilization of the medial meniscus was established . After anesthetization with 3% pentobarbital sodium (Tocris, Avonmouth, UK), the hair on the right knee was clipped. Right knee was subsequently exposed before an incision was made in the medial aspect of the joint capsule, then the anterior cruciate ligament was transected, and the medial meniscus was completely resected in a manner that did not injure the articular cartilage. Subsequently, the joint was irrigated with normal saline, the capsule was sutured with 4-0 chromic catgut, and the skin was closed with 4-0 nylon mattress sutures. And the rats were allowed to move, eat, and drink freely after surgery. Experimental groups are as follows: sham group (A medial incision was made to expose the knee joint cavity, and sutured), OA model group (Destabilization of the medial meniscus), sh-NC group (OA rats were injected with sh-NC), and sh-SND1 group (OA rats were injected with sh-SND1). REF000692 ICD-11: FA05 Osteoarthritis CELL10008 Chondrocytes Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01460 The RNA-binding protein SND1 promotes the degradation of GPX4 by destabilizing the HSPA5 mRNA and suppressing HSPA5 expression, promoting ferroptosis in osteoarthritis chondrocytes. . . . Up regulation Suppressor Suppressor A rat model of OA with destabilization of the medial meniscus was established . After anesthetization with 3% pentobarbital sodium (Tocris, Avonmouth, UK), the hair on the right knee was clipped. Right knee was subsequently exposed before an incision was made in the medial aspect of the joint capsule, then the anterior cruciate ligament was transected, and the medial meniscus was completely resected in a manner that did not injure the articular cartilage. Subsequently, the joint was irrigated with normal saline, the capsule was sutured with 4-0 chromic catgut, and the skin was closed with 4-0 nylon mattress sutures. And the rats were allowed to move, eat, and drink freely after surgery. Experimental groups are as follows: sham group (A medial incision was made to expose the knee joint cavity, and sutured), OA model group (Destabilization of the medial meniscus), sh-NC group (OA rats were injected with sh-NC), and sh-SND1 group (OA rats were injected with sh-SND1). REF000692 ICD-11: FA05 Osteoarthritis CELL10008 Chondrocytes Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00916 NCOA4 was upregulated in a JNK- JUN signaling-dependent manner in which JUN could directly bind to the promoter of Ncoa4 and initial the transcription of Ncoa4. This work highlights the role of JNK- JUN-NCOA4 axis and ferritinophagy in chondrocyte ferroptosis and osteoarthritis (OA) pathogenesis, suggesting this axis as a potential target for OA treatment. . . . Up regulation Driver Driver Adult male C57BL/6 mice (eight weeks of age) were used for in vivo experiments. We randomly divided mice into four groups with 9 mice per group: SHAM + AAV9-GFP, SHAM + AAV9-NCOA4, DMM + AAV9-GFP, and DMM + AAV9-NCOA4 groups. For in vivo experiment of SP600125 administration, we randomly divided mice into three groups with 6 mice per group: DMM + AAV9-GFP, DMM + AAV9-GFP + SP600125, and DMM + AAV9-NCOA4 + SP600125. 10 ul of SP600125 (1 mg/kg) or vehicle solution was injected articularly once per week for 7 weeks. REF000979 ICD-11: FA05 Osteoarthritis CELL10008 Chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00227 Both IL-1 and FAC induced ferroptosis related protein expression changes in chondrocytes.In this study, we use Interleukin-1 Beta (IL-1) to simulate inflammation and ferric ammonium citrate (FAC) to simulate the iron overload in vitro. Furthermore, inhibition of ferroptosis, by intraarticular injection of ferrostatin-1, in our case, seems to be a novel and promising option for the prevention of osteoarthritis. Inducer Up regulation . . Driver . Thirty-two 8 weeks old male C57BL/6 mice were used in this study. Eight mice were randomly allocated to the sham surgery group. After anesthetized by intraperitoneal injection of pentobarbital (35 mg/kg), sham surgery group were subjected to sham surgery. Then, destabilized medial meniscus (DMM) were performed to establish the OA model in twenty-four mice. DMM mice were randomly divided into three groups (N=8 for each group): the DMM group, the DMM+0.1mg/kg ferrostain-1 group and the DMM+1mg/kg ferrostain-1 group. The DMM+0.1 mg/kg ferrostain-1 group and the DMM+1mg/kg ferrostain-1 group were intraarticularly injected with 0.1 mg/kg or 1 mg/kg ferrostain-1 respectively. The sham surgery group and DMM group were intraarticularly injected with same volume of vehicle. The injection was repeated twice a week for 8 consecutive weeks. REF000294 ICD-11: FA05 Osteoarthritis CELL10008 chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00228 Both IL-1 and FAC induced ferroptosis related protein expression changes in chondrocytes.In this study, we use Interleukin-1 Beta (IL-1) to simulate inflammation and ferric ammonium citrate (FAC) to simulate the iron overload in vitro. Furthermore, inhibition of ferroptosis, by intraarticular injection of ferrostatin-1, in our case, seems to be a novel and promising option for the prevention of osteoarthritis. Suppressor Down regulation . . Driver . Thirty-two 8 weeks old male C57BL/6 mice were used in this study. Eight mice were randomly allocated to the sham surgery group. After anesthetized by intraperitoneal injection of pentobarbital (35 mg/kg), sham surgery group were subjected to sham surgery. Then, destabilized medial meniscus (DMM) were performed to establish the OA model in twenty-four mice. DMM mice were randomly divided into three groups (N=8 for each group): the DMM group, the DMM+0.1mg/kg ferrostain-1 group and the DMM+1mg/kg ferrostain-1 group. The DMM+0.1 mg/kg ferrostain-1 group and the DMM+1mg/kg ferrostain-1 group were intraarticularly injected with 0.1 mg/kg or 1 mg/kg ferrostain-1 respectively. The sham surgery group and DMM group were intraarticularly injected with same volume of vehicle. The injection was repeated twice a week for 8 consecutive weeks. REF000294 ICD-11: FA05 Osteoarthritis CELL10008 chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00172 Homocysteine (Hcy) is an amino acid involved in gene methylation. Hcy upregulates oxidative stress and ferroptosis in the nucleus pulposus via enhancing GPX4 methylation, and is a new contributing factor in intervertebral disc degeneration (IVDD). Inducer . Down regulation . . Suppressor Thirty male C57BL/6 mice (8 weeks old, average weight 25 g) were divided into three groups. Blank group: Ten mice were fed with normal diet and water. HHcy group: Ten mice were fed with a high Met diet (normal diet with 2% l-methionine). HHcy + Folic Acidrescue group: Ten mice were fed withhigh Met diet (normal diet with 2% l-methionine), and injected with Folic Acid (1.0 umol/kg/d) twice a week two months later. At the beginning of treatment, mice were anesthetized with anintraperitoneal injectionof 0.3% (w/v)pentobarbital sodium(20 uL/g) before surgery and disc degeneration was induced by stabbing the C5-6 and C6-7 discs with a 32G needle. REF000228 ICD-11: FA80 Intervertebral disc degeneration CELL10090 Nucleus pulposus cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necrosis
unique01046 Inflammatory cytokine IL-6 appeared in Intervertebral disc degeneration (IDD) aggravates its degeneration by inducing cartilage cell ferroptosis. This is caused partially by inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway. The ferroptosis-inhibitory effect exhibited by overexpressing miR-10a-5p was achieved by promoting GPX4 and ferroportin-1 (FPN1) but suppressing divalent metal transporter 1 (DMT1) expression in IL-6-treated cartilage cells. . . . Up regulation Suppressor Suppressor . REF000262 ICD-11: FA80 Intervertebral disc degeneration CELL10008 Chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01779 Hesperidin may protect HNP cells from degeneration by suppressing ferroptosis in an oxidative stress-dependent via enhancing the expression of Nrf2 and suppressing the NF-B pathway. The evidence will provide a possible basis for future targeted treatment for intervertebral disc degeneration. Suppressor . Up regulation . . Marker/Suppressor Male C57BL/6 mice (10-12 weeks) were devoted to generate needle puncture-induced intervertebral disc degeneration model. For intervertebral disc degeneration (IVDD) treatment, hesperidin was administratedorally and the dose was calculated in reference to previous studies using themetrological conversion formula between human and mouse. The dosein mice is = 5.5 mg/kg x 70 kg x 0.0026/20g = 9.1 x 5.5 mg/kg = 50.05 mg/kg ~50 mg/kg. REF001008 ICD-11: FA80 Intervertebral disc degeneration CELL10090 human nucleus pulposus(NP) cells Fatty acid metabolism (hsa01212); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique01564 BMSC-EV-loaded circ_0072464 inhibited NPC ferroptosis to relieve intervertebral disc degeneration (IDD) via upregulation of miR-431-mediated NRF2, therefore providing a potential therapeutic target against IDD. . . . Up regulation Suppressor Marker/Suppressor . REF000775 ICD-11: FA80 Intervertebral disc degeneration CELL10001; CELL10003 Bone marrow tissues; BMSCs Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01565 BMSC-EV-loaded circ_0072464 inhibited NPC ferroptosis to relieve intervertebral disc degeneration (IDD) via upregulation of miR-431-mediated NRF2, therefore providing a potential therapeutic target against IDD. . . . Down regulation Driver Marker/Suppressor . REF000775 ICD-11: FA80 Intervertebral disc degeneration CELL10001; CELL10003 Bone marrow tissues; BMSCs Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01048 Inflammatory cytokine IL-6 appeared in Intervertebral disc degeneration (IDD) aggravates its degeneration by inducing cartilage cell ferroptosis. This is caused partially by inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway. The ferroptosis-inhibitory effect exhibited by overexpressing miR-10a-5p was achieved by promoting GPX4 and ferroportin-1 (FPN1) but suppressing divalent metal transporter 1 (DMT1) expression in IL-6-treated cartilage cells. . . . Down regulation Suppressor Driver . REF000262 ICD-11: FA80 Intervertebral disc degeneration CELL10008 Chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01047 Inflammatory cytokine IL-6 appeared in Intervertebral disc degeneration (IDD) aggravates its degeneration by inducing cartilage cell ferroptosis. This is caused partially by inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway. The ferroptosis-inhibitory effect exhibited by overexpressing miR-10a-5p was achieved by promoting GPX4 and ferroportin-1 (FPN1) but suppressing divalent metal transporter 1 (DMT1) expression in IL-6-treated cartilage cells. . . . Up regulation Suppressor Marker/Suppressor . REF000262 ICD-11: FA80 Intervertebral disc degeneration CELL10008 Chondrocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01830 Circ-STC2 and TFR2 expressions were up-regulated in intervertebral disc degeneration (IDD) tissues, and miR-486-3p expression was down-regulated. Circ-STC2 inhibits the cell viability, induced the ferroptosis of the TBHP treated NPCs via targeting miR-486-3p/TFR2 axis. . . . Up regulation Driver Driver . REF001053 ICD-11: FA80 Intervertebral disc degeneration CELL10090 Nucleus pulposus cells (NPCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01831 Circ-STC2 and TFR2 expressions were up-regulated in intervertebral disc degeneration (IDD) tissues, and miR-486-3p expression was down-regulated. Circ-STC2 inhibits the cell viability, induced the ferroptosis of the TBHP treated NPCs via targeting miR-486-3p/TFR2 axis. . . . Down regulation Suppressor Driver . REF001053 ICD-11: FA80 Intervertebral disc degeneration CELL10090 Nucleus pulposus cells (NPCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01780 The current study proved for the first time that Hesperidin may protect HNP cells from degeneration by suppressing ferroptosis in an oxidative stress-dependent via enhancing the expression of Nrf2 and suppressing the NF-kB pathway. The evidence will provide a possible basis for future targeted treatment for intervertebral disc degeneration. Suppressor Down regulation . . Driver . Male C57BL/6 mice (10-12 weeks) were devoted to generate needle puncture-induced intervertebral disc degeneration model. For intervertebral disc degeneration (IVDD) treatment, hesperidin was administratedorally and the dose was calculated in reference to previous studies using themetrological conversion formula between human and mouse. The dosein mice is = 5.5 mg/kg x 70 kg x 0.0026/20g = 9.1 x 5.5 mg/kg = 50.05 mg/kg ~50 mg/kg. REF001008 ICD-11: FA80 Intervertebral disc degeneration CELL10090 human nucleus pulposus(NP) cells Fatty acid metabolism (hsa01212); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique00483 FBXO9 was downregulated in Zoledronic acid-treated osteoclast and promoted osteoclasts ferroptosis by inhibiting FBXO9 -mediated p53 ubiquitination and degradation. The study provided a possible theoretical target for the clinical treatment of Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ). Inducer Down regulation . . Suppressor . . REF000642 ICD-11: FB81 Bisphosphonates-related osteonecrosis of jaw CELL00553 RAW264.7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
dupunique00483 FBXO9 was downregulated in Zoledronic acid-treated osteoclast and promoted osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation. The study provided a possible theoretical target for the clinical treatment of Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ). Inducer Up regulation . . Driver . . REF000642 ICD-11: FB81 Bisphosphonates-related osteonecrosis of jaw CELL00553 RAW264.7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00225 High glucose induces ferroptosis via increased ROS/lipid peroxidation/glutathione depletion in type 2 diabetic osteoporosis. More importantly, melatonin significantly reduced the level of ferroptosis and improved the osteogenic capacity of MC3T3-E1 through activating the Nrf2/HO-1 pathway in vivo and in vitro. Suppressor . Up regulation . . Marker/Suppressor Eight-week-old specific-pathogen-free Sprague Dawley rats weighing 220 ± 20 g were purchased from China Medical University, Department of Experimental Animals. A total of 60 rats were used to determine the targets of bone histomorphometry; 45 rats were used to establish a diabetic model, and remaining 15 rats were divided into a control group. The diabetic rats were divided into three groups (n = 15 each) treated with intraperitoneal injection of high-dose melatonin (50 mg/kg, HMT group), intraperitoneal injection of low-dose melatonin (10 mg/kg, LMT group), and a control T2DM group. REF000287 ICD-11: FB83 Type 2 diabetic osteoporosis CELL00550 MC3T3-E1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01416 ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of Endometriosis. . . . Up regulation Suppressor Suppressor Female BALB/c mice (4-6 weeks old, 18-20 g) were obtained from Shanghai Regan Biotechnology Co., Ltd. (Shanghai, China) and were reared in a specific, pathogen-free facility. After 1 week of acclimatization, mice were randomly divided into two groups: the donor group (n = 10) and recipient groups (n = 10). Ovariosteresis and estradiol valerate injection (0.5 ug/mouse/week; Aladdin, Shanghai, China) was carried out to avoid differences in the estrous cycle. Mice were anesthetized by 2% isoflurane, and then the ovaries on both sides were exposed through flank incisions and removed. Donor mice were sacrificed under isoflurane anesthesia, and each uterine horn of the donor mice was concentrated and peeled in warm PBS to remove uterine muscle. Endometrial tissues were weighed and cut into small fragments with scissors and resuspended in sterile PBS with 1 x ampicillin (Beyotime, Shanghai, China). After that, endometrium preparation was intraperitoneally injected into two recipient mice (50 mg/mouse). Two weeks after EM transplantation, endometriosis lesions and eutopic endometrial tissues were removed from the peritoneal cavities and uteri. REF000664 ICD-11: GA10 Endometriosis CELL10061; CELL10120; CELL10117 Eutopic endometrial tissues; normal ESCs (NESCs); ectopic ESCs (EESCs) Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique00705 Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of endometriosis by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Suppressor . Up regulation . . Suppressor . REF000922 ICD-11: GA10 Endometriosis CELL00038; CELL10109 THP1; Macrophages Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01417 ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of Endometriosis. . . . Down regulation Driver Suppressor Female BALB/c mice (4-6 weeks old, 18-20 g) were obtained from Shanghai Regan Biotechnology Co., Ltd. (Shanghai, China) and were reared in a specific, pathogen-free facility. After 1 week of acclimatization, mice were randomly divided into two groups: the donor group (n = 10) and recipient groups (n = 10). Ovariosteresis and estradiol valerate injection (0.5 ug/mouse/week; Aladdin, Shanghai, China) was carried out to avoid differences in the estrous cycle. Mice were anesthetized by 2% isoflurane, and then the ovaries on both sides were exposed through flank incisions and removed. Donor mice were sacrificed under isoflurane anesthesia, and each uterine horn of the donor mice was concentrated and peeled in warm PBS to remove uterine muscle. Endometrial tissues were weighed and cut into small fragments with scissors and resuspended in sterile PBS with 1 x ampicillin (Beyotime, Shanghai, China). After that, endometrium preparation was intraperitoneally injected into two recipient mice (50 mg/mouse). Two weeks after EM transplantation, endometriosis lesions and eutopic endometrial tissues were removed from the peritoneal cavities and uteri. REF000664 ICD-11: GA10 Endometriosis CELL10061; CELL10120; CELL10117 Eutopic endometrial tissues; normal ESCs (NESCs); ectopic ESCs (EESCs) Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique01642 Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression. . . . Up regulation Driver Driver Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each. REF000851 ICD-11: GA30 Primary ovarian insufficiency CELL00263; CELL00057 ES-2; HEK 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique01644 Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression. . . . Down regulation Suppressor Driver Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each. REF000851 ICD-11: GA30 Primary ovarian insufficiency CELL00263; CELL00057 ES-2; HEK 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique01640 Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression. . . . Down regulation Suppressor Driver Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each. REF000851 ICD-11: GA30 Primary ovarian insufficiency CELL00263; CELL00057 ES-2; HEK 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique01641 Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression. . . . Up regulation Driver Marker/Suppressor/Driver Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each. REF000851 ICD-11: GA30 Primary ovarian insufficiency CELL00263; CELL00057 ES-2; HEK 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique01643 Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression. . . . Down regulation Suppressor Marker/Suppressor/Driver Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each. REF000851 ICD-11: GA30 Primary ovarian insufficiency CELL00263; CELL00057 ES-2; HEK 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique01639 Pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced primary ovarian insufficiency (POI). BNC1 directly regulates Nf2 expression. BNC1 deficiency downregulates NF2 expression, which reduces YAP phosphorylation and promote YAP nuclear accumulation. YAP activation upregulates Tfrc and Acsl4 expression. . . . Down regulation Suppressor Marker/Suppressor/Driver Ovaries collected from 12-week-old mice were fixed in 2.5% glutaraldehyde at room temperature for 2 h and then at 4 overnight. The ovaries were washed with PBS three times for 10 min. Then, the ovaries were fixed with 1% osmic acid for 1 h and washed with PBS three times for 10 min each. The ovaries were fixed with 2% uranyl acetate for 30 min; dehydrated with 50%, 70%, 90% and 100% ethanol for 10 min each; and washed with 100% acetone twice for 15 min each. REF000851 ICD-11: GA30 Primary ovarian insufficiency CELL00263; CELL00057 ES-2; HEK 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique00119 Busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility. Inducer . Down regulation . . Suppressor Eight-week-old healthy ICR male mice, weighted 20-24 g, were provided by Experimental Animal Center of Nantong University (Nantong, China). For the first animal study, eight-week-old ICR male mice were randomly assigned to four groups: control, busulfan, busulfan plus Fer-1 and busulfan plus DFO groups (n = 6 per group). Mice were anesthetized and then given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight. The solution containing busulfan was directly injected from the scrotum into testicular transverse diameter. Fer-1 and DFO were administered by intraperitoneal injectionat concentrations of 1 mg/kg and 30 mg/kg respectively three times a week after busulfan injection. Four weeks later, the epididymal spermatozoa and testes from all mice were collected for assessment. REF000174 ICD-11: GB04 Male infertility CELL10158 Testicular tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00120 Busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility. Inducer . Down regulation . . Marker/Suppressor Eight-week-old healthy ICR male mice, weighted 20-24 g, were provided by Experimental Animal Center of Nantong University (Nantong, China). For the first animal study, eight-week-old ICR male mice were randomly assigned to four groups: control, busulfan, busulfan plus Fer-1 and busulfan plus DFO groups (n = 6 per group). Mice were anesthetized and then given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight. The solution containing busulfan was directly injected from the scrotum into testicular transverse diameter. Fer-1 and DFO were administered by intraperitoneal injectionat concentrations of 1 mg/kg and 30 mg/kg respectively three times a week after busulfan injection. Four weeks later, the epididymal spermatozoa and testes from all mice were collected for assessment. REF000174 ICD-11: GB04 Male infertility CELL10158 Testicular tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00118 Busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility. Inducer . Down regulation . . Marker/Suppressor Eight-week-old healthy ICR male mice, weighted 20-24 g, were provided by Experimental Animal Center of Nantong University (Nantong, China). For the first animal study, eight-week-old ICR male mice were randomly assigned to four groups: control, busulfan, busulfan plus Fer-1 and busulfan plus DFO groups (n = 6 per group). Mice were anesthetized and then given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight. The solution containing busulfan was directly injected from the scrotum into testicular transverse diameter. Fer-1 and DFO were administered by intraperitoneal injectionat concentrations of 1 mg/kg and 30 mg/kg respectively three times a week after busulfan injection. Four weeks later, the epididymal spermatozoa and testes from all mice were collected for assessment. REF000174 ICD-11: GB04 Male infertility CELL10158 Testicular tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00247 Long-term administration of medicine-containing Aristolactam I (ALI) was reported to be related to aristolochic acid nephropathy (AAN), which was attributed to ALI-induced nephrotoxicity. ALI dose-dependently inhibited these protein contents of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4), which could be partly rescued by Tin-protoporphyrin IX (SnPP) and mitoTEMPO co-treatment. Inducer . Down regulation . . Marker/Suppressor . REF000323 ICD-11: GB55 Aristolochic acid nephropathy CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00547 Renal expression of ACSL4 was markedly enhanced by IRI and reduced by vitamin K1. Vitamin K1 as a potent inhibitor of ferroptosis, and hence, it represents a potential drug for the treatment of pathological cell death processes during acute kidney injury in humans. Suppressor . Down regulation . . Driver All mice used in our in vivo studies were 8-week-old males of the C57BL/6J background. Kidneys were exposed via a midline abdominal incision and bilateral renal pedicle clamping for 35 min using microaneurysm clamps (Aesculap Inc., Center Valley, PA, USA). Throughout the surgical procedure, the mice were kept under isoflurane narcosis, and their body temperature was maintained at 36-37 by continuous monitoring using a temperature-controlled, self-regulated heating system (Fine Science Tools, Heidelberg, Germany). After clamps were removed, kidney reperfusion was confirmed visually before the abdomen was closed in two layers using standard 6-0 sutures. To maintain fluid balance, all mice were supplemented with 1 ml of prewarmed PBS administered intraperitoneally directly after surgery. After 48 h of reperfusion, the mice were sacrificed, blood samples were obtained by retrobulbar puncture, and kidneys were collected for analysis. REF000765 ICD-11: GB60 Acute kidney injury CELL00554; CELL00095; CELL10162 NIH3T3; HT-1080; MCTs Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01474 GPX4 was predicted as a target of miR-214-3p. Moreover, inhibiting miR-214-3p enhanced the expressions of GPX4 and SLC7A11 while decreasing the ACSL4 expression. Furthermore, miR-214-3p down-regulation protected against TEC death and renal tubule damage both in vitro and in vivo. According to these findings, inhibiting miR-214-3p would alleviate TEC ferroptosis in acute kidney injury (AKI) induced by cisplatin (cis-AKI) via GPX4. . . . Down regulation Driver Suppressor The C57BL/6 male mice (8-week-old, weighing approximately 20-25 g) were procured from Beijing Huafukang Bioscience Co. Inc. The mice were raised under the SPF condition. Cisplatin was injected into the mice intraperitoneally and only once at a dose of 30 mg/kg to induce AKI, while the control mice were injected with PBS. Intravenous administration of 10 mg/kg of agomir negative control (agomir NC) or agomir miR-214-3p (GenePharma Co. Ltd, Shanghai, China) was performed for the control group mice and model group mice, respectively. The ferroptosis inhibitor named Fer-1 (#S7243, Selleck Chemicals, Houston, TX, USA) was dissolved in DMSO and then diluted in 0.9% NaCl to prepare separate Fer-1 solutions each with a concentration of 0.2 mg/mL. Fer-1 was injected into the mice intraperitoneally, 1 h prior to injecting cisplatin, while the control mice received the injection of only 0.9% NaCl in 0.1% DMSO. Both experimental and control group mice were sacrificed at Day 1, 2, and 3, separately, post-cisplatin injection. REF000704 ICD-11: GB60 Acute kidney injury CELL00556 TCMK-1 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00489 In vitro and in vivo experiments indicated the prominent nephroprotective effects of polydatin against ferroptosis in cisplatin-induced acute kidney injury models, occurred at least partly through inhibiting excessive intracellular free iron accumulation and ROS production, rescuing GSH consumption, and enhancing GPx4 activity, thereby decreasing lipid peroxidation and ferroptosis sensitivity and ultimately attenuating the pathological progression of AKI. Suppressor . Up regulation . . Suppressor Male C57BL/6 mice (8-10 weeks of age, weight 20-25 g) were purchased from Experimental Animal Center of the Fourth Military Medical University (Xi'an, China) and bred in an experimental animal room of SPF grade. They were randomly divided into four groups: control (equivalent saline containing 1% DMSO) group (n = 5), cisplatin (20 mg/kg dissolved in saline) only group (n = 7), cisplatin + polydatin (40 mg/kg dissolved in 1% DMSO) group (n = 7), and cisplatin+ Fer-1 (5 mg/kg dissolved in 1% DMSO) group (n = 7) were administered intraperitoneally. Mice were injected with cisplatin once; PD or Fer-1 was given 1 h before and 24 h after cisplatin. Animals were ethically sacrificed by dislocating their spines at 48 h after cisplatin injection, and whole blood and kidneys were collected for further analysis. REF000653 ICD-11: GB60 Acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01034 Rev-erb-a (NR1D1) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-a limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice. . . . Down regulation Driver Driver/Suppressor Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury. REF000249 ICD-11: GB60 Acute kidney injury CELL10152; CELL10151; CELL10149 MRTEpiC; mRTECs; M4100-57 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01032 Rev-erb-b (NR1D2) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-b limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice. . . . Down regulation Driver Driver/Suppressor Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury. REF000249 ICD-11: GB60 Acute kidney injury CELL10152; CELL10151; CELL10149 MRTEpiC; mRTECs; M4100-57 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00707 Dioscin exerts a reno-protective effect by decreasing renal oxidative injury, apoptosis and ferroptosis through the Nrf2/HO-1 signaling pathway, providing a new insight into acute kidney injury prevention. Suppressor . Up regulation . . Suppressor Six-week-old male Wistar rats (170-200 g) were obtained from Changsheng Biotechnology Co., Ltd. (Changchun, China), and all of them were fed under SPF-conditions. The rats were acclimatized to natural light/dark cycles at a controlled temperature of 22 + 2 with free access to food and water. The experiment was comprised of four groups: the C group (0.5% carboxymethyl cellulose sodium [CMC-Na], n = 6); the Dio group (dioscin-treated rats, n = 6); the CP group (cisplatin-treated mice, n = 6); and the Dio + CP group (dioscin plus cisplatin-treated rats, n = 6). Rats were gavaged with dioscin (60 mg/kg) for ten days, and cisplatin (10 mg/kg) was intraperitoneally injected once on the seventh day. REF000923 ICD-11: GB60 Acute kidney injury CELL00093 HK2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique00438 Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. Suppressor . Down regulation . . Driver Male C57BL/6 mice (aged 6-8 weeks and weighing 22-25g) were obtained from the Experimental Animal Center, Sichuan Provincial Peoples Hospital, and were fed a standard laboratory diet. LPS and ISL were dissolved in normal saline and 0.5% Tween-20/saline, respectively. AKI mice were developed by intraperitoneal (i.p.) LPS injection. A total of 30 mice were randomly divided into six groups (n = 5): control, ISL, Fer, LPS, LPS plus ISL, and LPS plus Fer. An intraperitoneal injection of LPS (10 mg/kg) was made to induce septic AKI. ISL was administered via gavage at 50 mg/kg 30 min before LPS injection. Mice were dosed intraperitoneally with Fer (Ferrostatin-1, SML0583, Sigma-Aldrich, St. Louis, MO) at 5 mg/kg. Mice were sacrificed by cervical dislocation 8 h after LPS injection. Kidney tissue and serum samples were collected concurrently. REF000585 ICD-11: GB60 Acute kidney injury CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01301 ADAMTS13 alleviated CP-induced inflammatory response and oxidative stress in acute kidney injury mice, during which the Nrf2 signaling pathway was abnormal. Overall, ADAMTS-13-regulated Nrf2 signaling inhibits ferroptosis to ameliorate CP-induced AKI. . . . Up regulation Suppressor Marker/Suppressor C57BL/6 mice (8-12 week) mice purchased from Cavens (Changzhou, China) were divided into four groups: control (saline), CDDP only (CP, 20 mg/kg; MCE, United States), CP (20 mg/kg) + ADAMTS13 (0.1 nmol/kg) and CP (20 mg/kg) + ADAMTS13 (0.3 nmol/kg). Each group contained 5 mice. 0.1 and 0.3 nmol/kg rhADAMTS13 were injected into the caudal vein daily for 3 days after surgery. REF000551 ICD-11: GB60 Acute kidney injury CELL10129 Kidney tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00706 Dioscin exerts a reno-protective effect by decreasing renal oxidative injury, apoptosis and ferroptosis through the Nrf2/HO-1 signaling pathway, providing a new insight into acute kidney injury prevention. Suppressor . Up regulation . . Marker/Suppressor Six-week-old male Wistar rats (170-200 g) were obtained from Changsheng Biotechnology Co., Ltd. (Changchun, China), and all of them were fed under SPF-conditions. The rats were acclimatized to natural light/dark cycles at a controlled temperature of 22 + 2 with free access to food and water. The experiment was comprised of four groups: the C group (0.5% carboxymethyl cellulose sodium [CMC-Na], n = 6); the Dio group (dioscin-treated rats, n = 6); the CP group (cisplatin-treated mice, n = 6); and the Dio + CP group (dioscin plus cisplatin-treated rats, n = 6). Rats were gavaged with dioscin (60 mg/kg) for ten days, and cisplatin (10 mg/kg) was intraperitoneally injected once on the seventh day. REF000923 ICD-11: GB60 Acute kidney injury CELL00093 HK2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique00206 Pachymic acid has a protective effect on ischemiareperfusion induced acute kidney injury in mice, which may be associated with the inhibition of ferroptosis in the kidneys through direct or indirect activation of NRF2, and upregulation of the expression of the downstream ferroptosis related proteins, GPX4, SLC7A11 and HO1. Suppressor . Up regulation . . Marker/Suppressor A total of 30 C57BL/6 male mice (8-10 weeks; 20-25 g body weight) were purchased from Chongqing Medical University (Chongqing, China). The mice were anesthetized with 50-60 mg/kg of pentobarbital sodium (cat. no. P3761; Sigma-Aldrich; Merck KGaA) by intraperitoneal injection; the skin at the surgical area was wiped with 70% alcohol. The incision was positioned at the left and right sides of the spine (0.5 cm), and the incision length was 1-1.5 cm along the back. The kidneys were subsequently pulled out from the incision to expose the renal pedicle. A microaneurysm clip was used to clamp the pedicle to block the blood flow to the kidney and induce renal ischemia. Complete ischemia was indicated by a change in the color of the kidney from red to dark purple within a few seconds. After 40 min of ischemia, the microaneurysm clips were released to allow each kidney to start reperfusion, which was indicated by the change of the kidney color to red. REF000269 ICD-11: GB60 Acute kidney injury CELL10129 Kidney tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01033 Rev-erb-a (NR1D1) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-a limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice. . . . Down regulation Driver Suppressor Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury. REF000249 ICD-11: GB60 Acute kidney injury CELL10152; CELL10151; CELL10149 MRTEpiC; mRTECs; M4100-57 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01031 Rev-erb-b (NR1D2) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-b limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice. . . . Down regulation Driver Suppressor Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury. REF000249 ICD-11: GB60 Acute kidney injury CELL10152; CELL10151; CELL10149 MRTEpiC; mRTECs; M4100-57 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01326 Downregulation of Cx43 ( GJA1) can inhibit ferroptosis by restoring the level of SLC7A11 in the system xctransporter and alleviate cisplatin-induced acute kidney injury. And downregulating Cx43 not only inhibits ferroptosis, but also inhibits apoptosis. . . . Down regulation Driver Suppressor Thirty-two male C57BL/6 mice (20 ± 2) g (Beijing Weitonglihua Experimental Animal Technology Co., Ltd.) were bred in individually ventilated cages (IVC) at SPF conditions. After one-week acclimation mice were divided randomly into four groups: control group, cisplatin group (20 mg/kg cisplatin dissolved in saline), cisplatin + Fer-1 group (5 mg/kg Fer-1 dissolved in DMSO), and cisplatin + gap27 group (35 ug/kg gap27 dissolved in DMSO). There were eight animals in each group and 20 mg/kg cisplatin was given to each animal once by intraperitoneal injection except mice in the control group. Fer-1 and gap27 was administered 1 h before the injection of cisplatin. REF000583 ICD-11: GB60 Acute kidney injury CELL00093 HK2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00245 Histological kidney injury, proximal tubule damages, and renal cell death, such as apoptosis and ferroptosis, were reduced by loganin treatment. Also, pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-, reduced by loganin treatment. Furthermore, loganin deactivated the extracellular signal-regulated kinases (ERK) 1 and 2 during acute kidney injury. Suppressor Down regulation . . Driver . All experiments were performed according to the protocols approved by the Animal Care Committee of Wonkwang University. AKI was induced by a single intraperitoneal injection of cisplatin (10 mg/kg). One h before cisplatin injection, mice in the loganin group received 1, 10, or 20 mg/kg of loganin orally, and mice in the U0126 group received 10 mg/kg of U0126 intraperitoneally. They were sacrificed at 72 h after cisplatin injection, and their blood and kidneys were collected. REF000320 ICD-11: GB60 Acute kidney injury CELL10129 Kidney tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00703 Aspirin can upregulate SLC7A11 and GPX4 expression by suppressing COX2. Our results demonstrated that ferroptosis in renal tubular cells contributes to Diabetic kidney disease (DKD) development and that diabetes-related ferroptosis was inhibited through the downregulation of COX2 by aspirin, thus retarding the progression of DKD. Suppressor . Up regulation . . Suppressor These mice were on eight weeks old male DBA/2J background (n = 36, HFK Bioscience, Beijing, China). They were randomized one of the six groups: control normal mice group (NC); diabetic mice group (DM); diabetic mice group (Fer-1), who intraperitoneal injected Fer-1 (Selleck, Houston, TX, USA); diabetic mice group (vehicle-P), who intraperitoneal injected 1% dimethyl sulfoxide (DMSO); diabetic mice group (As), who intragastric administrated Aspirin (Solarbio, Beijing, China); diabetic mice group (vehicle-G), who intragastric administrated 0.5% sodium carboxymethyl cellulose (Na-CMC; Solarbio, Beijing, China). Diabetes models were induced with 5 consecutive days of a single intraperitoneal injection of streptozotocin 40 mg/kg (dissolved in 0.1 M citrate buffer, pH 4.5; SigmaAldrich, St Louis, MO, USA). Control mice only was injected the same volume of citrate buffer. In the Fer-1 or vehicle-P groups, the diabetic mice were treated respectively with Fer-1 (2.5 umol/kg, dissolved in 1% DMSO) or 1% DMSO during the duration of treatment for 12-week every day. And in the AS and vehicle-G groups, the diabetic mice were treated respectively with aspirin (50 mg/kg, dissolved in 0.5% Na-CMC) or 0.5% Na-CMC for 12-week every day. REF000920 ICD-11: GB61.Z Diabetic kidney disease CELL00093 HK-2 Ferroptosis (hsa04216) Cell ferroptosis
unique00498 Ferroptosis in HK-2 cells was induced by HG and was suppressed by Platycodin D (PD). GPX4 expression was downregulated in HG-induced cells and was upregulated by PD. Thus, PD suppressed ferroptosis of HK-2 cells by upregulating GPX4 expression, suggesting that PD might be an effective drug for Diabetic nephropathy therapy. Suppressor . Up regulation . . Suppressor . REF000671 ICD-11: GB61 Diabetic nephropathy CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01207 Interaction of salusin- ( TOR2A) with ferroptosis formed a positive feedback, thereby contributing to HG-induced HK-2 cell injury and diabetic nephropathy. Mechanistically, salusin inactivated nuclear factor erythroidderived 2like 2 (Nrf2) signaling, thus contributing to HGinduced ferroptosisrelated changes in HK2 cells. . . . Down regulation Driver Marker/Suppressor . REF000461 ICD-11: GB61 Diabetic nephropathy CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00702 Aspirin can upregulate SLC7A11 and GPX4 expression by suppressing COX2. Our results demonstrated that ferroptosis in renal tubular cells contributes to Diabetic kidney disease (DKD) development and that diabetes-related ferroptosis was inhibited through the downregulation of COX2 by aspirin, thus retarding the progression of DKD. Suppressor . Down regulation . . Marker These mice were on eight weeks old male DBA/2J background (n = 36, HFK Bioscience, Beijing, China). They were randomized one of the six groups: control normal mice group (NC); diabetic mice group (DM); diabetic mice group (Fer-1), who intraperitoneal injected Fer-1 (Selleck, Houston, TX, USA); diabetic mice group (vehicle-P), who intraperitoneal injected 1% dimethyl sulfoxide (DMSO); diabetic mice group (As), who intragastric administrated Aspirin (Solarbio, Beijing, China); diabetic mice group (vehicle-G), who intragastric administrated 0.5% sodium carboxymethyl cellulose (Na-CMC; Solarbio, Beijing, China). Diabetes models were induced with 5 consecutive days of a single intraperitoneal injection of streptozotocin 40 mg/kg (dissolved in 0.1 M citrate buffer, pH 4.5; SigmaAldrich, St Louis, MO, USA). Control mice only was injected the same volume of citrate buffer. In the Fer-1 or vehicle-P groups, the diabetic mice were treated respectively with Fer-1 (2.5 umol/kg, dissolved in 1% DMSO) or 1% DMSO during the duration of treatment for 12-week every day. And in the AS and vehicle-G groups, the diabetic mice were treated respectively with aspirin (50 mg/kg, dissolved in 0.5% Na-CMC) or 0.5% Na-CMC for 12-week every day. REF000920 ICD-11: GB61.Z Diabetic kidney disease CELL00093 HK-2 Ferroptosis (hsa04216) Cell ferroptosis
unique01153 Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice. . . . Up regulation Suppressor Suppressor Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established. REF000389 ICD-11: GB61 Diabetic nephropathy CELL00564 MPC5 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00704 Aspirin can upregulate SLC7A11 and GPX4 expression by suppressing COX2. Our results demonstrated that ferroptosis in renal tubular cells contributes to Diabetic kidney disease (DKD) development and that diabetes-related ferroptosis was inhibited through the downregulation of COX2 by aspirin, thus retarding the progression of DKD. Suppressor . Up regulation . . Suppressor These mice were on eight weeks old male DBA/2J background (n = 36, HFK Bioscience, Beijing, China). They were randomized one of the six groups: control normal mice group (NC); diabetic mice group (DM); diabetic mice group (Fer-1), who intraperitoneal injected Fer-1 (Selleck, Houston, TX, USA); diabetic mice group (vehicle-P), who intraperitoneal injected 1% dimethyl sulfoxide (DMSO); diabetic mice group (As), who intragastric administrated Aspirin (Solarbio, Beijing, China); diabetic mice group (vehicle-G), who intragastric administrated 0.5% sodium carboxymethyl cellulose (Na-CMC; Solarbio, Beijing, China). Diabetes models were induced with 5 consecutive days of a single intraperitoneal injection of streptozotocin 40 mg/kg (dissolved in 0.1 M citrate buffer, pH 4.5; SigmaAldrich, St Louis, MO, USA). Control mice only was injected the same volume of citrate buffer. In the Fer-1 or vehicle-P groups, the diabetic mice were treated respectively with Fer-1 (2.5 umol/kg, dissolved in 1% DMSO) or 1% DMSO during the duration of treatment for 12-week every day. And in the AS and vehicle-G groups, the diabetic mice were treated respectively with aspirin (50 mg/kg, dissolved in 0.5% Na-CMC) or 0.5% Na-CMC for 12-week every day. REF000920 ICD-11: GB61.Z Diabetic kidney disease CELL00093 HK-2 Ferroptosis (hsa04216) Cell ferroptosis
unique01626 Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy. . . . Up regulation Suppressor Suppressor All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months. REF000842 ICD-11: GB61 Diabetic nephropathy CELL10129; CELL10097 Kidney tissues; HRGECs Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01628 Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy. . . . Up regulation Suppressor Suppressor All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months. REF000842 ICD-11: GB61 Diabetic nephropathy CELL10129; CELL10097 Kidney tissues; HRGECs Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01627 Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy. . . . Down regulation Driver Suppressor All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months. REF000842 ICD-11: GB61 Diabetic nephropathy CELL10129; CELL10097 Kidney tissues; HRGECs Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01154 Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice. . . . Up regulation Suppressor Suppressor Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established. REF000389 ICD-11: GB61 Diabetic nephropathy CELL00564 MPC5 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00402 Oxalate activates autophagy to induce ferroptosis of renal tubular epithelial cells and participates in the formation of kidney stones. Moreover, after oxalate treatment, overexpression of the BENC1 gene increased cell oxidative damage and ferroptosis. In addition, knockdown of NCOA4 reversed the effect of oxalate-induced ferroptosis in HK-2 cells. Inducer . Up regulation . . Driver Five-week-old male SD (Sprague-Dawley) rats (130-180 g) were used as experimental subjects. The control group had a normal diet, and the stone model group drank water containing 0.75% ethylene glycol. After feeding for one month, rats were sacrificed, and their kidneys were removed and subjected to silver nitrate staining, immunohistochemistry, and western blotting on the specimens of the normal control group and the kidney stone model group to explore the expression of NCOA4 in kidney stone model rats. REF000548 ICD-11: GB70 Kidney calculus CELL00093 HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00517 Astragaloside IV increased the phosphorylation of Pi3K, Akt, and the expression of Nrf2 and glutathione peroxidase 4 compared to HK-2 cells stimulated by ADR. In conclusion, ferroptosis may involve in Adriamycin (ADR)-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways. Suppressor . Up regulation . . Marker/Suppressor Male SD rats (200 ± 10 g) were obtained from Beijing Vital River Company (Beijing, China). They were kept under 12-h light/dark cycles and allowed free access to food and water. Rats were randomly divided into CON, ADR, ADR + ASIV, and ASIV groups (n = 6). Rats in ADR and ADR + ASIV groups received four equal injections of ADR intraperitoneally (4 mg/kg) in 5 weeks. Rats in ASIV and ADR + ASIV groups intragastrically received ASIV (10 mg/kg, daily) for 5weeks, while rats in CON and ADR groups were administered the same dose of solvent as ADR. Finally, the rats were euthanized, and the bilateral kidneys were excised. REF000706 ICD-11: GC2Z Adriamycin-induced renal damage CELL00093 HK-2 PI3K-Akt signaling pathway (hsa04151); Ferroptosis (hsa04216) Cell ferroptosis
unique01058 Silencing H19 downregulated Bcl-2 and GPX4 expression and upregulated Bax expression at both the mRNA and protein levels in HTR-8/SVneo trophoblast cells. In conclusion, the present findings suggested that H19 has important roles in spontaneous abortion (SA) by promoting apoptosis and ferroptosis. . . . Up regulation Suppressor Suppressor . REF000277 ICD-11: JA00 Spontaneous abortion CELL00310 HTR-8/SVneo Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01664 miR-2115-3p might interact with the GOT1 mRNA to downregulate its expression, further inhibiting the hypoxia-promoted ferroptosis in a preeclampsia model. . . . Down regulation Suppressor Driver Pregnant rats were randomly divided into 3 groups on gestational day 13, with 8 in each group: Sham group, PE group, and PE + ferrostatin-1 (FI) group. As previously mentioned, on gestational day 14, rats in the PE and PE + FI groups were subjected to reduced uterine perfusion pressure (RUPP) surgery to establish the PE model. Briefly, pregnant rats were anesthetized, sterilized with iodophor, and then opened. A contractile silver clip (0.203 mm) was placed on the aorta above the iliac bifurcation, as well as the bilateral uterine arcades at the end of the ovary were reduced with restrictive clips (0.100 mm) to the ovarian collaterals of the uterus. The rats in the Sham group were operated in a manner similar to the RUPP rats but were not clipped. On a gestational day 14, the mini-pumps were also inserted into the rat's peritoneum. The mini-pump in each rat of the PE + FI group was used to deliver FI at a dose of 10 mol/kg/d for 5 d. Systolic and diastolic blood pressure (SBP and DBP) were measured on gestational days 14, 16, and 19 using catheters inserted into the carotid artery and jugular vein. On a gestational day 19, urine, blood, and placenta of rats were collected for subsequent experiments. Urine protein content was detected using a commercial kit (C035-2, Nanjing Jiancheng, China). Plasma sFlt-1 content was detected by a commercial kit (ml059017, Mlbio, China). The remaining samples were stored at -80 . REF000870 ICD-11: 2F37.Y Preeclampsia CELL00310 HTR-8/SVneo Ferroptosis (hsa04216) Cell ferroptosis
unique00950 Abnormally up-regulated miR-30b-5p triggered the ferroptosis in trophoblasts under hypoxic conditions by down-regulating SLC7A11, Pax3, and Pax3-downstream target, FPN1. Blockage of miR-30b-5p up-regulation or direct inhibition of ferroptosis attenuated preeclampsia (PE) symptoms in the rat model, making miR-30b-5p a potential therapeutic target for preeclampsia. . . . Down regulation Driver Suppressor Pregnant SD rats were randomly dived into four groups: sham group (n = 8), PE group (n = 8), PE + ferrostatin-1 group ( n= 8), and PE + miR-30b-5p inhibition group (n = 8). On day 14 of pregnancy, PE rat model was established through reduced uterine perfusion pressure (RUPP) surgery, wherein constrictive silver clips were placed on the aorta (0.203-mm clips) superior to the iliac bifurcation and on the ovarian vessels (0.100-mm clips), according to a previous description. Sham rats were operated on in a fashion similar to that of RUPP rats, but without clipping. Mini-pumps were also intraperitoneally inserted into rats on day 14 of pregnancy. The mini-pump in each rat delivered the ferrostatin-1 at a dose of 10 umol/kg/day for 5 days. An miR-30b-5p antagonist (GenePharma) was injected from the tail veins on day 13 of gestation, at a rate of 100 uL/day for 6 days. The blood pressure was measured on days 14, 16, and 19 of gestation using catheters inserted into the carotid artery and jugular vein. REF000123 ICD-11: 2F37.Y Preeclampsia CELL00310; CELL10024 HTR-8/SVneo; TEV-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00951 Abnormally up-regulated miR-30b-5p triggered the ferroptosis in trophoblasts under hypoxic conditions by down-regulating SLC7A11, Pax3, and Pax3-downstream target, FPN1. Blockage of miR-30b-5p up-regulation or direct inhibition of ferroptosis attenuated preeclampsia (PE) symptoms in the rat model, making miR-30b-5p a potential therapeutic target for preeclampsia. . . . Up regulation Suppressor Suppressor Pregnant SD rats were randomly dived into four groups: sham group (n = 8), PE group (n = 8), PE + ferrostatin-1 group ( n= 8), and PE + miR-30b-5p inhibition group (n = 8). On day 14 of pregnancy, PE rat model was established through reduced uterine perfusion pressure (RUPP) surgery, wherein constrictive silver clips were placed on the aorta (0.203-mm clips) superior to the iliac bifurcation and on the ovarian vessels (0.100-mm clips), according to a previous description. Sham rats were operated on in a fashion similar to that of RUPP rats, but without clipping. Mini-pumps were also intraperitoneally inserted into rats on day 14 of pregnancy. The mini-pump in each rat delivered the ferrostatin-1 at a dose of 10 umol/kg/day for 5 days. An miR-30b-5p antagonist (GenePharma) was injected from the tail veins on day 13 of gestation, at a rate of 100 uL/day for 6 days. The blood pressure was measured on days 14, 16, and 19 of gestation using catheters inserted into the carotid artery and jugular vein. REF000123 ICD-11: 2F37.Y Preeclampsia CELL00310; CELL10024 HTR-8/SVneo; TEV-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01466 Panx1 and TLR4 are suggested to induce ferroptosis in Preeclampsia via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for Preeclampsia. . . . Down regulation Driver Suppressor . REF000695 ICD-11: 2F37.Y Preeclampsia CELL10095 Placental tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00949 Abnormally up-regulated miR-30b-5p triggered the ferroptosis in trophoblasts under hypoxic conditions by down-regulating SLC7A11, Pax3, and Pax3-downstream target, FPN1. Blockage of miR-30b-5p up-regulation or direct inhibition of ferroptosis attenuated preeclampsia (PE) symptoms in the rat model, making miR-30b-5p a potential therapeutic target for preeclampsia. . . . Down regulation Driver Suppressor Pregnant SD rats were randomly dived into four groups: sham group (n = 8), PE group (n = 8), PE + ferrostatin-1 group ( n= 8), and PE + miR-30b-5p inhibition group (n = 8). On day 14 of pregnancy, PE rat model was established through reduced uterine perfusion pressure (RUPP) surgery, wherein constrictive silver clips were placed on the aorta (0.203-mm clips) superior to the iliac bifurcation and on the ovarian vessels (0.100-mm clips), according to a previous description. Sham rats were operated on in a fashion similar to that of RUPP rats, but without clipping. Mini-pumps were also intraperitoneally inserted into rats on day 14 of pregnancy. The mini-pump in each rat delivered the ferrostatin-1 at a dose of 10 umol/kg/day for 5 days. An miR-30b-5p antagonist (GenePharma) was injected from the tail veins on day 13 of gestation, at a rate of 100 uL/day for 6 days. The blood pressure was measured on days 14, 16, and 19 of gestation using catheters inserted into the carotid artery and jugular vein. REF000123 ICD-11: 2F37.Y Preeclampsia CELL00310; CELL10024 HTR-8/SVneo; TEV-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01465 Panx1 and TLR4 are suggested to induce ferroptosis in Preeclampsia via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for Preeclampsia. . . . Down regulation Driver Suppressor . REF000695 ICD-11: 2F37.Y Preeclampsia CELL10095 Placental tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00976 Upregulated SIRT3-enhanced autophagy activation by promoting AMPK-mTOR pathway and decreasing GPX4 level to induce ferroptosis in trophoblastic cells. SIRT3 deficiency was resistant to high glucose- and erastin-induced autophagy-dependent ferroptosis and is, therefore, a potential therapeutic approach for treating gestational diabetes mellitus (GDM). . . . Down regulation Driver Suppressor . REF000167 ICD-11: JA63 Gestational diabetes mellitus CELL00310; CELL00607 HTR8/Svneo; Porcine trophectoderm (pTr) cell line Fatty acid metabolism (hsa01212); Autophagy (hsa04140); mTOR signaling pathway (hsa04150) Cell ferroptosis; Cell autophagy
unique00624 Echinatin (Ech) could mitigate Sev-induced apoptosis, oxidative stress, and ferroptosis in hippocampal neurons and hippocampus of rats by activating Nrf2 signalling. Moreover, Ech improved Sev-induced cognitive deficits in aged rats. These findings suggested that Ech may be developed as a neuroprotective agent to reduce postoperative cognitive dysfunction in the clinic. Suppressor . Up regulation . . Marker/Suppressor The Sprague-Dawley rats (male, 20-month-old, 550-700 g, n = 6 per group) were obtained from the Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijng, China). A total of 78 rats were used in animal experiments. Rats were allocated into the following five experimental groups: control, Sev, Sev + Ech (L), Sev + Ech (M), and Sev + Ech (H). Ech (Sigma-Aldrich; purity 98%) was given to rats by intraperitoneal injection as a single dose of 20 (L), 40 (M), or 80 mg/kg (H) at 1 h before Sev exposure. The injection volume of each rat was 5 mL. For control and Sev groups, an equal volume of vehicle was intraperitoneally injected into rats. Then, rats except for the control group were anaesthetised with 2% Sev (Sigma-Aldrich) for 5 h. The histological and biochemical analysis of the hippocampus was done 48 h later after the rats were sacrificed and the brains were removed. REF000853 ICD-11: MB21 Postoperative cognitive dysfunction CELL10175 Primary rat hippocampal neurons Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis
unique01623 In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis. . . . Down regulation Suppressor Driver . REF000841 ICD-11: MF8Y Immunoglobulin A nephropathy CELL10082 Human mesangial cells (HMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01625 In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis. . . . Down regulation Suppressor Driver . REF000841 ICD-11: MF8Y Immunoglobulin A nephropathy CELL10082 Human mesangial cells (HMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01622 In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis. . . . Up regulation Suppressor Suppressor . REF000841 ICD-11: MF8Y Immunoglobulin A nephropathy CELL10082 Human mesangial cells (HMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01624 In PPAR lentivirus-transfected HMCs stimulated by Gd-IgA1, ROS, MDA, and ACSL4 were decreased; glutathione and GPX4, and immunofluorescence colocalization of PPAR and GPX4, increased; and damaged mitochondria reduced. Hence, PPAR pathway downregulation can reduce FABP1 expression, affecting GPX4 and ACSL4 levels, causing HMC ferroptosis, and contributing to immunoglobulin A nephropathy (IgAN) pathogenesis. . . . Up regulation Suppressor Suppressor . REF000841 ICD-11: MF8Y Immunoglobulin A nephropathy CELL10082 Human mesangial cells (HMCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01523 Inhibition of miR-378a-3p expression reversed the reduction in GSH and the increase in lipid ROS levels induced by lead exposure. MiR-378a-3p exerted an important effect by regulating SLC7A11 expression in nerve injury induced by lead exposure. . . . Down regulation Driver Suppressor All the animals were housed in a temperature- and humidity-controlled room under a 12 h light/dark cycle and maintained in standard cages with free access to food and water. After seven days of breeding, the mice were randomly assigned to four groups of fifteen animals each. The animals in the four groups were treated with Pb acetate indrinking waterat doses of 0, 250 mg/L, 500 mg/L, and 1000 mg/L (control, LPb, MPb, and HPb groups, respectively). The Pb exposure period was 12 weeks. REF000742 ICD-11: NA04 Nerve injury CELL00549 HT22 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01198 Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis. Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. . . . Down regulation Suppressor Driver Eight-week-old male mice were subjected to severe CCI. Anesthesia was induced with 3% isoflurane in nitrous oxide: oxygen (7:3) and maintained with 1.5% isoflurane via nose cone. Temperature was maintained at 37 ± 0.5 using a heating blanket. After anesthesia, mice were placed in a stereotaxic frame (R.W.D. Shenzhen, China). A 4-mm-diameter craniotomy was performed over the left parietal bone and the bone flap was removed for trauma. A vertically directed CCI was applied (6.0 ± 0.2 m/s, 50 ms dwell time, 1.4 mm depth) using an impactor (R.W.D., Shenzhen, China). After the injury, the skin incision was closed. Mice were monitored with supplemental oxygen (100%) for 1h before returning to their cages. Fer-1 (1 mg/kg per day) was given i.p. at 7 days before CCI and once daily until euthanasia or the MWM test. Before the brain tissues were obtained, mice were perfused intracardially with 4 phosphate-buffer saline (PBS) solution. REF000450 ICD-11: NA07 Traumatic brain injury CELL10178; CELL10005 Primary cortical neuron; Brain tissues Ubiquitin mediated proteolysis (hsa04120); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00617 TFRC levels and ACSL4 levels were elevated after sevoflurane administration, suggesting that ferroptosis occurs in whole-brain regions of young rats after HIR and that sevoflurane aggravates the extent of ferroptosis. The results suggest that ferroptosis may mediate sevoflurane-aggravated young rats' brain injury induced by liver transplantation. Inducer . Up regulation . . Driver Sixty-four male Sprague-Dawley rats (2 weeks), weighing 20-30 g. All animals were brought from the Institute of Medical Laboratory Animals at the Chinese Academy of Medical Sciences and were kept in the same unit in a temperature-controlled environment [(22 ± 1) ]. The rats were fasted for 12 h before the experiment and drank water freely. After being numbered according to body weight, the rats were randomly divided into four groups using the random number table. The number of rats in each group was 16. The experimental groups were as follows: sham-operated group (S group, n = 16), the model group receiving HIR (HIR group, n = 16), sevoflurane group treated (HIR + Sev group, n = 16), and desferrioxamine treated group [deferoxamine (HIR + Sev + DFO) group, n = 16]. In HIR+Sev and HIR + Sev + DFO groups, rats were placed in an anesthetizing chamber and exposed to 3.6% sevoflurane (Cayman, 23996, USA) with complete oxygen for 2 h, and sham and HIR group rats were conducted with the same procedure without sevoflurane exposure. DFO (100 mg/kg, MCE, HY-B0988, China) was administered continuously daily for 6 days before surgery in the HIR + Sev + DFO group. Other groups were given equal amounts of saline. REF000844 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00667 Baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC. Suppressor . Down regulation . . Driver Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg). REF000895 ICD-11: NA07 Traumatic brain injury CELL10182 right hemispheres of rats Ferroptosis (hsa04216) Cell ferroptosis
unique00416 Baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Overall, baicalin suppressed autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage. Suppressor . Down regulation . . Driver Rats were injected with 4 mL/kg of chloral hydrate for anesthesia and then put on a stereotactic apparatus. Subsequently, the needle was tilted at 55 in the sagittal plane and fixed anterior to the bregma (7.5 mm). The needle tip was toward the right and lowered the anterior to the chiasma (2 mm). Finally, the nonheparinized autologous femoral arterial blood (0.3 mL) was injected into a prechiasmatic cistern using a syringe pump. Rat temperature was maintained at 37 ± 0.5 during the surgery. The rats in the sham group were injected with the same dose of saline into a prechiasmatic cistern. At last, rats were monitored for recovery and then returned to cages. REF000562 ICD-11: NA07 Traumatic brain injury CELL10181 Primary neurons Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00288 Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury. Ruxo significantly inhibited the expressions of COX2 and TfR1. In addition, Ruxo also reversed the lower expression of GPX4 caused by Traumatic brain injury. Suppressor . Down regulation . . Marker Adult male C57BL/6J mice (6-8 weeks, weighting 20-25 g) were used for all experiments. Mice were housed in pairs in a cage with access to food and water ad libitum. Mice were anesthetized with 4% chloral hydrate (0.4 mg/g) and mounted in a stereotaxic system (David Kopf Instruments, Tujunga, California). A midline skin incision was performed on the scalp to expose the skull, and a 5-mm craniotomy was made lateral to the sagittal suture and centered between bregma and lambda. The skull cap was then removed carefully to avoid destroying the dura mater. REF000408 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00928 Ferroptosis, a newly discovered form of iron-dependent regulated cell death, has been implicated in traumatic brain injury (TBI). Overexpression of miR-212-5p attenuated ferroptosis while downregulation of miR-212-5p promoted ferroptotic cell death partially by targeting prostaglandin-endoperoxide synthase-2 (Ptgs2) in HT-22 and Neuro-2a cell lines. . . . Down regulation Suppressor Marker Adult male C57BL/6J mice, aged 10-12 weeks and weighing 20 to 24 g. Briefly, following anesthesia with isoflurane (4% for induction and 12% for maintenance), mice were mounted on a stereotaxic frame. A midsagittal incision was performed in the scalp under sterile conditions and a 4.5 mm diameter circular craniotomy was made over the left parietotemporal cortex with a burr drill. Then, the skullcap was gently removed and a 3.0 mm diameter round and flat tip was carefully placed vertically to the dural surface. The electromagnetic controlled cortical impact device was set to 5.0 m/s for strike velocity, 2.0 mm for strike depth and 100 ms for dwell time. A sterile plastic film covered the bone window and intermittent sutures of the skin, and disinfection with iodophor were performed. The entire procedure required 15-30 min per mouse. REF000095 ICD-11: NA07 Traumatic brain injury CELL00549; CELL00552 HT22; Neuro-2a Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00478 Inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and early brain injury (EBI) in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen. Suppressor . Down regulation . . Driver Male Sprague-Dawley (SD) rats were introduced into research, for the present SAH model a total of 383 rats, weighing 250-300 g, were purchased from the Animal Center of Chongqing Medical University. The adult male SD rats assigned to SAH model procedures were randomly divided into several groups. The rats assigned to SAH model procedures were randomly divided into the groups, first to determine the expression of hepcidin, DMT1, FPN1, and GPX4, the main regulator of ferroptosis, and to subsequently select the most suitable timing for drug injections. Second, adult male SD rats were randomly divided into the groups to determine the significant preoperative doses of ebselen, heparin and OSM in terms of their effects on hepcidin, DMT1, FPN1, and GPX4 for further study. Lastly, male SD rats were randomly divided into the groups to determine the effects of hepcidin and DMT1 on iron metabolism, ferroptosis, and EBI, by using heparin, ebselen and OSM as the experimental interventions. REF000636 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00479 Inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and early brain injury (EBI) in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen. Inducer . Up regulation . . Driver Male Sprague-Dawley (SD) rats were introduced into research, for the present SAH model a total of 383 rats, weighing 250-300 g, were purchased from the Animal Center of Chongqing Medical University. The adult male SD rats assigned to SAH model procedures were randomly divided into several groups. The rats assigned to SAH model procedures were randomly divided into the groups, first to determine the expression of hepcidin, DMT1, FPN1, and GPX4, the main regulator of ferroptosis, and to subsequently select the most suitable timing for drug injections. Second, adult male SD rats were randomly divided into the groups to determine the significant preoperative doses of ebselen, heparin and OSM in terms of their effects on hepcidin, DMT1, FPN1, and GPX4 for further study. Lastly, male SD rats were randomly divided into the groups to determine the effects of hepcidin and DMT1 on iron metabolism, ferroptosis, and EBI, by using heparin, ebselen and OSM as the experimental interventions. REF000636 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00480 Inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and early brain injury (EBI) in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen. Inducer . Down regulation . . Marker/Suppressor Male Sprague-Dawley (SD) rats were introduced into research, for the present SAH model a total of 383 rats, weighing 250-300 g, were purchased from the Animal Center of Chongqing Medical University. The adult male SD rats assigned to SAH model procedures were randomly divided into several groups. The rats assigned to SAH model procedures were randomly divided into the groups, first to determine the expression of hepcidin, DMT1, FPN1, and GPX4, the main regulator of ferroptosis, and to subsequently select the most suitable timing for drug injections. Second, adult male SD rats were randomly divided into the groups to determine the significant preoperative doses of ebselen, heparin and OSM in terms of their effects on hepcidin, DMT1, FPN1, and GPX4 for further study. Lastly, male SD rats were randomly divided into the groups to determine the effects of hepcidin and DMT1 on iron metabolism, ferroptosis, and EBI, by using heparin, ebselen and OSM as the experimental interventions. REF000636 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00289 Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury. Ruxo significantly inhibited the expressions of COX2 and TfR1. In addition, Ruxo also reversed the lower expression of GPX4 caused by Traumatic brain injury. Suppressor . Down regulation . . Marker/Suppressor/Driver Adult male C57BL/6J mice (6-8 weeks, weighting 20-25 g) were used for all experiments. Mice were housed in pairs in a cage with access to food and water ad libitum. Mice were anesthetized with 4% chloral hydrate (0.4 mg/g) and mounted in a stereotaxic system (David Kopf Instruments, Tujunga, California). A midline skin incision was performed on the scalp to expose the skull, and a 5-mm craniotomy was made lateral to the sagittal suture and centered between bregma and lambda. The skull cap was then removed carefully to avoid destroying the dura mater. REF000408 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00616 TFRC levels and ACSL4 levels were elevated after sevoflurane administration, suggesting that ferroptosis occurs in whole-brain regions of young rats after HIR and that sevoflurane aggravates the extent of ferroptosis. The results suggest that ferroptosis may mediate sevoflurane-aggravated young rats' brain injury induced by liver transplantation. Inducer . Up regulation . . Marker/Suppressor/Driver Sixty-four male Sprague-Dawley rats (2 weeks), weighing 20-30 g. All animals were brought from the Institute of Medical Laboratory Animals at the Chinese Academy of Medical Sciences and were kept in the same unit in a temperature-controlled environment [(22 ± 1) ]. The rats were fasted for 12 h before the experiment and drank water freely. After being numbered according to body weight, the rats were randomly divided into four groups using the random number table. The number of rats in each group was 16. The experimental groups were as follows: sham-operated group (S group, n = 16), the model group receiving HIR (HIR group, n = 16), sevoflurane group treated (HIR + Sev group, n = 16), and desferrioxamine treated group [deferoxamine (HIR + Sev + DFO) group, n = 16]. In HIR+Sev and HIR + Sev + DFO groups, rats were placed in an anesthetizing chamber and exposed to 3.6% sevoflurane (Cayman, 23996, USA) with complete oxygen for 2 h, and sham and HIR group rats were conducted with the same procedure without sevoflurane exposure. DFO (100 mg/kg, MCE, HY-B0988, China) was administered continuously daily for 6 days before surgery in the HIR + Sev + DFO group. Other groups were given equal amounts of saline. REF000844 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00669 Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC. Suppressor Down regulation . . Driver . Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg). REF000895 ICD-11: NA07 Traumatic brain injury CELL10182 right hemispheres of rats Ferroptosis (hsa04216) Cell ferroptosis
unique00668 Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC. Suppressor Down regulation . . Driver . Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg). REF000895 ICD-11: NA07 Traumatic brain injury CELL10182 right hemispheres of rats Ferroptosis (hsa04216) Cell ferroptosis
unique00415 Baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Overall, baicalin suppressed autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage. Suppressor Down regulation . . Driver . Rats were injected with 4 mL/kg of chloral hydrate for anesthesia and then put on a stereotactic apparatus. Subsequently, the needle was tilted at 55 in the sagittal plane and fixed anterior to the bregma (7.5 mm). The needle tip was toward the right and lowered the anterior to the chiasma (2 mm). Finally, the nonheparinized autologous femoral arterial blood (0.3 mL) was injected into a prechiasmatic cistern using a syringe pump. Rat temperature was maintained at 37 ± 0.5 during the surgery. The rats in the sham group were injected with the same dose of saline into a prechiasmatic cistern. At last, rats were monitored for recovery and then returned to cages. REF000562 ICD-11: NA07 Traumatic brain injury CELL10181 Primary neurons Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00414 Baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Overall, baicalin suppressed autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage. Suppressor Down regulation . . Driver . Rats were injected with 4 mL/kg of chloral hydrate for anesthesia and then put on a stereotactic apparatus. Subsequently, the needle was tilted at 55 in the sagittal plane and fixed anterior to the bregma (7.5 mm). The needle tip was toward the right and lowered the anterior to the chiasma (2 mm). Finally, the nonheparinized autologous femoral arterial blood (0.3 mL) was injected into a prechiasmatic cistern using a syringe pump. Rat temperature was maintained at 37 ± 0.5 during the surgery. The rats in the sham group were injected with the same dose of saline into a prechiasmatic cistern. At last, rats were monitored for recovery and then returned to cages. REF000562 ICD-11: NA07 Traumatic brain injury CELL10181 Primary neurons Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00670 Our research suggests that baicalein inhibited ferroptosis after ROSC by targeting ALOX15. Iron content, and MDA were reduced. More importantly, baicalein alleviated ER stress by inhibiting the expression of GRP78, ATF4, and CHOP. Baicalein is a potential drug to relieve brain injury after ROSC. Suppressor Down regulation . . Driver . Healthy male Sprague-Dawley rats (weighing 370 g-420 g) were purchased from the Laboratory Animal Center of Sun Yat-sen University. The rats were randomized into five groups. Rats in sham group (n = 6) underwent the same anesthetic and surgical procedures, excluding cardiac arrest and CPR. All of the remaining four groups were given the interventions within 10 minutes of ROSC. Rats in CPR group (n = 6) received an intraperitoneal injection of 0.9% saline (1 mL/kg). Rats in baicalein group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein at the same time, based on previous studies. Rats in tunicamycin group (n = 6) were intraperitoneally injected with tunicamycin (2 mg/kg body weight) (22-24). Rats in baicalein + tunicamycin group (n = 6) were intraperitoneally injected with 50 mg/kg (body weight) baicalein and 2 mg/kg (body weight) tunicamycin. All groups were given the same volume of normal saline solvent (2 mL/kg). REF000895 ICD-11: NA07 Traumatic brain injury CELL10182 right hemispheres of rats Ferroptosis (hsa04216) Cell ferroptosis
unique00482 Vitamin B6 (VitB6) is a water-soluble vitamin and includes pyridoxine, pyridoxal, pyridoxamine, and their phosphorylated forms. VitB6 regulated the expression of LPS-induced apoptosis-related proteins and iron regulatory proteins. It mediated the expression of Nrf2, transcription factor NF-E2-related factor 2, which promoted the expression of antioxidant enzymes and restrained LPS-induced ferroptosis and apoptosis. Overall, VitB6 can be used on novel therapies to relieve LPS-induced myocardial injury. Suppressor . Up regulation . . Marker/Suppressor Male c57BL/6 mice (8 weeks old) were purchased from Beijing Wei Tong Li Hua Experimental Animal Technology Co. Ltd. (Beijing, China). Mice were divided into control (n = 8), LPS (n = 9), and VitB6+LPS (n = 9) groups. Mice were pretreated with PBS or VitB6 for 6 h and then treated with LPS (4 mg/kg) for 24 h. Cardiac ultrasound was performed before sacrifice. Inhaled isoflurane was given to mice for volatile anesthesia and the chest hair was removed with a depilatory cream. Then, mice were fixed on the warmed imaging platform and wore with the coupling agent. The Vevo2100 imaging system, equipped with a 40-MHz high-frequency transducer (VisualSonics Inc., Toronto, Canada), was applied to perform non-invasive examinations. The M-mode echocardiogram at the parasternal long axis was used to obtain the ejection fraction (EF) of left ventricular and fractional shortening (FS). REF000640 ICD-11: NB31 LPS-induced myocardial injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01442 Solute carrier family 7 member 11 (SLC7A11) is a downstream target of miR-140-5p, which induces ferroptosis via inhibition of GSH synthesis by targeting SLC7A11. Attenuating exosomal-miR-140-5p expression alleviates ferroptosis and obesity-induced cardiac injury by alleviating GSH inhibition. . . . Down regulation Driver Suppressor Six-week-old C57BL/6 male mice were randomly divided into two groups; the first group was fed a 45% high fat diet for 20 weeks while the control group were fed a normal chow diet. ATM-exosomes isolated from obese and lean mice were transferred into normal mice via tailvein injection(30 ug per week), as previously described. To investigate glutathione synthesis, 20 mM l-buthionine-(S,R)-sulfoximine (BSO) was added to the drinking water and administered to mice for 2 weeks. To inhibit ferroptosis, mice were given an intraperitoneal injection with Fer-1 (1 mg/kg). REF000681 ICD-11: NB31 Obesity-induced cardiac injury CELL00030 H9c2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01544 CircEXOC5 can enhance the stability of the target gene ACSL4 by binding to the RNA binding protein PTBP1 and up-regulate its expression, thereby promoting ferroptosis and exacerbating sepsis-induced acute lung injury. . . . Up regulation Driver Driver The sepsis mouse model was established by cecal ligation and puncture (CLP) of male C57BL/6 mouse (6-8 weeks, Guangzhou Animal Medical Center). Firstly, the mice were anesthetized by intraperitoneal injection of 4% chloral hydrate (0.1 ml/10g). The cecum was found by cutting a 1 cm longitudinally in the abdomen of the mice, and ligating the cecum from the end of the cecum to half the length of the ileocecal valve with 5-0 silk suture. Then a 21 G needle was used to puncture the ligature and the midpoint of the cecum once, and finally the wound was sutured. In the sham operation group, only laparotomy was performed, without ligation and perforation of the cecum. All animal-related experiments in this study were approved by hospital ethics committee according to following the Nation Institutes of Health Guide for the Laboratory Animals Care and Use (approval No. Med-Eth-Re [2022] 168). REF000760 ICD-11: 1G40-1G41 Sepsis causes acute lung injury CELL10132 MPVECs Ferroptosis (hsa04216) Cell ferroptosis
unique01543 CircEXOC5 can enhance the stability of the target gene ACSL4 by binding to the RNA binding protein PTBP1 and up-regulate its expression, thereby promoting ferroptosis and exacerbating sepsis-induced acute lung injury. . . . Up regulation Driver Driver The sepsis mouse model was established by cecal ligation and puncture (CLP) of male C57BL/6 mouse (6-8 weeks, Guangzhou Animal Medical Center). Firstly, the mice were anesthetized by intraperitoneal injection of 4% chloral hydrate (0.1 ml/10g). The cecum was found by cutting a 1 cm longitudinally in the abdomen of the mice, and ligating the cecum from the end of the cecum to half the length of the ileocecal valve with 5-0 silk suture. Then a 21 G needle was used to puncture the ligature and the midpoint of the cecum once, and finally the wound was sutured. In the sham operation group, only laparotomy was performed, without ligation and perforation of the cecum. All animal-related experiments in this study were approved by hospital ethics committee according to following the Nation Institutes of Health Guide for the Laboratory Animals Care and Use (approval No. Med-Eth-Re [2022] 168). REF000760 ICD-11: 1G40-1G41 Sepsis causes acute lung injury CELL10132 MPVECs Ferroptosis (hsa04216) Cell ferroptosis
unique00607 Astragaloside IV (Ast-IV) reduced the lung wet-dry ratio and the levels of interleukin 6 (IL-6), tumor necrosis factor- (TNF-) and interleukin 1 (IL-1) in serum. Ast-IV could also improve the oxidative stress level in BALF, restore the GSH level in the lung tissue, and reduce the iron content in the lung tissue. Western blot outcomes revealed that Ast-IV regulated the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to protect PM2.5-mediated lung injury. Suppressor . Up regulation . . Suppressor The animals were randomly assigned to six groups (7 mice in each) as follows: (I) Normal saline (NS) group, (II) Ast-IV 100 mg/kg (Ast) group, (III) PM2.5 group, (IV) Ast-IV 50 mg/kg + PM2.5 (Ast-L) group, (V) Ast 100 mg/kg + PM2.5 (Ast-H) group, and (VI) Ast-IV 100 mg/kg + erastin 20 mg/kg + PM2.5 (Era) group. Based on our previous results, this study adopted anintraperitoneal injection(i.p.) of Ast-IV (dissolved in normal saline containing 0.1% DMSO for preventive treatment. After all the mice were adaptively fed for 5 days, in the NS and PM2.5 groups, mice received the normal saline containing 0.1% DMSO viai.p.once a day for the next three consecutive days. Similar to the NS group, in the Ast, Ast-H, and Era groups, mice received Ast-IV (100 mg/kg) viai.p. Ast-L group received Ast-IV (50 mg/kg) viai.p. To evaluate the effect of Ast-IV on ferroptosis in PM2.5-induced lung injury, we used the ferroptosis agonist erastin to activate ferroptosisin vivo. In the Era group, mice received erastin (20 mg/kg, 10% DMSO + 40% PEG300 + 5%Tween80 + 45% normal saline) 30 min before each preventive treatment of Ast-IV. REF000832 ICD-11: NB32 Lung injury CELL10045 SRM 2786(PM2.5 Ferroptosis (hsa04216) Cell ferroptosis
unique01588 Inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. And inhibiting MUC1 reversed the alleviating effect of vitamin E on acute lung injury caused by sepsis. . . . Up regulation Suppressor Marker/Suppressor C57BL/6J male mice (6-8 weeks) were purchased from Slac Lab Animals (Shanghai, China). The basic principle of the CLP method was to find the caecum through anatomy and puncture at the blind end and extrude the contents into the abdominal cavity. Diffuse peritonitis was formed, and systemic infection appeared in mice. Mice in the control group were only treated with laparotomy. REF000794 ICD-11: NB32 Acute lung injury CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00094 The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues. Inducer . Down regulation . . Suppressor The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. REF000148 ICD-11: NB32 Acute lung injury CELL00076 BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00096 The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues. Suppressor . Up regulation . . Suppressor The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. REF000148 ICD-11: NB32 Acute lung injury CELL00076 BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00268 Sevoflurane (Sev) could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced acute lung injury (ALI) to a certain extent. Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia. Suppressor . Up regulation . . Driver/Suppressor Male C57BL/6 mice (8 weeks, 23-25 g) were obtained from Beijing Hua Fu Kang Biotechnology Co. LTD (Beijing, China). A total of 96 mice were randomly divided into 6 groups (n = 16 per group): Sham group, LPS group, Fer-1 group, Fe group, Sev group, and Fe + Sev group. Mice were given 5 mg/kg LPS intranasally to construct LPS-induced ALI model. To study the role of ferroptosis in ALI, the mice in the Fer-1 or Fe groups were administered with Fer-1 (0.8 mg/kg; Ferrostatin-1, the inhibitor of ferroptosis) or Fe (8 mg/kg; Fe-citrate (III), ferroptosis inducer) via tail vein injection once a day for 3 consecutive days before treatment with LPS, respectively. To study the effect of Sev on ALI mice, the mice in Sev group were treated with LPS for 2 h, and then Sev, delivered by gaseous admixture (oxygen) at a concentration of 3% via a calibrated vaporizer, was administered via an endotracheal tube for 4 h. In order to study the effect of Sev on ferroptosis, the mice in Fe + Sev group were administered with Fe via tail vein injection once a day for 3 consecutive days, and then treated with LPS and Sev. Sham group was given 0.9% NaCl (containing 0.1% DMSO). REF000368 ICD-11: NB32 Acute lung injury CELL00076 BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00605 Astragaloside IV (Ast-IV) reduced the lung wet-dry ratio and the levels of interleukin 6 (IL-6), tumor necrosis factor- (TNF-) and interleukin 1 (IL-1) in serum. Ast-IV could also improve the oxidative stress level in BALF, restore the GSH level in the lung tissue, and reduce the iron content in the lung tissue. Western blot outcomes revealed that Ast-IV regulated the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to protect PM2.5-mediated lung injury. Suppressor . Up regulation . . Marker/Suppressor The animals were randomly assigned to six groups (7 mice in each) as follows: (I) Normal saline (NS) group, (II) Ast-IV 100 mg/kg (Ast) group, (III) PM2.5 group, (IV) Ast-IV 50 mg/kg + PM2.5 (Ast-L) group, (V) Ast 100 mg/kg + PM2.5 (Ast-H) group, and (VI) Ast-IV 100 mg/kg + erastin 20 mg/kg + PM2.5 (Era) group. Based on our previous results, this study adopted anintraperitoneal injection(i.p.) of Ast-IV (dissolved in normal saline containing 0.1% DMSO for preventive treatment. After all the mice were adaptively fed for 5 days, in the NS and PM2.5 groups, mice received the normal saline containing 0.1% DMSO viai.p.once a day for the next three consecutive days. Similar to the NS group, in the Ast, Ast-H, and Era groups, mice received Ast-IV (100 mg/kg) viai.p. Ast-L group received Ast-IV (50 mg/kg) viai.p. To evaluate the effect of Ast-IV on ferroptosis in PM2.5-induced lung injury, we used the ferroptosis agonist erastin to activate ferroptosisin vivo. In the Era group, mice received erastin (20 mg/kg, 10% DMSO + 40% PEG300 + 5%Tween80 + 45% normal saline) 30 min before each preventive treatment of Ast-IV. REF000832 ICD-11: NB32 Lung injury CELL10045 SRM 2786(PM2.5 Ferroptosis (hsa04216) Cell ferroptosis
unique01587 Inhibition of MUC1 dimerization could increase the expression level of Keap1, reduce the phosphorylation level of GSK3, inhibit the entry of Nrf2 into the nucleus, further inhibit the expression level of GPX4, enhance the lipid peroxidation level of lung tissues, trigger ferroptosis, and aggravate lung injury. And inhibiting MUC1 reversed the alleviating effect of vitamin E on acute lung injury caused by sepsis. . . . Up regulation Suppressor Marker/Suppressor C57BL/6J male mice (6-8 weeks) were purchased from Slac Lab Animals (Shanghai, China). The basic principle of the CLP method was to find the caecum through anatomy and puncture at the blind end and extrude the contents into the abdominal cavity. Diffuse peritonitis was formed, and systemic infection appeared in mice. Mice in the control group were only treated with laparotomy. REF000794 ICD-11: NB32 Acute lung injury CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01255 JMJD3 ( KDM6B) deficiency may relieve LPS-induced acute lung injury (ALI) by blocking alveolar epithelial ferroptosis in a Nrf2 dependent manner, which may serve as a novel therapeutic target against ALI. . . . Down regulation Driver Marker/Suppressor A total of 30 male C57/B6J mice (8-10 weeks, 21-23 g) were acquired from Chinese Academy of Medical Sciences (Beijing, China). The sepsis-induced ALI model was constructed by administering LPS intratracheally (5 mg/kg) for 12 h as previously reported. The control groups were given an isovolumetric sterile saline. Then, 12 h after LPS installation, the animals were sacrificed by cervical dislocation under deep anesthesia with an intraperitoneal injection of 2% sodium pentobarbital (60 mg/kg). REF000505 ICD-11: NB32 Acute lung injury CELL00045; CELL00605 A549; AT2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01538 STAT6 negatively regulates ferroptosis through competitively binding with CBP, which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression. Finally, pulmonary-specific STAT6 overexpression decreased the ferroptosis and attenuated CS and LPS induced acute lung injury. . . . Up regulation Suppressor Suppressor For the models of CS and LPS exposure, mice were anesthetized and intratracheally instilled with CS suspensions (3 mg/50 ul) or LPS (1 mg/kg). For the models of CS + Ferr-1/DFO, mice were intraperitoneally injected with Ferr-1 (1.25 umol/kg) or intranasal instilled with DFO (10 mg/kg) for 7 consecutive days after CS instillation. For the models of LPS + Ferr-1/DFO, mice were pretreated with Ferr-1 or DFO for 2 consecutive days and then intratracheally instilled with LPS. Mice were sacrificed 24 h after LPS instillation. For the X-ray exposure model, mice were exposed to ionizing radiation (IR) at 20 Gy, which was delivered at the dose rate of 2 Gy/min and a source skin distance of 51 cm by an X-ray generator (Model X-RAD320iX; Precision X-Ray, Inc., North Branford, CT, USA), and sacrificed 3 days after radiation. REF000754 ICD-11: NB32 Acute lung injury CELL00038; CELL00085 THP-1; HBE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01537 STAT6 negatively regulates ferroptosis through competitively binding with CBP, which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression. Finally, pulmonary-specific STAT6 overexpression decreased the ferroptosis and attenuated CS and LPS induced acute lung injury. . . . Up regulation Suppressor Suppressor For the models of CS and LPS exposure, mice were anesthetized and intratracheally instilled with CS suspensions (3 mg/50 ul) or LPS (1 mg/kg). For the models of CS + Ferr-1/DFO, mice were intraperitoneally injected with Ferr-1 (1.25 umol/kg) or intranasal instilled with DFO (10 mg/kg) for 7 consecutive days after CS instillation. For the models of LPS + Ferr-1/DFO, mice were pretreated with Ferr-1 or DFO for 2 consecutive days and then intratracheally instilled with LPS. Mice were sacrificed 24 h after LPS instillation. For the X-ray exposure model, mice were exposed to ionizing radiation (IR) at 20 Gy, which was delivered at the dose rate of 2 Gy/min and a source skin distance of 51 cm by an X-ray generator (Model X-RAD320iX; Precision X-Ray, Inc., North Branford, CT, USA), and sacrificed 3 days after radiation. REF000754 ICD-11: NB32 Acute lung injury CELL00038; CELL00085 THP-1; HBE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00606 Astragaloside IV (Ast-IV) reduced the lung wet-dry ratio and the levels of interleukin 6 (IL-6), tumor necrosis factor- (TNF-) and interleukin 1 (IL-1) in serum. Ast-IV could also improve the oxidative stress level in BALF, restore the GSH level in the lung tissue, and reduce the iron content in the lung tissue. Western blot outcomes revealed that Ast-IV regulated the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to protect PM2.5-mediated lung injury. Suppressor . Up regulation . . Suppressor The animals were randomly assigned to six groups (7 mice in each) as follows: (I) Normal saline (NS) group, (II) Ast-IV 100 mg/kg (Ast) group, (III) PM2.5 group, (IV) Ast-IV 50 mg/kg + PM2.5 (Ast-L) group, (V) Ast 100 mg/kg + PM2.5 (Ast-H) group, and (VI) Ast-IV 100 mg/kg + erastin 20 mg/kg + PM2.5 (Era) group. Based on our previous results, this study adopted anintraperitoneal injection(i.p.) of Ast-IV (dissolved in normal saline containing 0.1% DMSO for preventive treatment. After all the mice were adaptively fed for 5 days, in the NS and PM2.5 groups, mice received the normal saline containing 0.1% DMSO viai.p.once a day for the next three consecutive days. Similar to the NS group, in the Ast, Ast-H, and Era groups, mice received Ast-IV (100 mg/kg) viai.p. Ast-L group received Ast-IV (50 mg/kg) viai.p. To evaluate the effect of Ast-IV on ferroptosis in PM2.5-induced lung injury, we used the ferroptosis agonist erastin to activate ferroptosisin vivo. In the Era group, mice received erastin (20 mg/kg, 10% DMSO + 40% PEG300 + 5%Tween80 + 45% normal saline) 30 min before each preventive treatment of Ast-IV. REF000832 ICD-11: NB32 Lung injury CELL10045 SRM 2786(PM2.5 Ferroptosis (hsa04216) Cell ferroptosis
unique01313 Nrf2 can negatively regulate ferroptosis via modulation of TERT and SLC7A11 levels. Overexpression of TERT (OETERT) alleviates ferroptosis via modulation of SLC7A11. The conclusion from this study brings insight into new candidates that can be targeted in future ischemia/reperfusion-induced acute lung injury (IIR-ALI) therapy. . . . Up regulation Suppressor Suppressor We received 60 C57BL/6J mice and 48 Nrf2 knockout (Nrf2-/-) mice of the same genetic background from the RIKEN Bio-Resource Centre via the National BioResource Project, MEXT, Japan. Intestinal ischemia was simulated by clamping the superior mesenteric artery following the intraperitoneal administration of 50 mg/kg sodium pentobarbital. Forty-five minutes later, the intestine was allowed to re-perfuse for 3 h. REF000567 ICD-11: NB32 Acute lung injury CELL00557 MLE12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
dupunique01537 STAT6 negatively regulates ferroptosis through competitively binding with CBP, which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression. Finally, pulmonary-specific STAT6 overexpression decreased the ferroptosis and attenuated CS and LPS induced acute lung injury. . . . Down regulation Driver Suppressor For the models of CS and LPS exposure, mice were anesthetized and intratracheally instilled with CS suspensions (3 mg/50 ul) or LPS (1 mg/kg). For the models of CS + Ferr-1/DFO, mice were intraperitoneally injected with Ferr-1 (1.25 umol/kg) or intranasal instilled with DFO (10 mg/kg) for 7 consecutive days after CS instillation. For the models of LPS + Ferr-1/DFO, mice were pretreated with Ferr-1 or DFO for 2 consecutive days and then intratracheally instilled with LPS. Mice were sacrificed 24 h after LPS instillation. For the X-ray exposure model, mice were exposed to ionizing radiation (IR) at 20 Gy, which was delivered at the dose rate of 2 Gy/min and a source skin distance of 51 cm by an X-ray generator (Model X-RAD320iX; Precision X-Ray, Inc., North Branford, CT, USA), and sacrificed 3 days after radiation. REF000754 ICD-11: NB32 Acute lung injury CELL00038; CELL00085 THP-1; HBE Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00093 The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues. Inducer . Down regulation . . Suppressor The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. REF000148 ICD-11: NB32 Acute lung injury CELL00076 BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00095 The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues. Suppressor . Up regulation . . Suppressor The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. REF000148 ICD-11: NB32 Acute lung injury CELL00076 BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01435 Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury. Inducer Up regulation . . Driver . . REF000677 ICD-11: NB32 Acute lung injury CELL00557 MLE12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
dupunique01435 Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury. Inducer Up regulation . . Driver . . REF000677 ICD-11: NB32 Acute lung injury CELL00557 MLE12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00794 Epigallocatechin-3-Gallate (EGCG) supplementation alleviated the liver oxidative damage caused by iron overload by inhibiting ferroptosis. EGCG addition increased NRF2 and GPX4 expression and elevated antioxidant capacity in iron overload mice. EGCG administration attenuates iron metabolism disorders by upregulating FTH/FTL expression. Through these two mechanisms, EGCG can effectively inhibit iron overload-induced ferroptosis. Suppressor . Up regulation . . Marker/Suppressor All mice were randomly divided into a 2 x 2 factorial arrangement, fed diets containing 40 mg/kg or 5000 mg/kg FeSO4 (the basis of the diet was AIN-93), and gavaged with PBS or 50 mg EGCG/kg body weight per day, respectively. The experiment lasted for 6 weeks, including a 1-week adaptation and a 3-week EGCG gavage; then, all mice were euthanized. REF001015 ICD-11: NB91 Liver Oxidative Damage CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00801 Quercetin (QCT) specifically reacted with autophagic cargo receptor NCOA4, blocked the degradation of iron storage protein FTH1, and eventually downregulated the intracellular iron levels and the consequent ferroptosis. Collectively, our results presented a unique approach to alleviate ACR-induced liver injury by targeting ferroptosis with QCT. Suppressor . Up regulation . . Marker/Suppressor Six-week-old male C57BL/6J mice (18-20 g) were obtained from Zhejiang Vital River Laboratory (Zhejiang, China). 32 mice were divided randomly into 4 groups: Saline group (CONT), 25 mg/kg/day ACR group (ACR), 25 mg/kg/day ACR with a low dose of 25 mg/kg/day QCT group (ACR + QCT (L)), and 25 mg/kg/day ACR with a high dose of 50 mg/kg/day QCT group (ACR + QCT (H)), 8 animals in each group. REF001018 ICD-11: NB91 Liver injury CELL00048 HepG2 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique00795 Epigallocatechin-3-Gallate (EGCG) supplementation alleviated the liver oxidative damage caused by iron overload by inhibiting ferroptosis. EGCG addition increased NRF2 and GPX4 expression and elevated antioxidant capacity in iron overload mice. EGCG administration attenuates iron metabolism disorders by upregulating FTH/FTL expression. Through these two mechanisms, EGCG can effectively inhibit iron overload-induced ferroptosis. Suppressor . Up regulation . . Suppressor All mice were randomly divided into a 2 x 2 factorial arrangement, fed diets containing 40 mg/kg or 5000 mg/kg FeSO4 (the basis of the diet was AIN-93), and gavaged with PBS or 50 mg EGCG/kg body weight per day, respectively. The experiment lasted for 6 weeks, including a 1-week adaptation and a 3-week EGCG gavage; then, all mice were euthanized. REF001015 ICD-11: NB91 Liver Oxidative Damage CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00592 Bicyclol exerted its hepatoprotection by preventing the aforesaid ferroptotic process. Furthermore, bicyclol alleviated erastin-induced cellular inviability, destruction, and lipid peroxidation in vitro. Knockdown of GPX4 diminished these protective activities against perturbations associated with ferroptosis in L-O2 hepatocytes. Additionally, Nrf2 silencing drastically reduced GPX4 levels, and further impeded the medicinal effects of bicyclol. In summary, positively regulating Nrf2-GPX4 axis by bicyclol can prevent ferroptosis in CCl4-induced acute liver injury in mice. Suppressor . Up regulation . . Suppressor The mice were treated with intraperitoneal administration (i.p.) of oil (control group) or a mixture of CCl4 (50%) and oil (50%) at a dosage of 2 ml/kg body weight. In the bicyclol-treated group, mice accepted administration of 200 mg/kg (using 0.5% carboxymethyl cellulose as solvent) by gavage three times a day 1 h before CCl4 exposure, while other groups accepted vehicles of the equal volume. Fer-1 was prepared in DMSO (5 mg/kg), andi.p. injected into mice once 1 h before CCl4 exposure. The dosage of bicyclol was consistent with our previous work. The mice were then sacrificed to collect liver and serum samples after 24 or 48 h. REF000823 ICD-11: NB91 CCl4-induced iver injury CELL00304 L-02 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00681 Disulfiram (DSF) is conjugated to multiple cysteine residues in GPX4 and disrupts GPX4 interaction with HSC70, an adaptor protein for chaperone mediated autophagy, thus preventing GPX4 degradation induced by erastin. In addition, DSF ameliorates concanavalin A induced acute liver injury by suppressing ferroptosis in a mouse model. Suppressor . Up regulation . . Suppressor C57BL/6J male mice aged 8 weeks were purchased from Charles River Laboratories International, Inc., and housed in a specific pathogen-free animal facility. DMSO or DSF (21 mg/kg) was injected intraperitoneally into mice for 0.5 h, followed by ConA injection via the tail vein at 15 mg/kg. Mice were sacrificed at 24 h post ConA injection. Liver and blood samples were collected at this time point for H&E staining, IHC staining, and measurement of AST/ALT (Dian Diagnostics Co., Ltd). REF000904 ICD-11: NB91 Acute liver injury CELL00095; CELL00057; CELL00021; CELL00151; CELL00125; CELL00299; CELL00005; CELL00469 HT1080; HEK293T; 786-O; 769-P; SK-HEP-1; HCCLM3; MDA-MB-231; MDA231-LM2-4175 Ferroptosis (hsa04216) Cell ferroptosis
unique00793 Epigallocatechin-3-Gallate (EGCG) supplementation alleviated the liver oxidative damage caused by iron overload by inhibiting ferroptosis. EGCG addition increased NRF2 and GPX4 expression and elevated antioxidant capacity in iron overload mice. EGCG administration attenuates iron metabolism disorders by upregulating FTH/FTL expression. Through these two mechanisms, EGCG can effectively inhibit iron overload-induced ferroptosis. Suppressor . Up regulation . . Suppressor All mice were randomly divided into a 2 x 2 factorial arrangement, fed diets containing 40 mg/kg or 5000 mg/kg FeSO4 (the basis of the diet was AIN-93), and gavaged with PBS or 50 mg EGCG/kg body weight per day, respectively. The experiment lasted for 6 weeks, including a 1-week adaptation and a 3-week EGCG gavage; then, all mice were euthanized. REF001015 ICD-11: NB91 Liver Oxidative Damage CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00735 Kaempferol (KA) activated the Nrf2 pathway and upregulated Gpx4 in mouse livers and L02 cells to inhibit ferroptosis induced by APAP. Finally, molecular docking indicated the potential interaction of KA with Keap1. Taken together, KA ameliorated oxidative stress and ferroptosis-mediated acetaminophen-induced liver injury by activating Nrf2 signaling. Suppressor . Up regulation . . Suppressor Male BALB/c mice (8-week-old, 20-22 g) were purchased from Guangdong Medical Laboratory Animal Center (Guangzhou, China). The experimental animals were fed adaptively for one week in the Experimental Animal Center of Guangdong Pharmaceutical University (Guangzhou, China). Feeding conditions were set at 26 , humidity 65% and a lightdark cycle for 12 hours. All animal experiments were performed following the Guide for the Care and Use of Laboratory Animals, and the procedures were approved by the Research Ethical Committee of Guangdong Pharmaceutical University (gdpulacspf2020007). REF000958 ICD-11: NB91 Liver injury CELL00304 L-02 Ferroptosis (hsa04216) Cell ferroptosis
unique00590 Schisandrin B (SchB) increased the levels of SOD, GSH, GSH-px, CAT, and T-AOC, decreased the level of MDA, and inhibited the abnormal oxidative stress in the liver. And SchB as a natural molecule depends on reducing the level of oxidative stress, thereby inhibiting lipid peroxidation, ferroptosis, and apoptosis. The expression of NRF2, GPX4, SOD2, and Bcl-2/Bax decreased, while the expression of NOX2/4 and cleaved caspase-3 increased in pirarubicin-treated hepatocytes. However, the above changes were significantly reversed after SchB or Fer-1 treatment. SchB has obvious protective effect on pirarubicin-induced hepatotoxicity. Suppressor . Up regulation . . Suppressor A total of 40 male SD rats (180~200 g, 6~8 weeks) were purchased from the CMU experimental animal center. The rats were randomly divided into four groups: control (CON) group (normal diet rats were injected with equal volume of normal saline through caudal vein once a week, n = 10), SchB group (SchB diet rats, 50 mg/kg/day, were injected with equal volume of normal saline through caudal vein once a week, n = 10), THP group (normal diet rats were injected with 3 mg/kg/day THP through caudal vein once a week, n = 10), and SchB+THP group (SchB diet rats, 50 mg/kg/day, were injected with 3 mg/kg/day THP through caudal vein once a week, n = 10). CON and THP rats were fed an AIN-76A feed (12.4% fat, 68.8% carbohydrate, and 18.8% protein). SchB and SchB+THP rats were fed an SchB feed (approximately 0.5 SchB was added into AIN-76A feed). After conversion, 0.5 SchB in feed = 50 mg/kg in rats. REF000817 ICD-11: NB91 Pirarubicin-induced hepatotoxicity CELL10179 Primary hepatocyte Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00529 DEHP caused oxidative stress and increased the Fe2+ content, finally resulting in ferroptosis in AML12 cells. Apigenin restrained the toxicity of DEHP and antagonized DEHP-induced ferroptosis in AML12 cells. The protective effects of APG on DEHP-induced liver injury were achieved by activating GPX4 and suppressing intracellular iron accumulation. Suppressor . Up regulation . . Suppressor . REF000732 ICD-11: NB91 DEHP-induced liver injury CELL00541 AML12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00601 Astaxanthin reduced inflammation through the NF-B pathway, inhibited oxidative stress and ferroptosis, and increased autophagy through the Nrf2/HO-1 pathway, ameliorating acetaminophen-induced liver injury in vivo and in vitro. Suppressor . Up regulation . . Suppressor Mice were randomly divided into four groups as follows (n = 5): (1) control, (2) APAP (MCE, Monmouth Junction, NJ, USA), (3) olive oil + APAP (oil + APAP), and (4) ASX (Energy Chemical, Shanghai, China) dissolved in olive oil + APAP (ASX + APAP). Astaxanthin was dissolved in olive oil to obtain a mixture of 20 mg/mL. Mice in groups 3 and 4 were given a dose of olive oil and a mixture of 5 mL/kgBW by gavage every day for 2 weeks. On day 15, mice in groups 2, 3, and 4 were given a peritoneal injection of 500 mg/kg APAP to induce liver injury. The mice were fasted for 12 h before the administration of APAP. Ten hours after APAP administration, blood and liver tissue were collected for further examination and analyses. Blood was centrifuged to obtain supernatants,which were stored at -80. Liver tissues were immediately removed from each animal, and homogenates were processed with formaldehyde and glutaraldehyde for protein and histological analysis. REF000828 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL00304 L-02 NF-kappa B signaling pathway (hsa04064); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00339 Ulinastatin plays a role in mitigation of APAP-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression. Suppressor . Up regulation . . Suppressor Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection. REF000464 ICD-11: NB91 Liver injury CELL00304 LO2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00769 APAP could increase malondialdehyde (MDA) and Fe2+ levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced liver injury, NF-B activation and increased the expression of Nrf2 and HO-1. Suppressor . Up regulation . . Suppressor APAP-induced liver injury model was induced byintraperitoneal injection 300 mg/kg APAP. The mice of APAP + abietic acid (10, 20, 40 mg/kg) were given abietic acid by intraperitoneal injection 1 h before APAP treatment. The doses of abietic acid used in this study were based on previous studies. Twelve hours later, the mice were sacrificed after anesthesia with 1%pentobarbital (50 mg/kg) injected intraperitoneally and the samples were collected. REF000991 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL00541 AML12 Ferroptosis (hsa04216) Cell ferroptosis
unique00800 Quercetin (QCT) specifically reacted with autophagic cargo receptor NCOA4, blocked the degradation of iron storage protein FTH1, and eventually downregulated the intracellular iron levels and the consequent ferroptosis. Collectively, our results presented a unique approach to alleviate ACR-induced liver injury by targeting ferroptosis with QCT. Suppressor . Inhibit function . . Driver Six-week-old male C57BL/6J mice (18-20 g) were obtained from Zhejiang Vital River Laboratory (Zhejiang, China). 32 mice were divided randomly into 4 groups: Saline group (CONT), 25 mg/kg/day ACR group (ACR), 25 mg/kg/day ACR with a low dose of 25 mg/kg/day QCT group (ACR + QCT (L)), and 25 mg/kg/day ACR with a high dose of 50 mg/kg/day QCT group (ACR + QCT (H)), 8 animals in each group. REF001018 ICD-11: NB91 Liver injury CELL00048 HepG2 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique00970 iASPP (PPP1R13L) mediated its protective effects against acute lung injury through the Nrf2/HIF-1/TF signaling pathway. Ferroptosis contributes to intestinal ischemia/reperfusion-induced acute lung injury (ALI), and iASPP treatment inhibits ferroptosis in part via Nrf2. . . . Up regulation Suppressor Marker/Suppressor 8-week-old Nrf2-knockout (Nrf2-/-) and wild-type (WT) littermate male mice on a C57BL/6J background (provided by the RIKEN Bio-Resource Center through the National Bio-Resource Project of MEXT, Japan) were used for in vivo experiments. Intestinal ischemia was induced by clamping of the superior mesenteric artery after the intraperitoneal injection of 50 mg/kg of sodium pentobarbital. After 90 min, the intestine was reperfused for the times indicated. Sham control mice underwent the same procedure without vascular occlusion. REF000153 ICD-11: NB91 Acute liver injury CELL10131; CELL10134 MLE-2; Lung tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00600 Astaxanthin reduced inflammation through the NF-B pathway, inhibited oxidative stress and ferroptosis, and increased autophagy through the Nrf2/HO-1 pathway, ameliorating acetaminophen-induced liver injury in vivo and in vitro. Suppressor . Up regulation . . Marker/Suppressor Mice were randomly divided into four groups as follows (n = 5): (1) control, (2) APAP (MCE, Monmouth Junction, NJ, USA), (3) olive oil + APAP (oil + APAP), and (4) ASX (Energy Chemical, Shanghai, China) dissolved in olive oil + APAP (ASX + APAP). Astaxanthin was dissolved in olive oil to obtain a mixture of 20 mg/mL. Mice in groups 3 and 4 were given a dose of olive oil and a mixture of 5 mL/kgBW by gavage every day for 2 weeks. On day 15, mice in groups 2, 3, and 4 were given a peritoneal injection of 500 mg/kg APAP to induce liver injury. The mice were fasted for 12 h before the administration of APAP. Ten hours after APAP administration, blood and liver tissue were collected for further examination and analyses. Blood was centrifuged to obtain supernatants,which were stored at -80. Liver tissues were immediately removed from each animal, and homogenates were processed with formaldehyde and glutaraldehyde for protein and histological analysis. REF000828 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL00304 L-02 NF-kappa B signaling pathway (hsa04064); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy; Cell apoptosis
unique00591 Bicyclol exerted its hepatoprotection by preventing the aforesaid ferroptotic process. Furthermore, bicyclol alleviated erastin-induced cellular inviability, destruction, and lipid peroxidation in vitro. Knockdown of GPX4 diminished these protective activities against perturbations associated with ferroptosis in L-O2 hepatocytes. Additionally, Nrf2 silencing drastically reduced GPX4 levels, and further impeded the medicinal effects of bicyclol. In summary, positively regulating Nrf2-GPX4 axis by bicyclol can prevent ferroptosis in CCl4-induced acute liver injury in mice. Suppressor . Up regulation . . Marker/Suppressor The mice were treated with intraperitoneal administration (i.p.) of oil (control group) or a mixture of CCl4 (50%) and oil (50%) at a dosage of 2 ml/kg body weight. In the bicyclol-treated group, mice accepted administration of 200 mg/kg (using 0.5% carboxymethyl cellulose as solvent) by gavage three times a day 1 h before CCl4 exposure, while other groups accepted vehicles of the equal volume. Fer-1 was prepared in DMSO (5 mg/kg), andi.p. injected into mice once 1 h before CCl4 exposure. The dosage of bicyclol was consistent with our previous work. The mice were then sacrificed to collect liver and serum samples after 24 or 48 h. REF000823 ICD-11: NB91 CCl4-induced iver injury CELL00304 L-02 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00792 Epigallocatechin-3-Gallate (EGCG) supplementation alleviated the liver oxidative damage caused by iron overload by inhibiting ferroptosis. EGCG addition increased NRF2 and GPX4 expression and elevated antioxidant capacity in iron overload mice. EGCG administration attenuates iron metabolism disorders by upregulating FTH/FTL expression. Through these two mechanisms, EGCG can effectively inhibit iron overload-induced ferroptosis. Suppressor . Up regulation . . Marker/Suppressor All mice were randomly divided into a 2 x 2 factorial arrangement, fed diets containing 40 mg/kg or 5000 mg/kg FeSO4 (the basis of the diet was AIN-93), and gavaged with PBS or 50 mg EGCG/kg body weight per day, respectively. The experiment lasted for 6 weeks, including a 1-week adaptation and a 3-week EGCG gavage; then, all mice were euthanized. REF001015 ICD-11: NB91 Liver Oxidative Damage CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00734 Kaempferol (KA) activated the Nrf2 pathway and upregulated Gpx4 in mouse livers and L02 cells to inhibit ferroptosis induced by APAP. Finally, molecular docking indicated the potential interaction of KA with Keap1. Taken together, KA ameliorated oxidative stress and ferroptosis-mediated acetaminophen-induced liver injury by activating Nrf2 signaling. Suppressor . Up regulation . . Marker/Suppressor Male BALB/c mice (8-week-old, 20-22 g) were purchased from Guangdong Medical Laboratory Animal Center (Guangzhou, China). The experimental animals were fed adaptively for one week in the Experimental Animal Center of Guangdong Pharmaceutical University (Guangzhou, China). Feeding conditions were set at 26 , humidity 65% and a lightdark cycle for 12 hours. All animal experiments were performed following the Guide for the Care and Use of Laboratory Animals, and the procedures were approved by the Research Ethical Committee of Guangdong Pharmaceutical University (gdpulacspf2020007). REF000958 ICD-11: NB91 Liver injury CELL00304 L-02 Ferroptosis (hsa04216) Cell ferroptosis
unique00338 Ulinastatin plays a role in mitigation of APAP-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression. Suppressor . Up regulation . . Marker/Suppressor Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection. REF000464 ICD-11: NB91 Liver injury CELL00304 LO2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00768 APAP could increase malondialdehyde (MDA) and Fe2+ levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced liver injury, NF-B activation and increased the expression of Nrf2 and HO-1. Suppressor . Up regulation . . Marker/Suppressor APAP-induced liver injury model was induced byintraperitoneal injection 300 mg/kg APAP. The mice of APAP + abietic acid (10, 20, 40 mg/kg) were given abietic acid by intraperitoneal injection 1 h before APAP treatment. The doses of abietic acid used in this study were based on previous studies. Twelve hours later, the mice were sacrificed after anesthesia with 1%pentobarbital (50 mg/kg) injected intraperitoneally and the samples were collected. REF000991 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL00541 AML12 Ferroptosis (hsa04216) Cell ferroptosis
unique01686 miR-129-3p affected ferroptosis under Se deficiency conditions through the SLC7A11 pathway. Our research provides a new perspective for the mechanism of Se deficiency on the liver damage. . . . Down regulation Driver Suppressor . REF000900 ICD-11: NB91 Liver injury CELL00032; CELL00032 Broiler Liver Tissue; LMH (chicken hepatoma cells) Ferroptosis (hsa04216) Cell ferroptosis
unique00250 DEHP disrupted the GSH metabolism via the xc/ GPX4 antioxidant system and, subsequently, caused the ferroptotic cell death, but Lycopene (Lyc) could effectively mitigate DEHP-induced damage to the antioxidant system. These findings indicated that Lyc may be an effective strategy for the prevention of DEHP-induced splenic toxicity via the regulation of ferroptosis. Suppressor . Up regulation . . Suppressor Three-week-old specific pathogen-free ICR (Institute of Cancer Research) male mice (weights of 18-22 g) were provided by Liaoning Changsheng Biotech Co. Ltd. The mice were housed under conditions at 22 ± 2 with 35-65% humidity and a light/dark cycle of 12 h/12 h in the cage. The animals were quarantined for a week before formal experiments, then randomly divided into seven groups: vehicle control group (Vcon), control group (Con), 5 mg/kg BW/d Lyc group (Lyc), 500 and 1000 mg/kg BW/d DEHP group (D5 and D10, respectively), DEHP + Lyc group (DL5 and DL10, respectively) (n = 20). The animals were exposed to DEHP via oral gavage, which lasted for 28 d, and then sacrificed after being anesthetized. REF000332 ICD-11: NB91 DEHP-induced splenic toxicity CELL10156 spleen cells Ferroptosis (hsa04216) Cell ferroptosis
unique01471 MSC-Exo protected against CCl4-induced acute liver injury (ALI) through inhibiting hepatocyte ferroptosis via restoring the SLC7A11 protein level. Additionally, the exosome-induced recovery of SLC7A11 protein was accompanied by upregulations of CD44 and OTUB1. . . . Up regulation Suppressor Suppressor ALI induction was performed in 6-8-week-old age-matched C57BL/6J male mice (n = 10-12 per group) by intraperitoneal injection of 3 mL/kg CCl4 in coconut oil. Control and negative control mice were injected with PBS and coconut oil, respectively. At 6 h after injection of CCl4, mice were divided into three groups: CCl4 group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + MSC group, injected with 5 x 105 MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + Fer-1 group, intraperitoneally injected with ferrostatin-1 (Fer-1, a ferroptosis inhibitor, 2.5 umol/kg body weight). Erastin, intraperitoneal injection of erastin (a ferroptosis inducer, 30 mg/kg body weight) twice every other day, and then the mice were divided into two groups (n = 10-12 per group): Erastin group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; Erastin + MSC group, injected with 5 x 105 MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through the tail vein. REF000701 ICD-11: NB91 Acute liver injury CELL10142 Primary hepatocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01472 MSC-Exo protected against CCl4-induced acute liver injury (ALI) through inhibiting hepatocyte ferroptosis via restoring the SLC7A11 protein level. Additionally, the exosome-induced recovery of SLC7A11 protein was accompanied by upregulations of CD44 and OTUB1. . . . Up regulation Suppressor Suppressor ALI induction was performed in 6-8-week-old age-matched C57BL/6J male mice (n = 10-12 per group) by intraperitoneal injection of 3 mL/kg CCl4 in coconut oil. Control and negative control mice were injected with PBS and coconut oil, respectively. At 6 h after injection of CCl4, mice were divided into three groups: CCl4 group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + MSC group, injected with 5 x 105 MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + Fer-1 group, intraperitoneally injected with ferrostatin-1 (Fer-1, a ferroptosis inhibitor, 2.5 umol/kg body weight). Erastin, intraperitoneal injection of erastin (a ferroptosis inducer, 30 mg/kg body weight) twice every other day, and then the mice were divided into two groups (n = 10-12 per group): Erastin group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; Erastin + MSC group, injected with 5 x 105 MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through the tail vein. REF000701 ICD-11: NB91 Acute liver injury CELL10142 Primary hepatocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00355 The relative amounts of CER and CL in the liver tissues of VBIT-12- or UAMC3203-treated APAP-injured mice markedly increased compared to those of APAP-injured mice. Smpd1 was the CER synthesis gene that was most significantly upregulated by UAMC3203 and VBIT-12. In summary, protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury. Suppressor Up regulation . . Suppressor . Male C57 BL /6J mice (6-8 weeks; 18-22 g each) were procured from the Experimental Animal Centre of Shanghai SLAC. All mice were fed in laboratory in vivo facilities with ad libitum food and water, within a temperature-/humidity-regulated environment (22 ± 1 ; Rh. = 65 ± 5%), adopting a 12-h circadian cycling process. Mice fasted overnight for 12 h and were randomly divided into different groups. REF000482 ICD-11: DB95.Z Acetaminophen-induced liver injury CELL10142 hepatocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00349 Microcystin-LR induces intestinal injury. Lesion morphological features (vacuolization, deformation and dilation of the endoplasmic reticulum [ER], absence of mitochondrial cristae in mid-intestine), up-regulated mRNA expressions of ER stress (eukaryotic translation initiation factor 2-alpha kinase 3, endoplasmic reticulum to nucleus signaling 1, activating transcription factor [ATF] 6, ATF4, DNA damage-inducible transcript 3), iron accumulation, and down-regulated activity of glutathione peroxidase (GPx) and glutathione (GSH) content were all typical characteristics of ferroptosis in intestinal tissue following MC-LR exposure. Inducer Up regulation . . Driver . In total, 90 common carp susceptible to MC-LR were obtained from Hulan Fishing Ground (Harbin, China) and acclimatized in 100 L glass aquaria (15 fish per tank) containing continuously aerated water at 23 under a 12 h light-dark cycle for 10 days prior to the experiments. Following acclimation, the fish in MC-LR treatment (M) group (45 fish in 3 tanks) were exposed to 10 ug/L of MC-LR for 15 days. The baseline mean body weights of the fish in the control (C) and M groups were 2.11 ± 0.03 and 2.12 ± 0.01 g, respectively. REF000475 ICD-11: NB91 Intestinal injury CELL10040 liver tissues; intestine tissues Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique00910 Treatment with erastin upregulated Sesn2 mRNA levels and luciferase reporter gene activity, and erastin-mediated Sesn2 induction was transcriptionally regulated by NF-E2-related factor 2 (Nrf2). Collectively, ferroptosis-mediated Sesn2 induction is dependent on Nrf2 and plays a protective role against iron overload and ferroptosis-induced liver injury. Suppressor Up regulation . . Suppressor . Six-weeks-old male ICR mice were obtained from Orient Bio (Sungnam, Korea) and acclimatized for 1 week. For Sesn2 overexpression, ICR mice were injected with the recombinant adenovirus particles (1 x 109 pfu) suspended in phosphate-buffered saline with tail vein. After 48 h, phenylhydrazine (PHZ, 60 mg/kg, i.p.) was administered to induce iron accumulation and liver injury. REF000078 ICD-11: NB91 Liver injury CELL00048; CELL00541; CELL10119 HepG2; AML-12; MEF Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00632 Inhibition of HSPA8 by rifampicin contributes to ferroptosis via enhancing autophagy. The present study highlights the crucial roles of the HSPA8 and autophagy in ferroptotic cell death driving by rifampicin, particularly illumines multiple promising regulatory nodes for therapeutic interventions in diseases involving anti-tuberculosis drug-induced liver injury (AT-DILI). Inducer Down regulation . . Suppressor . Male C57BL/6 mice (8-10 weeks old and weighing 20-25 g) were purchased from Hunan Experimental Animal Center (Changsha, China). All animals were housed in a 12/12h light/dark cycle and given free access to water and food. All experimental procedures were conducted in accordance with the institutional guidelines for animal care. After a minimum of 7 days of acclimation, the mice were randomly divided into five groups. DILI model group was given rifampicin (350 mg/kg) that was dissolved in saline by gavage daily for 14 days, and the same volume of saline was given as the control. Meanwhile, the other three groups were given the same volume of rifampicin to establish drug liver injury model, and treated with different compounds in the second week as follows: ferrostatin 1 (0.6 mg/kg) was injected into the tail vein every day after 2 h of rifampicin administration; geldanamycin (HSP90 inhibitor) (0.75 mg/kg) was intraperitoneally injected 2 h after rifampicin daily; 3-methyladenine (autophagy inhibitor) (15 mg/kg) was injected into tail vein 2 h after rifampicin every day. After 2 weeks of administration, serum was collected, and then mice were sacrificed by cervical dislocation. After that, liver tissue was taken for different treatments and used for reserve. REF000864 ICD-11: NB91 Anti-tuberculosis drug-induced liver injury CELL00048; CELL00541 HepG2; AML12 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01040 MiR-182-5p and miR-378a-3p induced ferroptosis in cells. And miR-182-5p and miR-378a-3p regulated the expression of GPX4 and SLC7A11 negatively by directly binding to the 3'UTR of GPX4 and SLC7A11 mRNA. In vivo study showed that silencing miR-182-5p and miR-378a-3p alleviated the I/R-induced kidney injury in rats. . . . Down regulation Driver Suppressor Male Sprague-Dawley (SD) rats (5 weeks old, weighting 180-220 g) were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. SD rats were anesthetized with an intraperitoneal (i.p.) injection of pentobarbital sodium (25 mg/kg) and placed on a surgical thermostator. Then the rats were subjected to an abdominal incision, and the right kidney was carefully liberated from surrounding tissue, and nephrectomy was performed. The left kidney was exposed after a midline incision, and the renal artery was clamped with non-traumatic clamps for 45 min, followed by restoring of the renal blood flow. The kidneys were harvested and the serum was collected 48 h after the surgery. The rats in sham group were subjected to an abdominal incision without clamping the renal artery. REF000255 ICD-11: NB92 Kidney injury CELL00093; CELL00556 HK-2; TCMK-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01039 MiR-182-5p and miR-378a-3p induced ferroptosis in cells. And miR-182-5p and miR-378a-3p regulated the expression of GPX4 and SLC7A11 negatively by directly binding to the 3'UTR of GPX4 and SLC7A11 mRNA. In vivo study showed that silencing miR-182-5p and miR-378a-3p alleviated the I/R-induced kidney injury in rats. . . . Down regulation Driver Suppressor Male Sprague-Dawley (SD) rats (5 weeks old, weighting 180-220 g) were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. SD rats were anesthetized with an intraperitoneal (i.p.) injection of pentobarbital sodium (25 mg/kg) and placed on a surgical thermostator. Then the rats were subjected to an abdominal incision, and the right kidney was carefully liberated from surrounding tissue, and nephrectomy was performed. The left kidney was exposed after a midline incision, and the renal artery was clamped with non-traumatic clamps for 45 min, followed by restoring of the renal blood flow. The kidneys were harvested and the serum was collected 48 h after the surgery. The rats in sham group were subjected to an abdominal incision without clamping the renal artery. REF000255 ICD-11: NB92 Kidney injury CELL00093; CELL00556 HK-2; TCMK-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00366 Cadmium activated the PERK-eIF2-ATF4-CHOP pathway and that inhibition of ER stress reduced ferroptosis caused by Cd. We further found that autophagy was required for Cd-induced ferroptosis because the inhibition of autophagy by chloroquine mitigated Cd-induced ferroptosis. Collectively, ferroptosis is involved in Cd-induced renal toxicity. Inducer Up regulation . . Driver . All specific pathogen free (SPF) grade Balb/c mice (6-8 weeks) were purchased from the Experimental Animal Center of Baiqiuem Medical College, Jilin University (China). The mice were reared under the conditions of 12 h of light and 12 h of darkness, supplemented with sufficient feed and free drinking water. The mice were treated according to a modified model as previous mentioned. In brief, a total of 15 mice were subjected to different doses of Cd (0, 2.5 and 5 mg/kg body weight/d) for 3 consecutive days intraperitoneally, and control mice were treated with 0.9% physiological saline. The concentrations of Cd were selected based on previous studies. At the day 4, the kidney tissue was collected and stored at -80 until detection. REF000499 ICD-11: NB92 CdCl2-induced renal toxicity CELL00556 TCMK-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01455 Atorvastatin suppressed the Nrf2, which would, in turn, inhibit the expression of System xc-(SLC7A11)and GPX4 (especially the mitochondrial GPX4), leading to a severe damage to the antioxidant system of ferroptosis.The datas point toward ferroptosis as an essential molecular mechanism leading to statin-induced muscle damage. Inducer . Down regulation . . Marker/Suppressor . REF000689 ICD-11: ND36 Muscle damage CELL10051; CELL00546; CELL10037 HCM; C2C12; HUVEC Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00559 Edaravone not only rescues the ferroptosis negative regulators, xCT and GPX4, but also downregulates those pro-ferroptosis factors, ACSL4 and 5-LOX. Therefore, secondary injury below the lesion site is reversed by edaravone via ferroptosis inhibition. And in the acute phase of spinal cord injury (SCI), edaravone reduced neuronal cell death and neuroinflammation. Suppressor . Down regulation . . Driver The rats were initially anesthetized with 5% isoflurane (RWD life science, Shenzhen, China) and then maintained with 22.5% isoflurane. A 1-cm midline incision was made over the thoracic vertebrae, and laminectomy on T10 and the caudal half of T9 vertebrae was performed. Spinal cord contusion injury was conducted by NYU Impactor Model III (W.M. Keck Center for Collaborative Neuroscience Rutgers, The State University of New Jersey, United States) using a 10-g node dropping freely from a height of 2.5 cm and muscles and skin sutured in layers. Sham controls underwent laminectomy without the contusion. To prevent infection at the incision, cefuroxime sodium was applied for 3 days after injury. The bladders were emptied manually twice daily in the first week after injury. REF000791 ICD-11: ND51 Spinal cord injury CELL10183 spinal cord tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01761 The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury. . . . Down regulation Suppressor Driver Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9). REF000987 ICD-11: ND51 Spinal cord injury CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01760 The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury. . . . Down regulation Suppressor Driver Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9). REF000987 ICD-11: ND51 Spinal cord injury CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
dupunique01760 The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury. . . . Up regulation Driver Driver Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9). REF000987 ICD-11: ND51 Spinal cord injury CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00560 Edaravone not only rescues the ferroptosis negative regulators, xCT and GPX4, but also downregulates those pro-ferroptosis factors, ACSL4 and 5-LOX. Therefore, secondary injury below the lesion site is reversed by edaravone via ferroptosis inhibition. And in the acute phase of spinal cord injury (SCI), edaravone reduced neuronal cell death and neuroinflammation. Suppressor . Down regulation . . Driver The rats were initially anesthetized with 5% isoflurane (RWD life science, Shenzhen, China) and then maintained with 22.5% isoflurane. A 1-cm midline incision was made over the thoracic vertebrae, and laminectomy on T10 and the caudal half of T9 vertebrae was performed. Spinal cord contusion injury was conducted by NYU Impactor Model III (W.M. Keck Center for Collaborative Neuroscience Rutgers, The State University of New Jersey, United States) using a 10-g node dropping freely from a height of 2.5 cm and muscles and skin sutured in layers. Sham controls underwent laminectomy without the contusion. To prevent infection at the incision, cefuroxime sodium was applied for 3 days after injury. The bladders were emptied manually twice daily in the first week after injury. REF000791 ICD-11: ND51 Spinal cord injury CELL10183 spinal cord tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01329 USP11 plays a key role in regulating ferroptosis and additionally identifies USP11-mediated autophagy-dependent ferroptosis as a promising target for the treatment of spinal cord ischemia-reperfusion injury (SCIRI). USP11 promotes autophagy activation by stabilizing Beclin 1, thereby leading to ferroptosis. . . . Up regulation Driver Driver The mouse SCIRI model was established in 6- to 8-week-old C57BL/6 male mice. Mice were anesthetized by isoflurane inhalation and fixed in a supine position, and a midline abdominal incision method was used. After positioning of the left kidney through the peritoneum, we carefully searched for and separated the abdominal aorta along the left renal artery. The abdominal aorta was clamped under the exit of the left renal artery (which was not clamped in sham-operated mice). After 60 min, the aneurysm clip was removed and blood perfusion was restored. After the operation, the mice were placed in a cage alone and kept warm, and the bladder was massaged once every 8 h until the bladder reflex was restored. REF000594 ICD-11: ND51 Spinal cord injury CELL00057 HEK 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00558 Edaravone not only rescues the ferroptosis negative regulators, xCT and GPX4, but also downregulates those pro-ferroptosis factors, ACSL4 and 5-LOX. Therefore, secondary injury below the lesion site is reversed by edaravone via ferroptosis inhibition. And in the acute phase of spinal cord injury (SCI), edaravone reduced neuronal cell death and neuroinflammation. Suppressor . Up regulation . . Suppressor The rats were initially anesthetized with 5% isoflurane (RWD life science, Shenzhen, China) and then maintained with 22.5% isoflurane. A 1-cm midline incision was made over the thoracic vertebrae, and laminectomy on T10 and the caudal half of T9 vertebrae was performed. Spinal cord contusion injury was conducted by NYU Impactor Model III (W.M. Keck Center for Collaborative Neuroscience Rutgers, The State University of New Jersey, United States) using a 10-g node dropping freely from a height of 2.5 cm and muscles and skin sutured in layers. Sham controls underwent laminectomy without the contusion. To prevent infection at the incision, cefuroxime sodium was applied for 3 days after injury. The bladders were emptied manually twice daily in the first week after injury. REF000791 ICD-11: ND51 Spinal cord injury CELL10183 spinal cord tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01809 In spinal cord injury (SCI) rats, USP7 directly bound to HMOX-1 and its overexpression promoted HMOX-1 expression via deubiquitination. To sum up, USP7 overexpression facilitated the expression of HMOX-1 through deubiquitination, thereby reducing ferroptosis and alleviating SCI. . . . Up regulation Suppressor Driver/Suppressor Forty-eight adult female Sprague-Dawley rats weighing 200-220 g were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Hunan, China) and divided into the following eight groups: sham (n = 6), SCI (n = 6), SCI + lentivirus (LV)-negative control 1 (NC1) (n = 6), SCI + LV-HMOX-1 (n = 6), SCI + LV-NC2 (n = 6), SCI + LV-USP7 (n = 6), SCI + LV-USP7 + sh-NC (n = 6), and SCI + LV-USP7 + sh-HMOX-1 (n = 6) groups. One week after animal adaptation and 30 min before operation, a subcutaneous injection of buprenorphine (0.05 mg/kg) was administered to the rats, along with inhalation of 5% isoflurane and an intraperitoneal injection of ketamine (75 mg/kg) and thiazide (10 mg/kg). REF001040 ICD-11: ND51 Spinal cord injury CELL10184 Spinal cord Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01581 GDF15 effectively alleviated neuronal ferroptosis post spinal cord injury (SCI) via the p62-Keap1-Nrf2 signaling pathway and promoted locomotor recovery of SCI mice, which is suggested as a potential target on SCI pathogenesis and treatment. . . . Up regulation Suppressor Marker/Suppressor Total of 50 C57BL/6J adult mice (males, average weight of 20 g, 8 weeks of age) were acquired from Charles River (Beijing, China). In brief, ketamine (80 mg/kg) was utilized to anesthetize mice before the skin was prepared for disinfection, and then the back skin was incised to expose the lamina at T10. Finally, a moderate contusion (5 g x 5 cm) was created by an impactor (RWD, Shenzhen, China). Spinal cord hemorrhage, hindlimb extension, and delayed paralysis suggest successful modeling. Only laminectomy was performed in the Sham group. REF000785 ICD-11: ND51 Spinal cord injury CELL10181 Primary Neurons Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00223 Ferroptosis is involved in the pathogenesis of spinal cord injury (SCI). Carnosic acid (CA) is a natural phenolic diterpene, which possesses diversiform activities. CA can inhibit ferroptosis in PC12 cells induced by erastin via activating Nrf2 pathway, indicating that CA could lead to neuroprotective effect by restraining the occurrence of ferroptosis. Suppressor . Up regulation . . Marker/Suppressor . REF000285 ICD-11: ND51 Spinal cord injury CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01433 miR-672-3p exerts a neural restoration effectin vivo and in vitro by inhibiting ferroptosis via the FSP1 pathway. In addition, miR-672-3p improved locomotor function in spinal cord injury rats, suggesting its potential as a target for the development of therapeutics for SCI. . . . Down regulation Driver Suppressor Adult male Sprague-Dawley rats weighing 200-220 g were purchased from the Animal Center of the Medical Department of Xi'an Jiaotong University. The rats were anesthetized by intraperitoneal injection of 1% pentobarbital sodium (50 mg/kg), and the spines of the rats were fixed. The skin of T9-12 level was incised, and laminectomy was performed at the T10 level to expose the spinal cord. The rats were then placed in the appropriate position of the impactor so that 10 g of rod fell freely at a height of 3 cm and hit the center of the T10 level of the spinal cord. The signs of successful establishment of the model were the appearance of hind limb extension and tail-flick reflex in rats. Laminectomy was performed only in the sham-operated group. The rats in the SCI group received an artificial bladder massage twice a day to assist in urination until they were able to urinate. REF000674 ICD-11: ND51 Spinal cord injury CELL00321; CELL00597 AGE1.HN; PC12 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01440 Exosomes derived from mesenchymal stem cells (MSCs) have been considered as an alternative for cell therapy of acute spinal cord injury (ASCI). MSCs-exosomes lncGm36569 inhibited neuronal cell ferroptosis through miR-5627-5p/FSP1 axis, thereby attenuating neuronal dysfunction. . . . Up regulation Suppressor Suppressor Male C57BL/6 (7-8 weeks) were purchased from the Animal Center of Nanjing University (Nanjing, China) and housed in the condition with controlled temperature and humidity under a 12-h light/dark circadian rhythm. For determining the effects of MSCs-exo, the animals were derived into three groups: sham (n = 10), ASCI (n = 10), ASCI + MSCs (n = 10); for determining the effects of exosomal lncGm36569, the animals were divided into five groups: sham (n = 10), ASCI (n = 10), ASCI + MSC-Exo (ctrl) (n = 10), ASCI + MSCs-Exo (lnc-OE) (n =10), ASCI + MSCs-Exo (si-lnc) (n = 10). REF000680 ICD-11: ND51 Acute spinal cord injury CELL00549; CELL00057 HT-22; HEK-293 T Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01441 Exosomes derived from mesenchymal stem cells (MSCs) have been considered as an alternative for cell therapy of acute spinal cord injury (ASCI). MSCs-exosomes lncGm36569 inhibited neuronal cell ferroptosis through miR-5627-5p/FSP1 axis, thereby attenuating neuronal dysfunction. . . . Down regulation Driver Suppressor Male C57BL/6 (7-8 weeks) were purchased from the Animal Center of Nanjing University (Nanjing, China) and housed in the condition with controlled temperature and humidity under a 12-h light/dark circadian rhythm. For determining the effects of MSCs-exo, the animals were derived into three groups: sham (n = 10), ASCI (n = 10), ASCI + MSCs (n = 10); for determining the effects of exosomal lncGm36569, the animals were divided into five groups: sham (n = 10), ASCI (n = 10), ASCI + MSC-Exo (ctrl) (n = 10), ASCI + MSCs-Exo (lnc-OE) (n =10), ASCI + MSCs-Exo (si-lnc) (n = 10). REF000680 ICD-11: ND51 Acute spinal cord injury CELL00549; CELL00057 HT-22; HEK-293 T Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00224 (-)-Epigallocatechin-3-gallate (EGCG) upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST. Together, EGCG is a novel strategy for the treatment of spinal cord injury (SCI) related to PKD1 phosphorylation and ferroptosis. Suppressor Up regulation . . Suppressor . . REF000286 ICD-11: ND51 Spinal cord injury CELL10168 CGNs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00685 Astragaloside IV markedly accelerated proliferation, suppressed apoptosis, and reduced ROS and LDH accumulation. Furthermore, AS-IV enhanced TFEB expression in H2O2-damaged PC12 cells. The effects of AS-IV on spinal cord injury were inhibited by si-TFEB, and this inhibition was further reinforced by the addition of FIN56.The results of this investigation using the SCI cell model suggested that AS-IV alleviated SCI by promoting TFEB expression and subsequently mediating ferroptosis. Inducer Up regulation . . Driver . . REF000910 ICD-11: ND51 Spinal cord injury CELL00597 PC12 Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00395 Nicotinamide mononucleotide recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation-induced skin injury and inhibits oxidative skin damage. NMN or ferroptosis inhibitor might become promising therapeutic approaches for treating oxidative stress-induced Skin injury. Suppressor . Up regulation . . Suppressor The skin injury model was created using ultraviolet B (UVB) 250 mJ/cm2 irradiation onto BALB/c mice after their back shaved. A total of 26 mice were used in this study; 8 mice without treatment served as controls, while 18 mice were irradiated under the UVB lamp and administered with PBS (200 ul per injection area), Lip-1 (Selleck, S7699) (10 mg/kg every other day per injection area), or NMN (Chalet Healthy PTY Ltd, Jiangsu Chengxin Pharmaceutical Co., Ltd) (400 mg/kg/day via drinking water at pH 7.2). REF000534 ICD-11: ND56 Skin injury CELL00053 HaCaT Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00214 Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity. Inducer . Up regulation . . Driver Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo. REF000273 ICD-11: NE61 Formaldehyde-induced neurotoxicity CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00213 Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity. Inducer . Up regulation . . Marker Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo. REF000273 ICD-11: NE61 Formaldehyde-induced neurotoxicity CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00215 Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity. Inducer . Up regulation . . Driver Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo. REF000273 ICD-11: NE61 Formaldehyde-induced neurotoxicity CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00216 Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity. Inducer . Up regulation . . Driver Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo. REF000273 ICD-11: NE61 Formaldehyde-induced neurotoxicity CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01741 Sevoflurane could enhance 15LO2-PEBP1 interaction and activate ATM and its downstream P53/SAT1 pathway, which might be attributed to excessive p-ATM nuclear translocation, indicating a potential therapeutic target for ameliorating sevoflurane-induced neurotoxicity. Inducer Up regulation . . Driver . Pregnant rats were placed in a dedicated plastic chamber with ambient gas at a flow rate of 2L/min. Fer-1 solubilized in saline and 1% dimethyl sulfoxide (DMSO) and PD146176 (a specific 15LOX inhibitor) dissolved in corn oil containing 1% DMSO were administered intraperitoneally to rats at a dose of 5 mg/kg 1 h before each exposure, respectively. Similarly, 0.5 mg/kg Ku55933 (an ATM inhibitor), which is diluted in saline containing 1% DMSO, was intraperitoneally administered 2 h previously. REF000960 ICD-11: NE61 Sevoflurane induced neurotoxicity CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00832 Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). . . . Up regulation Suppressor Marker/Suppressor . REF000016 ICD-11: PK81 Bone marrow injury CELL10111 Bone marrow Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00833 Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). . . . Down regulation Suppressor Marker/Suppressor . REF000016 ICD-11: PK81 Bone marrow injury CELL10111 Bone marrow Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00834 Bone marrow injury remains a serious concern in traditional cancer treatment. FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). . . . Down regulation Suppressor Marker/Suppressor/Driver . REF000016 ICD-11: PK81 Bone marrow injury CELL10111 Bone marrow Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01363 The mTOR kinase can be assembled into two structurally and functionally distinct complexes, mTORC1 and mTORC2, both of which share the same catalytic subunit mTOR but differ in two scaffold subunits, Raptor for mTORC1 and Rictor for mTORC2, respectively. mTORC2 inactivation resulted in the impaired phosphorylation of downstream AKT and GSK3B kinases, which induced aberrant mitochondrial reactive oxygen species (ROS) accumulation and ensuing ferroptosis-causative lipid peroxidation in virus-specific memory CD4T cells; furthermore, the disruption of this signaling cascade also inhibited glutathione peroxidase 4 (GPX4) in thymoma cells. . . . Up regulation Suppressor Suppressor A total of 1 x 106 naive SMARTA (CD45.1) cells were adoptively transferred into naive WT congenic recipient mice (CD45.2). On the following day, the recipients were intraperitoneally infected with 1 x 10++6PFU of LCMV Arm. BM cells were collected from WT C57BL/6J mice and KO mice. REF000622 ICD-11: 2C27 Thymoma CELL10110; CELL00547 BMCs; EL4 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01037 Palmitic acid (PA) decreased the protein expression levels of both heat shock factor 1 (HSF1) and glutathione peroxidase 4 (GPX4) in a dose- and time-dependent manner, which were restored by different ferroptosis inhibitors. Altogether, HSF1 may function as a key defender against PA-induced ferroptosis in cardiomyocytes by maintaining cellular iron homeostasis and GPX4 expression. Inducer Down regulation Down regulation Up regulation Suppressor Suppressor Hsf1 and Hsf1+/+-/- mice were kindly given as a present by Dr. Ivor J. Benjamin (Froedtert & Medical College of Wisconsin, Milwaukee, WI, USA). Sex-matched Hsf1-/- mice and Hsf1 littermates were used at 16-20 weeks old. Each mouse was injected intraperitoneally with 2.5 umol PA (dissolved in 0.5 mL 10% BSA) or an equal volume of BSA twice daily for 7 days. REF000252 ICD-11: N.A. Health CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00917 Following addition of the JNK (MAPK8) inhibitor SP600125, the expression of HO-1 decreased, expression of FTH1 was increased and iron accumulation was decreased. Therefore, it was hypothesized that NPs induced ferroptosis in BV2 cells via the JNK/HO-1/FTH1 pathway. Suppressor Down regulation Down regulation Up regulation Driver Driver/Suppressor . REF001041 ICD-11: N.A. Health CELL00544 BV2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00429 This study confirmed the protective effect of calcitriol on RSL3-induced ferroptosis in zebrafish liver cells, and reported for the first time that calcitriol inhibits ferroptosis in fish cells by regulating the Keap1/Nrf2/GPx4 axis and NF-kB/hepcidin axis. Suppressor Down regulation Up regulation Down regulation Driver Marker/Suppressor . REF000578 ICD-11: N.A. Health CELL00031 ZFL Ferroptosis (hsa04216); Pathways in cancer (hsa05200); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique01176 HHV7 infection increases the concentrations of the ROS, increasing oxidative stress via the activation of Cox4i2. On the one hand, Cox4i2 facilitates the intracellular iron overload and redox imbalance and induces ferroptosis. On the other hand, the upregulation of oxidative stress induced by Cox4i2 activates caspase3 by regulating the ERK signalling pathway and promotes apoptosis. . . . . Driver . Twenty three-weeks-old female Wistar rats weighing 60-80 g were randomly divided into control and experimental groups after adaptive feeding for 7 days. The rats were treated by scratching the unilateral auricular surface with needle 27 after 3% halothane anaesthesia. The scratching side of auricular surface was inoculated with 0.1 mL HHV7 virus solution [titer of 1.0 x 106 plaque-forming units (PFU) per mL] in the experimental group, whereas PBS was used in the control group. REF000414 ICD-11: 1C80 HHV7 infection CELL00604 RSC96 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01248 Inhibiting FADS2 markedly enhances hepatitis C virus (HCV) replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Collectively, these data establish FADS2 as an important pro-ferroptotic factor that also restricts HCV replication. . . . . Driver . Chimeric mice were purchased from PhoenixBio Co. (Hiroshima, Japan). The chimeric mice were generated by transplanting human primary hepatocytes into severe combined immunodeficient mice (3-week-old male) carrying the urokinase plasminogen activator transgene under control of an albumin promoter (Alb-uPA). REF000497 ICD-11: 1E51 Hepatitis C CELL00488; CELL00484; CELL00536; CELL00045 Huh-7.5; 293FT; PH5CH8; A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01407 EPCs-Exos inhibited Erastin-induced HUVEC ferroptosis and endothelial injury. EPCs-Exos promoted the activation of the AMPK pathway by upregulating the expression of miR-30e-5p in HUVECs and inhibiting the expression of SP1 in HUVECs, thus inhibiting Erastin-induced cell ferroptosis. . . . . Suppressor . . REF000651 ICD-11: 1F00 Endotheliitis CELL10011; CELL10037 Endothelial progenitor cells (EPCs); HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis
unique01408 EPCs-Exos inhibited Erastin-induced HUVEC ferroptosis and endothelial injury. EPCs-Exos promoted the activation of the AMPK pathway by upregulating the expression of miR-30e-5p in HUVECs and inhibiting the expression of SP1 in HUVECs, thus inhibiting Erastin-induced cell ferroptosis. . . . . Driver . . REF000651 ICD-11: 1F00 Endotheliitis CELL10011; CELL10037 Endothelial progenitor cells (EPCs); HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis
unique01535 3 FRDEGs ( TLR4, WIPI1, and GABARAPL2), with high sensitivity and specificity in sepsis diagnosis, were selected for construction of prognostic risk signature. The expression of genes in risk signature was also validated in CLP mouse model via qRT-PCR. . . . . Driver . Beijing Vital River Laboratory Animal Technology Co. Ltd. provided 20 specific pathogen-free female C57BL/6J mice (8-10 weeks old, weighing 20-22g). All procedures on mice were performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering. 12 h after surgery, the blood was collected from orbital sinus. REF000753 ICD-11: 1G40-1G41 Sepsis . . Ferroptosis (hsa04216) Cell ferroptosis
unique01534 3 FRDEGs (TLR4, WIPI1, and GABARAPL2), with high sensitivity and specificity in sepsis diagnosis, were selected for construction of prognostic risk signature. The expression of genes in risk signature was also validated in CLP mouse model via qRT-PCR. . . . . Driver . Beijing Vital River Laboratory Animal Technology Co. Ltd. provided 20 specific pathogen-free female C57BL/6J mice (8-10 weeks old, weighing 20-22g). All procedures on mice were performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering. 12 h after surgery, the blood was collected from orbital sinus. REF000753 ICD-11: 1G40-1G41 Sepsis . . Ferroptosis (hsa04216) Cell ferroptosis
unique01536 3 FRDEGs (TLR4, WIPI1, and GABARAPL2), with high sensitivity and specificity in sepsis diagnosis, were selected for construction of prognostic risk signature. The expression of genes in risk signature was also validated in CLP mouse model via qRT-PCR. . . . . Driver . Beijing Vital River Laboratory Animal Technology Co. Ltd. provided 20 specific pathogen-free female C57BL/6J mice (8-10 weeks old, weighing 20-22g). All procedures on mice were performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering. 12 h after surgery, the blood was collected from orbital sinus. REF000753 ICD-11: 1G40-1G41 Sepsis . . Ferroptosis (hsa04216) Cell ferroptosis
unique01732 Overexpression of TFR2 promoted the production of reactive oxygen species and lipid peroxidation in glioma cells, thereby further promoting ferroptosis. In conclusion, TFR2 induced ferroptosis and enhanced TMZ sensitivity in gliomas. . . . . . Driver . REF000953 ICD-11: 2A00 Glioma CELL00043; CELL00295 U251; U87 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01799 CYBB captured ferroptosis resilience in mesenchymal glioblastoma multiforme (GBM). The downstream compensatory activity of CYBB via the Nrf2/SOD2 axis is exploitable through erastin-induced ferroptosis to overcome TMZ resistance. . . . . . Suppressor A total of four groups were formed by randomly dividing the mice: control group consisting of shScramble xenografts treated with vehicle (n = 5), shScramble xenografts treated with IKE (n = 5), shSOD2 xenografts treated with vehicle (n = 5), and shSOD2 xenografts treated with IKE (n = 5). Drug treatment was started after the tumor volume reached approximately 100 mm3 or 10 days after the injection of the tumor xenograft. Depending on the treatment group, vehicles (5 mg/kg/day) or IKE (25 mg/kg/day) were administered intraperitoneally. Treatment was administered intraperitoneally for 3 weeks, and tumor growth was observed for 6 weeks after treatment began. REF001029 ICD-11: 2A00 Glioblastoma CELL00323 U87MG Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00159 Doranidazole and misonidazole, but not metronidazole, manifested radiation-independent cytotoxicity for hypoxic glioma stem cells (GSCs) that was mediated by ferroptosis induced partially through blockade of mitochondrial complexes I and II and resultant metabolic alterations in oxidative stress responses. Inducer . . . . . Female C57BL/6J mice (age 6-8 weeks) were anesthetized and placed into a stereotactic apparatus (David Kopf Instruments, Tujunga, CA). One thousand viable GSC-H cells were injected into the right hemisphere at a position 2 mm lateral to the bregma and 3 mm below the brain surface. After 10 days, animals were exposed to 15 Gy (radiation dose rate, 1.45 Gy/min) with or without prior injection of doranidazole (200 mg/kg, i.p.). Radiation was confined to the brain by protection of the body with a lead shield. REF000212 ICD-11: 2A00 Glioma CELL10121; CELL10122 GICs; GSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00401 FIN56 decreased cell viability, inhibited cell proliferation and caused cell cycle arrest on gliomaLN229 and U118 cells. Further study showed that FIN56 induced ferroptosis and induced lysosomal membrane permeabilization in a ferroptosis and transfactor EB dependent manner. Animal study demonstrated that FIN56 inhibited glioma growth and caused ferroptosisin vivo. Inducer . . . . . 1x105 LN229 cells were injected subcutaneously into the right shoulder of 4-week-old nude mice (SLAC laboratory animal Center; Shanghai, China). 2 weeks later, nude mice (n = 10) were divided into two groups, control group and FIN56 treatment group. Subcutaneous tumors were harvested 30 days after treatment. Tumors were fixed and paraffin-embedded for immunohistochemistry. REF000547 ICD-11: 2A00 Glioma CELL00107; CELL00351 LN229; U118 Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique01832 Amplifying IRP1 signals can reverse TMZ resistance and suppress tumor growthin vivo via inhibiting NFKB2 in the noncanonical NF-B signaling pathway. In addition, NFKB2 affected TMZ sensitivity of glioblastoma by modulating the expression of LCN2 and FPN1 in glioblastoma. . . . . Suppressor . Four-to five-week-old female BALB/c nude mice were obtained from the Laboratory Animal Center, Southern Medical University. To study the role of IRP1 in TMZ resistance, the mice were randomly divided into four groups (n = 6 per group) (U87TR, U87TR + TMZ, U87TR-lvIRP1, U87TR-lvIRP1 + TMZ). To establish the GBM models, IRP1 overexpress or control U87TR cells (5 x 105 cells per mice in 3 uL PBS) transfected with luciferase lentivirus were injected into the mice brain under the guidance of a stereotactic instrument at coordinates relative to bregma: 2.0 mm posterior, 2.0 mm lateral, and 3.0 mm ventral. REF001054 ICD-11: 2A00 Glioblastoma CELL00579; CELL00578; CELL00506; CELL00295; CELL00043; CELL00107; CELL00068; CELL00351 N9; N33; NHA; T98; U87; U251; LN229; A172; U118 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique00158 Doranidazole and misonidazole, but not metronidazole, manifested radiation-independent cytotoxicity for hypoxic glioma stem cells (GSCs) that was mediated by ferroptosis induced partially through blockade of mitochondrial complexes I and II and resultant metabolic alterations in oxidative stress responses. Inducer . . . . . Female C57BL/6J mice (age 6-8 weeks) were anesthetized and placed into a stereotactic apparatus (David Kopf Instruments, Tujunga, CA). One thousand viable GSC-H cells were injected into the right hemisphere at a position 2 mm lateral to the bregma and 3 mm below the brain surface. After 10 days, animals were exposed to 15 Gy (radiation dose rate, 1.45 Gy/min) with or without prior injection of doranidazole (200 mg/kg, i.p.). Radiation was confined to the brain by protection of the body with a lead shield. REF000212 ICD-11: 2A00 Glioma CELL10121; CELL10122 GICs; GSCs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01305 Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of U87 cells and U251 cells. These findings were expected to provide promising therapeutic targets for the treatment of glioma. . . . . Suppressor . In this study, 4-week-old specific pathogen free male nude mice were selected and assigned into 4 groups, each of which was respectively injected with U251 cells and U87 cells transfected with NC, hsa-miR-27a-3p angomir, si-TMEM161B-AS1, si-TMEM161B-AS1 + hsa-miR-27a-3p angomir. Each nude mouse was subcutaneously injected with 4 x 105 cells in the right flank area for subcutaneous implantation. REF000558 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01307 Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of glioma U87 cells and U251 cells. These findings were expected to provide promising therapeutic targets for the treatment of glioma. . . . . Suppressor . In this study, 4-week-old specific pathogen free male nude mice were selected and assigned into 4 groups, each of which was respectively injected with U251 cells and U87 cells transfected with NC, hsa-miR-27a-3p angomir, si-TMEM161B-AS1, si-TMEM161B-AS1 + hsa-miR-27a-3p angomir. Each nude mouse was subcutaneously injected with 4 x 105 cells in the right flank area for subcutaneous implantation. REF000558 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01308 Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of U87 cells and U251 cells. These findings were expected to provide promising therapeutic targets for the treatment of glioma. . . . . Suppressor . In this study, 4-week-old specific pathogen free male nude mice were selected and assigned into 4 groups, each of which was respectively injected with U251 cells and U87 cells transfected with NC, hsa-miR-27a-3p angomir, si-TMEM161B-AS1, si-TMEM161B-AS1 + hsa-miR-27a-3p angomir. Each nude mouse was subcutaneously injected with 4 x 105 cells in the right flank area for subcutaneous implantation. REF000558 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01306 Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of U87 cells and U251 cells. These findings were expected to provide promising therapeutic targets for the treatment of glioma. . . . . Driver . In this study, 4-week-old specific pathogen free male nude mice were selected and assigned into 4 groups, each of which was respectively injected with U251 cells and U87 cells transfected with NC, hsa-miR-27a-3p angomir, si-TMEM161B-AS1, si-TMEM161B-AS1 + hsa-miR-27a-3p angomir. Each nude mouse was subcutaneously injected with 4 x 105 cells in the right flank area for subcutaneous implantation. REF000558 ICD-11: 2A00 Glioma CELL00295; CELL00043 U87; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique00967 Levels of circ-TTBK2 and ITGB8 were upregulated, whereas miR-761 level was low-expressed in glioma tissues and cells. Circ-TTBK2 was a sponge of miR-761 to modulate ITGB8. Additionally, circ-TTBK2 knockdown or miR-761 increase could retard cell proliferation, invasion, and promote ferroptosis in glioma cells. . . . . Suppressor . The stably transfected LN229 cells were set up via the lentivirus-mediation of sh-circ-TTBK2 or sh-NC. Then, the stably transfected LN229 cells (2 x 106 ) were injected into the Balb/c nude mice (4 weeks old, n = 6/group) subcutaneously, which were purchased from Vital River Laboratory Animal Technology (Beijing, China). REF000152 ICD-11: 2A00 Glioma CELL00107; CELL00043 LN229; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique00969 Levels of circ-TTBK2 and ITGB8 were upregulated, whereas miR-761 level was low-expressed in glioma tissues and cells. Circ-TTBK2 was a sponge of miR-761 to modulate ITGB8. Additionally, circ-TTBK2 knockdown or miR-761 increase could retard cell proliferation, invasion, and promote ferroptosis in glioma cells. . . . . Suppressor . The stably transfected LN229 cells were set up via the lentivirus-mediation of sh-circ-TTBK2 or sh-NC. Then, the stably transfected LN229 cells (2 x 106 ) were injected into the Balb/c nude mice (4 weeks old, n = 6/group) subcutaneously, which were purchased from Vital River Laboratory Animal Technology (Beijing, China). REF000152 ICD-11: 2A00 Glioma CELL00107; CELL00043 LN229; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique00968 Levels of circ-TTBK2 and ITGB8 were upregulated, whereas miR-761 level was low-expressed in glioma tissues and cells. Circ-TTBK2 was a sponge of miR-761 to modulate ITGB8. Additionally, circ-TTBK2 knockdown or miR-761 increase could retard cell proliferation, invasion, and promote ferroptosis in glioma cells. . . . . Driver . The stably transfected LN229 cells were set up via the lentivirus-mediation of sh-circ-TTBK2 or sh-NC. Then, the stably transfected LN229 cells (2 x 106 ) were injected into the Balb/c nude mice (4 weeks old, n = 6/group) subcutaneously, which were purchased from Vital River Laboratory Animal Technology (Beijing, China). REF000152 ICD-11: 2A00 Glioma CELL00107; CELL00043 LN229; U251 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique01563 NRF2 positively correlates with ABCC1 expression in tumor tissues of glioma patients, which can be associated with tumor aggressiveness, drug resistance, and poor overall survival. . . . . Driver . . REF000774 ICD-11: 2A00 Glioma CELL00043; CELL00137 U251MG; T98G Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique00212 The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in CCRF-CEM cellsviacaspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis in glioblastoma. Inducer . . . . . . REF000272 ICD-11: 2A00 Glioblastoma CELL00541; CELL00323 AML-12; U87MG Apoptosis (hsa04210); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01168 MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low E-cadherin create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma. . . . . Suppressor . 6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable. REF000405 ICD-11: 2A01 Meningiomas CELL00464; CELL00465; CELL10081 CH157-MN; IOMM-Lee; PM3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01169 MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma. . . . . Suppressor . 6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable. REF000405 ICD-11: 2A01 Meningiomas CELL00464; CELL00465; CELL10081 CH157-MN; IOMM-Lee; PM3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01170 MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma. . . . . Suppressor . 6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable. REF000405 ICD-11: 2A01 Meningiomas CELL00464; CELL00465; CELL10081 CH157-MN; IOMM-Lee; PM3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00460 TXNRD1 is a key regulator involved in the ferroptosis of chronic myeloid leukemia cells induced by cysteine depletion in vitro. These findings highlight that cysteine depletion serves as a potential therapeutic strategy for overcoming chemotherapy resistance CML. . . . . Suppressor . . REF000611 ICD-11: 2A20 Chronic myeloid leukemia CELL00036; CELL00450 K562; K562/G01 Fatty acid metabolism (hsa01212); Glutathione metabolism (hsa00480) Cell ferroptosis
unique01604 ARNTL expression is closely associated with tumor-infiltrating immune cells like the macrophages and NK cells. Inhibiting the ARNTL expression suppressed colony formation and induced ferroptosis in acute myeloid leukemia (AML) cells. . . . . Suppressor . . REF000811 ICD-11: 2A60 Acute myeloid leukemia CELL00239 Molm-13 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01127 The overexpression of circKDM4C in AML cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to acute myeloid leukemia (AML) patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. . . . . Driver . All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured. REF000361 ICD-11: 2A60 Acute myeloid leukemia CELL10003; CELL00036; CELL00038; CELL00035; CELL00239 BMSCs; K-562; THP-1; HL-60; MOLM-13 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01128 The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. . . . . Suppressor . All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured. REF000361 ICD-11: 2A60 Acute myeloid leukemia CELL10003; CELL00036; CELL00038; CELL00035; CELL00239 BMSCs; K-562; THP-1; HL-60; MOLM-13 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
dupunique01127 The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. . . . . Driver . All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 106, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured. REF000361 ICD-11: 2A60 Acute myeloid leukemia CELL10003; CELL00036; CELL00038; CELL00035; CELL00239 BMSCs; K-562; THP-1; HL-60; MOLM-13 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00196 T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest multiple myeloma cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis. Inducer . . . . . . REF000259 ICD-11: 2A83.1 Multiple myeloma CELL00240; CELL00206; CELL00001; CELL00364; CELL00423; CELL00188; CELL00238; CELL00394; CELL00209; CELL00206 MOLP-8; NCI-H929; RPMI-8226; KMS-12BM; KMS-11; L-363; JJN-3; AMO-I; OPM-2; NCI-H929 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique00518 Poricoic acid A could significantly inhibit T-cell acute lymphoblastic leukemia (T-ALL) progression by inducing G2/M phase, apoptosis, mitochondrial dysfunction, ROS generation, autophagy and ferroptosis without detectable side effects both in vitro and in vivo. Inducer . . . . . BALB/c Nude Mice (4-6 weeks old) were purchased from Shanghai Experimental Animal Center of the Chinese Academy of Sciences (Shanghai, China) and then subcutaneously injection with JURKAT cells (1 x 107) suspended in 100 uL PBS. Tumor volume was measured once a week with a caliper according to the formula: 1/2 x length x width2. After tumors reached 100-200 mm3(at day 4), the mice were randomly assigned to three groups: the Control group, low dose of PAA (5 mg/kg) and high dose of PAA (10 mg/kg). PAA was administered through i.p. injection once a day at 5 or 10 mg/kg body weight. Mice in normal control group were given equal amounts of vehicle (saline). Body weights of mice were measured once a week during PAA treatments. After 4 weeks, blood samples were collected from each group of mice, and tumor tissues were removed and weighed for further analysis. REF000708 ICD-11: 2A90 T-cell acute lymphoblastic leukemia CELL00059; CELL00146; CELL00390; CELL00553; CELL00093; CELL00319; CELL00304 JURKAT; MOLT-3; ALL-SIL ADN RPMI-8402; RAW264.7; HK2; CAM191; L02 Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique01375 Circ_0000745 promoted cell cycle progression and glycolytic metabolism and inhibited the apoptosis and ferroptosis of acute lymphoblastic leukemia cells by regulating miR-494-3p/NET1 axis. Circ_0000745/miR-494-3p/NET1 axis may provide novel potential targets for the diagnosis and treatment of acute lymphoblastic leukemia (ALL). . . . . Suppressor . . REF000626 ICD-11: 2B33 Acute lymphoblastic leukemia CELL00020; CELL00105 Kasumi-1; KG-1; primary T cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Gluconeogenesis (hsa00010); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00195 T. vulgaris and A. lappa could be considered as potential herbal drug candidates, which arrest leukemia cancer cell proliferation by induction of apoptosis, autophagic, and ferroptosis. Inducer . . . . . . REF000259 ICD-11: 2B33 Myeloid leukaemia CELL00080; CELL00206 CCRF-CEM; NCI-H929 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique01374 Circ_0000745 promoted cell cycle progression and glycolytic metabolism and inhibited the apoptosis and ferroptosis of acute lymphoblastic leukemia cells by regulating miR-494-3p/NET1 axis. Circ_0000745/ miR-494-3p/NET1 axis may provide novel potential targets for the diagnosis and treatment of acute lymphoblastic leukemia (ALL). . . . . Driver . . REF000626 ICD-11: 2B33 Acute lymphoblastic leukemia CELL00020; CELL00105 Kasumi-1; KG-1; primary T cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Gluconeogenesis (hsa00010); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique01376 Circ_0000745 promoted cell cycle progression and glycolytic metabolism and inhibited the apoptosis and ferroptosis of acute lymphoblastic leukemia cells by regulating miR-494-3p/ NET1 axis. Circ_0000745/miR-494-3p/ NET1 axis may provide novel potential targets for the diagnosis and treatment of acute lymphoblastic leukemia (ALL). . . . . Suppressor . . REF000626 ICD-11: 2B33 Acute lymphoblastic leukemia CELL00020; CELL00105 Kasumi-1; KG-1; primary T cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Gluconeogenesis (hsa00010); Apoptosis (hsa04210) Cell ferroptosis; Cell proliferation; Cell apoptosis
unique00208 The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in leukemia CCRF-CEM cells via caspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis. Inducer . . . . . . REF000272 ICD-11: 2B33 Myeloid leukaemia CELL00080 CCRF-CEM Apoptosis (hsa04210); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01746 FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis. . . . . Suppressor . Thirty BALB/c nude mice (20~22 g, five weeks) were SiPeiFu Biotechnology Co., Ltd. (Beijing, China). Animal experiment was conducted in accordance with China Animal Welfare Legislation and was approved by the Ethics Committee of our hospital. U2OS cells (1 x 106 cells) were subcutaneously injected into mice to establish osteosarcoma mice models. The mice were randomized into Lv-si-NC and Lv-si-FANCD2 groups (n = 6). After modeling, lentivirus-packaged si-FANCD2-1 and si-NC were locally injected into tumor tissues of mice in the Lv-si-FANCD2 and Lv-si-NC groups, respectively. They were euthanized by intraperitoneal injection of sodium pentobarbital (50 mg/kg) after 28 days, the tumor tissues were collected and weight was measured. REF000966 ICD-11: 2B51 Osteosarcoma CELL00113; CELL00055; CELL00269 MG-63; U2OS; hFOB1.19 JAK-STAT signaling pathway (hsa04630); Ferroptosis (hsa04216) Cell ferroptosis
unique00849 SOCS1 impacts the pattern of secreted products in cells with active p53 and is required for the expression of a selective set of p53 target genes including those involved in ferroptosis. SOCS1 can use several mechanisms to activate p53, including promotion of serine-15 phosphorylation by ATM/ATR kinases and inhibition of the p53 repressor KAP1 in osteosarcoma cell lines. . . . . Driver . . REF000029 ICD-11: 2B51 Osteosarcoma CELL00055; CELL00101 U2OS; IMR90 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00090 Phenethyl isothiocyanate (PEITC) induces ferroptosis, autophagy, and apoptosis in K7M2 osteosarcoma cells by activating the ROS-related MAPK signaling pathway. Inducer . . . . . Male BALB/c mice, aged 4 weeks (14-16 g), were purchased from SPF (Beijing) Biotechnology Co., Ltd. K7M2 osteosarcoma cells were harvested and suspended in PBS at 4 . Mice were anesthetized with isoflurane. The left hindlimbs were shaved and cleaned with 75% ethanol. The knees of the mice were flexed beyond 90 and the cortex of the proximal tibial crest was penetrated using a 25 gauge needle by a rotating action. Once the tibial bone cortex was penetrated, the needles were further inserted 2 mm along the diaphysis, followed by injection of 10 uL of K7M2 osteosarcoma cells (5 x 105 cells) into the tibia. REF000143 ICD-11: 2B51 Osteosarcoma CELL00589 K7M2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell proliferation; Cell apoptosis; Cell autophagy
unique00110 Phenethyl isothiocyanate (PEITC) reduced cell viability, inhibited proliferation, caused #REF!/M cell cycle arrest, altered iron metabolism, induced GSH depletion, generated ROS, activated MAPK signaling pathway, and triggered multiple cell death modalities, mainly ferroptosis, apoptosis, and autophagy, in human osteosarcoma cells. Inducer . . . . . . REF000164 ICD-11: 2B51 Osteosarcoma CELL00014; CELL00055; CELL00113; CELL00245 MNNG/HOS; U-2 OS; MG-63; 143B Ferroptosis (hsa04216); Apoptosis (hsa04210); Autophagy (hsa04140) Cell ferroptosis; Cell apoptosis; Cell autophagy; Cell proliferation
unique01687 Both HILPDA and MUC1 were reported ferroptosis-related regulators. Interfering HILPDA and MUC1 expression would inhibit tumor cell proliferation and migration, and MUC1 might improve the ferroptosis resistance of osteosarcoma (OS) cells. . . . . Driver . . REF000901 ICD-11: 2B51 Osteosarcoma CELL00055; CELL00014 U2OS; MNNG/HOS Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
dupunique00849 SOCS1 impacts the pattern of secreted products in cells with active p53 and is required for the expression of a selective set of p53 target genes including those involved in ferroptosis. SOCS1 can use several mechanisms to activate p53, including promotion of serine-15 phosphorylation by ATM/ATR kinases and inhibition of the p53 repressor KAP1 in osteosarcoma cell lines. . . . . Driver . . REF000029 ICD-11: 2B51 Osteosarcoma CELL00055; CELL00101 U2OS; IMR90 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01840 ATG13 and ATG3 are required for ferroptosis-associated lipid ROS accumulation. Ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis in fibrosarcoma HT1080 cells. . . . . Driver . . REF000014 ICD-11: 2B53 Fibrosarcoma CELL10119; CELL00095 MEFs; HT1080 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00199 Diallyl trisulfide (DATS) and dimethyl trisulfide (DMTS) inhibit the erastin-induced ferroptotic cell death in fibrosarcoma HT1080 cells. Therefore, daily uptake of these ingredients in plant foods is associated with making the cells resistant to ferroptotic cell deathin vivo. Suppressor . . . . . . REF000263 ICD-11: 2B53 Fibrosarcoma CELL00095 HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01837 Among the screen hits, many reported ferroptosis genes were identified, such as pentose phosphate pathway (PPP) gene G6PDX. Ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis in fibrosarcoma HT1080 cells. . . . . Driver . . REF000014 ICD-11: 2B53 Fibrosarcoma CELL10119; CELL00095 MEF; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01838 ATG13 and ATG3 are required for ferroptosis-associated lipid ROS accumulation. Ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis in fibrosarcoma HT1080 cells. . . . . Driver . . REF000014 ICD-11: 2B53 Fibrosarcoma CELL10119; CELL00095 MEFs; HT1080 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00198 Diallyl trisulfide (DATS) and dimethyl trisulfide (DMTS) inhibit the erastin-induced ferroptotic cell death in fibrosarcoma HT1080 cells. Therefore, daily uptake of these ingredients in plant foods is associated with making the cells resistant to ferroptotic cell deathin vivo. Suppressor . . . . . . REF000263 ICD-11: 2B53 Fibrosarcoma CELL00095 HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01839 Knockout of other autophagy genes, such as ULK1/2 and ATG5, and pharmacological inhibition of PI3 kinase all led to significantly lower levels of erastin-induced ferroptosis in a dose- and time-dependent manner in fibrosarcoma HT1080 cells. . . . . Driver . . REF000014 ICD-11: 2B53 Fibrosarcoma CELL10119; CELL00095 MEF; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01011 Reduced NCOA4 expression resulted from a lower rate of hypoxic NCOA4 transcription combined with a micro RNA 6862-5p-dependent degradation of NCOA4 mRNA, the latter being regulated by c-jun N-terminal kinase (JNK). Pharmacological inhibition of JNK under hypoxia increased NCOA4 and prevented FTMT induction in fibrosarcoma HT1080 cells. . . . . Suppressor . . REF000216 ICD-11: 2B53 Fibrosarcoma CELL00095 HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01836 The study identified specific roles for RPL8, IREB2, ATP5G3, TTC35, CS and ACSF2 in erastin-induced ferroptosis. A plausible new hypothesis to emerge from these data is that CS and ACSF2 are required to synthesize a specific lipid precursor necessary for death in fibrosarcoma HT1080 cells. . . . . Driver . . REF000001 ICD-11: 2B53 Fibrosarcoma CELL00095; CELL00143; CELL00055; CELL00057; CELL10119; CELL10064; CELL10065; CELL10066; CELL00487; CELL00350 HT-1080; Calu-1; U2OS; 293-T; MEFs; BJeH; BJeHLT; BJeLR; DRD; TC32; SK-ES-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00825 Oncogenic RAS ( HRAS, NRAS, KRAS) selectively modulates cell death pathways triggered by cytotoxic stimuli in rhabdomyosarcoma RMS13 cells. In conclusion, our discovery of an increased resistance to oxidative stress imposed by oncogenic RAS mutants in RMS13 cells has important implications for the development of targeted therapies for rhabdomyosarcoma (RMS). . . . . Driver . . REF000006 ICD-11: 2B55 Rhabdomyosarcoma CELL00587 RMS13 Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); PI3K-Akt signaling pathway (hsa04151); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00826 Oncogenic RAS (HRAS, NRAS, KRAS) selectively modulates cell death pathways triggered by cytotoxic stimuli in rhabdomyosarcoma RMS13 cells. In conclusion, our discovery of an increased resistance to oxidative stress imposed by oncogenic RAS mutants in RMS13 cells has important implications for the development of targeted therapies for rhabdomyosarcoma (RMS). . . . . Driver . . REF000006 ICD-11: 2B55 Rhabdomyosarcoma CELL00587 RMS13 Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); PI3K-Akt signaling pathway (hsa04151); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00824 Oncogenic RAS (HRAS, NRAS, KRAS) selectively modulates cell death pathways triggered by cytotoxic stimuli in rhabdomyosarcoma RMS13 cells. In conclusion, our discovery of an increased resistance to oxidative stress imposed by oncogenic RAS mutants in RMS13 cells has important implications for the development of targeted therapies for rhabdomyosarcoma (RMS). . . . . Driver . . REF000006 ICD-11: 2B55 Rhabdomyosarcoma CELL00587 RMS13 Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); PI3K-Akt signaling pathway (hsa04151); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00361 Punicic acid is highly cytotoxic to HCT-116 colorectal and FaDu hypopharyngeal carcinoma cells grown either in monolayers or as three-dimensional spheroids. It induces significant lipid peroxidation and its effects are prevented by the addition of ferroptosis inhibitors. Inducer . . . . . . REF000491 ICD-11: 2B6D Hypopharyngeal carcinoma CELL00161; CELL00087 FaDu; HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01728 LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells. . . . . Suppressor . A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse). REF000949 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00184 TE-1; KYSE-30 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01729 LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells. . . . . Suppressor . A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse). REF000949 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00184 TE-1; KYSE-30 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01730 LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells. . . . . Suppressor . A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse). REF000949 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00184 TE-1; KYSE-30 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01727 LINC01004 recruited Spi-1 proto-oncogene (SPI1) in nucleus of TAMs to induce transcriptional activation of SIGLEC9. SIGLEC9 interacted with mucin 1 (MUC1). MUC1 overexpression in esophageal squamous cell carcinoma (ESCC) induced M2 skewing of TAMs, enhanced radioresistance and immunosuppression, and promoted nuclear translocation of -catenin to suppress radiotherapy-induced ferroptosis of ESCC cells. . . . . Suppressor . A total of 128 immune active female C57BL/6 mice (6 weeks old) were procured from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). ESCC cells (TE-1 and KYSE-30) resuspended in PBS were mixed with Matrigel and subcutaneously injected into the mice (1 x 106 cells per mouse) at the right flank to induce subcutaneous tumors. When the tumor size reached around 150 mm3, the tumor site was locally exposed to irradiation (2 Gy/d for consecutive 4 d). For antibody injection, the mice were injected with IgG or Anti-SIGECE on day 1, 7, or 14 after the first irradiation exposure. After 28 d, the mice were euthanized via overdosed barbiturate (150 mg/kg). The subcutaneous tumors were collected for IHC. Another group of ESCC cells were injected into mice via tail vein (2 x 106 cells per mouse). REF000949 ICD-11: 2B70 Esophageal squamous cell carcinoma CELL00228; CELL00184 TE-1; KYSE-30 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01571 ARF6, as a downstream effector of the Kirsten rat sarcoma viral oncogene (Kras)/extracellular signal-regulated kinases (ERK) signaling pathway, may increase proliferation and induce the Warburg effect in gastric cancer (GC) cells. ARF6 may control capecitabine resistance via several routes. . . . . Suppressor . . REF000780 ICD-11: 2B72 Gastric cancer CELL00322; CELL00124; CELL00261; CELL00071; CELL00114; CELL00006; CELL00290 GES-1; SGC-7901; BGC-823; AGS; MKN-45; SNU-1; MGC80-3 Ferroptosis (hsa04216); Ras signaling pathway (hsa04014) Cell ferroptosis; Cell proliferation
unique01400 Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in gastric cancer cells. And circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3. . . . . Driver . Nude mice (5-week old; Shanghai SLAC Laboratory Animals, Shanghai, China) were arbitrarily divided into two groups (n = 5). AGS cells (1 x 106 ) stably expressing circ_0000190 were inoculated into the flank of the nude mice. Tumor volume was monitored every 4 d with the method of (length x width2 )/2. These mice were euthanized after 28-d inoculation. REF000647 ICD-11: 2B72 Gastric cancer CELL00071; CELL00104; CELL00192; CELL00174 AGS; KATO III; MKN1; HGC27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01737 E-cadherin (CDH1) is a biomarker predicting the sensitivity to ferroptosis of diffuse-type gastric cancer (DGC) cells, both in primary tumor tissue and in circulation, thus guiding the usage of future ferroptosis-inducing therapeutics for the treatment of DGC. . . . . Suppressor . 7.5 X 106 SNU16 sgCDH1 cells expressing a vector, wild-type E-cadherin, or the D291N mutant in 100 ul 1:1 Matrigel: serum-free RPMI were injected into the left flank of athymicnu/numice (Envigo). Tumor growth was monitored every 3 days by caliper. Once tumors reached a mean volume of 150 mm3, mice with each tumor type were randomly grouped into two groups. IKE (MedChemExpress) was resuspended in a solution of 65% D5W (5% dextrose in water), 5% Tween-80, and 30% PEG-400. Mice were then treated daily with either 40 mg/kg IKE or the vehicle via i.p. injection. REF000956 ICD-11: 2B72 Gastric cancer CELL00336; CELL00057; CELL00288 SNU16; 293T; SNU668 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique01402 Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in gastric cancer cells. And circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3. . . . . Driver . Nude mice (5-week old; Shanghai SLAC Laboratory Animals, Shanghai, China) were arbitrarily divided into two groups (n = 5). AGS cells (1 x 106 ) stably expressing circ_0000190 were inoculated into the flank of the nude mice. Tumor volume was monitored every 4 d with the method of (length x width2 )/2. These mice were euthanized after 28-d inoculation. REF000647 ICD-11: 2B72 Gastric cancer CELL00071; CELL00104; CELL00192; CELL00174 AGS; KATO III; MKN1; HGC27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01401 Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in gastric cancer cells. And circ_0000190 suppressed GC progression via miR-382-5p-dependent regulation of ZNRF3. . . . . Suppressor . Nude mice (5-week old; Shanghai SLAC Laboratory Animals, Shanghai, China) were arbitrarily divided into two groups (n = 5). AGS cells (1 x 106 ) stably expressing circ_0000190 were inoculated into the flank of the nude mice. Tumor volume was monitored every 4 d with the method of (length x width2 )/2. These mice were euthanized after 28-d inoculation. REF000647 ICD-11: 2B72 Gastric cancer CELL00071; CELL00104; CELL00192; CELL00174 AGS; KATO III; MKN1; HGC27 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01059 The expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. . . . . Driver . . REF000279 ICD-11: 2B72 Gastric cancer CELL00071; CELL00193; CELL00114; CELL00023; CELL00338; CELL00339; CELL00288; CELL00454; CELL00497; CELL00496; CELL00011 AGS; MKN-28; MKN-45; NCI-N87; SNU-484; SNU-601; SNU-668; SNU-719; YCC-6; YCC-16; Hs746T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01060 The expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. . . . . Driver . . REF000279 ICD-11: 2B72 Gastric cancer CELL00071; CELL00193; CELL00114; CELL00023; CELL00338; CELL00339; CELL00288; CELL00454; CELL00497; CELL00496; CELL00011 AGS; MKN-28; MKN-45; NCI-N87; SNU-484; SNU-601; SNU-668; SNU-719; YCC-6; YCC-16; Hs746T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01085 ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment. . . . . Suppressor . BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection. REF000315 ICD-11: 2B90 Colon cancer CELL00561; CELL00540 CT26; 4T1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01092 CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer. . . . . Driver . . REF000331 ICD-11: 2B90 Colon cancer CELL00087; CELL00133 HCT116; SW620 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
dupunique01085 ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment. . . . . Driver . BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 105 cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 105 cells/mouse) and mammary carcinoma 4T1 (2 x 104 cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection. REF000315 ICD-11: 2B90 Colon cancer CELL00561; CELL00540 CT26; 4T1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
dupunique01092 CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer. . . . . Driver . . REF000331 ICD-11: 2B90 Colon cancer CELL00087; CELL00133 HCT116; SW620 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Hippo signaling pathway (hsa04390) Cell ferroptosis; Cell proliferation
unique00210 The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in CCRF-CEM cellsviacaspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis in colon cancer. Inducer . . . . . . REF000272 ICD-11: 2B90 Colon cancer CELL00087; CELL00601 HCT116; CC531 Apoptosis (hsa04210); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01138 Circ_0007142 regulated cancer progression and ferroptosis in colorectal cancer (CRC) cells partly by acting on the miR-874-3p/GDPD5 axis. This is a specific regulatory network for ferroptosis in CRC, and CRC treatment might be improved with circ_0007142 as a therapeutic target aiming at ferroptosis. . . . . Suppressor . 3 x 106 HCT116 cells with stable transfection of lentiviral vectors sh-circ_0007142 or sh-NC were harvested and resuspended in 0.2 mL PBS. Six-week-old male BALB/c nude mice (n = 12) from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) were injected with the prepared cell suspension (6 mice/group). During the 4-week observation period, tumour volume (length x width2/2) was detected every week. REF000372 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00133; CELL00018; CELL00267 HCT116; SW620; SW480; FHC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique00975 b-elemene in combination with cetuximab was shown to induce iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of HO-1 and transferrin, and downregulation of negative regulatory proteins for ferroptosis (GPX4, SLC7A11, FTH1, glutaminase, and SLC40A1) in KRAS mutant colorectal cancer cells. Inducer . . . . . 5-week-old female BALB/c nude were purchased from Shanghai Slac Laboratory Animal Co., Ltd. HCT116-luc cells were digested and washed by cold PBS for three times, and the final concentration was 2.5 x 106/ml in cold PBS. A volume of 100 ul cell suspension was injected subcutaneously into right dorsal flank of mice. When the tumor tissue in the subcutaneous was macroscopic, the tumor tissues were dissected and embedded into the mesentery of mice. REF000162 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00109; CELL00046 HCT116; Lovo; CaCO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell proliferation; Cell migration
unique00098 Cetuximab blunts carbohydrate metabolism by blocking glucose uptake and glycolysis, beyond promoting slow but progressive ROS production. In parallel, Vitamin C disrupts iron homeostasis and further increases ROS levels ultimately leading to ferroptosis. Considering that high-dose VitC is known to be safe in cancer patients, this findings might have clinical impact on colorectal cancer patients treated with anti-EGFR therapies. Inducer . . . . . The PDX models used in this study were derived from patients (CRC0078 and CRC0121) carrying a quadruple wild-type (KRAS,NRAS,BRAF, andPIK3CA) colorectal tumor. Established tumors (average volume 300 or 500 mm3, as indicated) were treated with the following regimens, either single-agent or in combination: VitC (Sigma, 4 g/kg, intraperitoneal, daily-5 days per week), cetuximab (Merck, 10 mg/kg, intraperitoneal, twice weekly). REF000149 ICD-11: 2B91 Colorectal cancer CELL00301; CELL00420; CELL00458 DiFi; CCK81; C75; IRCC-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00197 Dichloroacetate (DCA) could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA-mediated attenuation on colorectal cancer cell stemness. And DCA can attenuate the stemness of colorectal CSCs without affecting the viability of colorectal cancer cells. Inducer . . . . . . REF000261 ICD-11: 2B91 Colorectal cancer CELL00096; CELL00087 HT-29; HCT-116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell migration; Cell stemness
unique00362 Punicic acid is highly cytotoxic to HCT-116 colorectal carcinoma and FaDu hypopharyngeal carcinoma cells grown either in monolayers or as three-dimensional spheroids. It induces significant lipid peroxidation and its effects are prevented by the addition of ferroptosis inhibitors. Inducer . . . . . . REF000491 ICD-11: 2B91 Colorectal cancer CELL00161; CELL00087 FaDu; HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00974 b-elemene in combination with cetuximab was shown to induce iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of HO-1 and transferrin, and downregulation of negative regulatory proteins for ferroptosis (GPX4, SLC7A11, FTH1, glutaminase, and SLC40A1) in KRAS mutant colorectal cancer cells. Inducer . . . . . 5-week-old female BALB/c nude were purchased from Shanghai Slac Laboratory Animal Co., Ltd. HCT116-luc cells were digested and washed by cold PBS for three times, and the final concentration was 2.5 x 106/ml in cold PBS. A volume of 100 ul cell suspension was injected subcutaneously into right dorsal flank of mice. When the tumor tissue in the subcutaneous was macroscopic, the tumor tissues were dissected and embedded into the mesentery of mice. REF000162 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00109; CELL00046 HCT116; Lovo; CaCO2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis; Cell proliferation; Cell migration
unique00097 Cetuximab blunts carbohydrate metabolism by blocking glucose uptake and glycolysis, beyond promoting slow but progressive ROS production. In parallel, Vitamin C disrupts iron homeostasis and further increases ROS levels ultimately leading to ferroptosis. Considering that high-dose VitC is known to be safe in cancer patients, this findings might have clinical impact on colorectal cancer patients treated with anti-EGFR therapies. Inducer . . . . . The PDX models used in this study were derived from patients (CRC0078 and CRC0121) carrying a quadruple wild-type (KRAS,NRAS,BRAF, andPIK3CA) colorectal tumor. Established tumors (average volume 300 or 500 mm3, as indicated) were treated with the following regimens, either single-agent or in combination: VitC (Sigma, 4 g/kg, intraperitoneal, daily-5 days per week), cetuximab (Merck, 10 mg/kg, intraperitoneal, twice weekly). REF000149 ICD-11: 2B91 Colorectal cancer CELL00301; CELL00420; CELL00458 DiFi; CCK81; C75; IRCC-10A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01139 Circ_0007142 regulated cancer progression and ferroptosis in colorectal cancer (CRC) cells partly by acting on the miR-874-3p/GDPD5 axis. This is a specific regulatory network for ferroptosis in CRC, and CRC treatment might be improved with circ_0007142 as a therapeutic target aiming at ferroptosis. . . . . Driver . 3 x 106 HCT116 cells with stable transfection of lentiviral vectors sh-circ_0007142 or sh-NC were harvested and resuspended in 0.2 mL PBS. Six-week-old male BALB/c nude mice (n = 12) from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) were injected with the prepared cell suspension (6 mice/group). During the 4-week observation period, tumour volume (length x width2/2) was detected every week. REF000372 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00133; CELL00018; CELL00267 HCT116; SW620; SW480; FHC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01270 MiR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. In addition, SAPK/JNK is the upstream molecule of p53. MiR-539 is a new therapeutic target for colorectal cancer (CRC) patients. . . . . Suppressor . Six 4-week-old male BALB/c nude mice were ordered from the Shanghai Laboratory Animal Center (Shanghai SLAC Laboratory Animal Co., Ltd., China). A total of 5 x 106 TIPE+/+ SW480 cells were suspended in 100 uL of PBS and subcutaneously injected into the right axilla flank of each nude mouse, and the same amount of vector SW480 cells was into the left. At 2 weeks after inoculation, the xenograft tumor size was measured using Vernier calipers every 2 days. REF000524 ICD-11: 2B91 Colorectal cancer CELL00087; CELL00018; CELL00057 HCT116; SW480; 293T Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation
unique00171 The anticancer effect of the combined treatment of SN38 and EP is related to changes in the redox-homeostasis of cancer cells, leading to cell death via apoptosis and/or ferroptosis. Thus, electroporation has a potential to increase the sensitivity of colorectal cancer cells to conventional anticancer therapy with SN38. Inducer . . . . . . REF000226 ICD-11: 2B91 Colorectal cancer CELL00573 Colon26 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01517 The downregulated ferroptosis-associated gene MT1G and revealed that a low MT1G level displayed a worse prognosis in colorectal cancer patients. In addition, the MT1G expression was closely related to the immune microenvironment and involved in the progression of tumors. . . . . Suppressor . . REF000734 ICD-11: 2B91 Colorectal cancer CELL00250; CELL00087; CELL00118 HCT8; HCT116; NCM460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00994 MiR-326 was negatively regulated by circABCB10, while CCL5 was positively regulated by it, and circABCB10 served as a sponge of miR-326 to regulate the CCL5 expression in rectal cancer cells. CircABCB10 silence promoted rectal cancer cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis, suggesting a potential therapeutic target for rectal cancer therapy. . . . . Suppressor . BALB/c nude mice (female, 4-6 weeks of age, N = 6) were used to perform the xenograft assays. HR-8348 cells were stably transfected with lentivirus containing sh-circ-ABCB10 or sh-NC and then subcutaneously injected into the flanks of the nude mice. After one week following the inoculation, the tumor size was examined every week and the tumor volume was calculated. After 4 weeks, all mice were sacrificed and tumor masses were weighted and harvested for further molecular analysis. REF000193 ICD-11: 2B92 Rectal cancer CELL00225; CELL00331 SW837; HR-8348 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00996 MiR-326 was negatively regulated by circABCB10, while CCL5 was positively regulated by it, and circABCB10 served as a sponge of miR-326 to regulate the CCL5 expression in rectal cancer cells. CircABCB10 silence promoted rectal cancer cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis, suggesting a potential therapeutic target for rectal cancer therapy. . . . . Suppressor . BALB/c nude mice (female, 4-6 weeks of age, N = 6) were used to perform the xenograft assays. HR-8348 cells were stably transfected with lentivirus containing sh-circ-ABCB10 or sh-NC and then subcutaneously injected into the flanks of the nude mice. After one week following the inoculation, the tumor size was examined every week and the tumor volume was calculated. After 4 weeks, all mice were sacrificed and tumor masses were weighted and harvested for further molecular analysis. REF000193 ICD-11: 2B92 Rectal cancer CELL00225; CELL00331 SW837; HR-8348 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00995 MiR-326 was negatively regulated by circABCB10, while CCL5 was positively regulated by it, and circABCB10 served as a sponge of miR-326 to regulate the CCL5 expression in rectal cancer cells. CircABCB10 silence promoted rectal cancer cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis, suggesting a potential therapeutic target for rectal cancer therapy. . . . . Driver . BALB/c nude mice (female, 4-6 weeks of age, N = 6) were used to perform the xenograft assays. HR-8348 cells were stably transfected with lentivirus containing sh-circ-ABCB10 or sh-NC and then subcutaneously injected into the flanks of the nude mice. After one week following the inoculation, the tumor size was examined every week and the tumor volume was calculated. After 4 weeks, all mice were sacrificed and tumor masses were weighted and harvested for further molecular analysis. REF000193 ICD-11: 2B92 Rectal cancer CELL00225; CELL00331 SW837; HR-8348 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00568 A2M-AS1 could directly interact with the poly (rC) binding protein 3 (PCBP3), which plays an important role in the process of iron metabolism, thereby promoting the ferroptosis in pancreatic cancer. . . . . Driver . Male BALB/c nude mice (5 weeks old; 16-18 g) were obtained from the Animal Center of Guangxi Medical University and grown under specific pathogen-free conditions. The mice (n = 20) were randomly divided into four groups; Vector group, A2M-AS1 group, Vector + Erastin group, and A2M-AS1 + Erastin group. The Vector and Vector + Erastin groups were injected with 106 cells that stably expressing the lentiviral vector, whereas the other two groups were injected with 106 cells that stably overexpressing A2M-AS1. On the 7th day after inoculation, the Vector + Erastin and A2M-AS1 + Erastin groups were intraperitoneally injected with a 100-uL Erastin solution (40 mg/kg) once every 2 days. REF000798 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00073; CELL00278 PANC-1; AsPC-1; HPDE Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01093 PDK4 inhibits ferroptosis by blocking pyruvate dehydrogenase-dependent pyruvate oxidation. Inhibiting PDK4 enhances the anticancer activity of system xcinhibitors in vitro and in suitable preclinical mouse models (e.g., a high-fat diet diabetes model). Individuals with pancreatic ductal adenocarcinoma (PDAC) and diabetes might be particularly suitable for this kind of therapeutic approach. . . . . Suppressor . At 6 weeks of age, male C57BL/6J mice received standard diet (SCD) or high-fat diet (HFD; 5.24 kcal/g with 20% energy derived from protein, 60% from fat, and 20% from carbohydrate; Research Diets; D12492) for 12 weeks. Then the mouse PDAC cell lineKPC (male) was implanted subcutaneously into the right abdomen of SCD and HFD mice. Once the tumors reached 60-80 mm3 at day 7, tumor-bearing mice were treated with IKE (40 mg/kg, i.p.,once every other day) or the ferroptosis inhibitor liproxstatin-1 (10 mg/kg, i.p., once every other day) or the PDK inhibitor dichloroacetate (DCA, 50 mg/kg, i.p., once every other day) under the corresponding diet. REF000333 ICD-11: 2C10.0 Pancreatic ductal adenocarcinoma CELL00120; CELL00013; CELL10107 PANC1; MIAPaCa2; PHsPDAC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Citrate cycle (hsa00020) Cell ferroptosis
unique01570 SIRT6 promoted ferroptosis and inhibited glycolysis through inactivating the NF-B signaling pathway in pancreatic cancer (PC). These findings suggested that SIRT6 may become a therapeutic target for PC. . . . . Suppressor . A total of 20 SPF BALB/C nude mice were randomly divided into two groups [SIRT6 group (n = 10) and vector group (n = 10)]. PANC-1 cells (1 x 106) in 200 ul phosphate-buffered saline were subcutaneously inoculated in nude mice of each group. The tumor volume was recorded every 7 days. REF000779 ICD-11: 2C10 Pancreatic cancer CELL00222; CELL00008; CELL00120; CELL00530; CELL00278 SW1990; BXPC-3; PANC-1; PC-2; HPDE Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064); Gluconeogenesis (hsa00010) Cell ferroptosis; Cell proliferation
unique00615 Carabrone showed cytotoxicity against SW1990 pancreatic cancer cells through proliferation and migration inhibition mediating via the Hippo signaling pathway and finally induced the cell death through ferroptosis. Inducer . . . . . . REF000840 ICD-11: 2C10 Pancreatic cancer CELL00222; CELL00160; CELL00047; CELL00120 SW1990; CFPAC-1; Capan-2; PANC-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00179 Irisin Is a positive regulator for ferroptosis in pancreatic cancer. There was a dramatic downregulation of p62 expression, which inhibited NRF2 degradation and enhanced NRF2 nuclear accumulation after 12h of irisin and erastin co-treatment, although irisin or erastin alone did not affect p62 levels. Inducer . . . . . . REF000237 ICD-11: 2C10 Pancreatic cancer CELL00120 PANC-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00069 Ruscogenin exerts anticancer function in pancreatic cancer cells by inducing ferroptosis. Ruscogenin improved ROS generation and increased intracellular iron by regulating transferrin and ferroportin. Inducer . . . . . A total of 15 six-week-old female BALB/c nude mice (25.2-25.9 g) were purchased from SLAC Animal Laboratories. Approximately 1 x 106 BxPC-3 cells were subcutaneously implanted into the right flank of the nude mice. The tumors were allowed to grow to approximately 120 mm3 in size and a total of 15 tumor-bearing mice were divided randomly into 3 groups (n = 5 per group). Group 1 was injected with 0.1 ml PBS as control; group 2 and 3 received 5 and 10 mg/kg ruscogenin, respectively twice per week. REF000119 ICD-11: 2C10 Pancreatic cancer CELL00008; CELL00222; CELL00120; CELL00073; CELL00149 BxPC-3; SW1990; PANC-1; AsPC-1; HPDE6-C7 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00569 A2M-AS1 could directly interact with the poly (rC) binding protein 3 (PCBP3), which plays an important role in the process of iron metabolism, thereby promoting the ferroptosis in pancreatic cancer. . . . . Suppressor . Male BALB/c nude mice (5 weeks old; 16-18 g) were obtained from the Animal Center of Guangxi Medical University and grown under specific pathogen-free conditions. The mice (n = 20) were randomly divided into four groups; Vector group, A2M-AS1 group, Vector + Erastin group, and A2M-AS1 + Erastin group. The Vector and Vector + Erastin groups were injected with 106 cells that stably expressing the lentiviral vector, whereas the other two groups were injected with 106 cells that stably overexpressing A2M-AS1. On the 7th day after inoculation, the Vector + Erastin and A2M-AS1 + Erastin groups were intraperitoneally injected with a 100-uL Erastin solution (40 mg/kg) once every 2 days. REF000798 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00073; CELL00278 PANC-1; AsPC-1; HPDE Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01853 ESCRT III-mediated plasma membrane repair can reduce lipid peroxidation and DAMPs (e.g., HMGB1) during ferroptosis. The accumulation of ESCRT-III subunits (e.g., CHMP5 and CHMP6) in the plasma membrane are increased by classical ferroptosis activators (e.g., erastin and RSL3), which relies on endoplasmic reticulum stress and calcium influx in pancreatic ductal adenocarcinoma cells PANC1. . . . . Suppressor . To generate murine subcutaneous tumors, 5 x 106 PANC1 or HepG2 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude or B6 mice. Once the tumors reached 50-70 mm3 at day 7, mice were randomly allocated into groups and treated with (1S-3R)-RSL3 (30 mg/kg; i.p., once every other day) for 2 weeks. REF000115 ICD-11: 2C10 Pancreatic ductal adenocarcinoma CELL00120; CELL00048 PANC1; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01852 The accumulation of ESCRT-III subunits (e.g., CHMP5 and CHMP6) in the plasma membrane are increased by classical ferroptosis activators (e.g., erastin and RSL3), which relies on endoplasmic reticulum stress and calcium influx in pancreatic ductal adenocarcinoma cells PANC1. . . . . Suppressor . To generate murine subcutaneous tumors, 5 x 106 PANC1 or HepG2 cells in 100 ul PBS were injected subcutaneously to the right of the dorsal midline in 6- to 8-week-old athymic nude or B6 mice. Once the tumors reached 50-70 mm3 at day 7, mice were randomly allocated into groups and treated with (1S-3R)-RSL3 (30 mg/kg; i.p., once every other day) for 2 weeks. REF000115 ICD-11: 2C10 Pancreatic ductal adenocarcinoma CELL00120; CELL00048 PANC1; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01196 The prognostic model was established based on four ferroptosis-related genes (ENPP2, ATG4D, SLC2A1 and MAP3K5), and the risk score was demonstrated to be an independent risk factor in pancreatic cancer (HR 1.648, 95% CI 1.335-2.035, p < 0.001). . . . . Driver . . REF000445 ICD-11: 2C10 Pancreatic cancer . . Ferroptosis (hsa04216) Cell ferroptosis
unique01012 The study screened 571 UPS-related E1, E2, and E3 genes in a human pancreatic cancer cell line (PANC1) and identified the upregulation of NEDD4-like E3 ubiquitin protein ligase (NEDD4L) as a novel ferroptosis suppressor. NEDD4L-mediated LTF protein degradation inhibits intracellular iron accumulation and subsequent oxidative damage-mediated ferroptotic cell death. . . . . Suppressor . . REF000217 ICD-11: 2C10 Pancreatic cancer CELL00120; CELL00608 PANC1; OVCAR3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00003 The synergistic cell death induced by the combined treatment with Cotylenin A (CN-A) and phenethyl isothiocyanate (PEITC) is mainly due to the induction of ferroptosis. Therefore, the combination of CN-A and PEITC has potential as a novel therapeutic strategy against pancreatic cancer. Inducer . . . . . . REF000012 ICD-11: 2C10 Pancreatic cancer CELL00013; CELL00120; CELL00160 MIAPaCa-2; PANC-1; CFPAC-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00002 The synergistic cell death induced by the combined treatment with Cotylenin A (CN-A) and phenethyl isothiocyanate (PEITC) is mainly due to the induction of ferroptosis. Therefore, the combination of CN-A and PEITC has potential as a novel therapeutic strategy against pancreatic cancer. Inducer . . . . . . REF000012 ICD-11: 2C10 Pancreatic cancer CELL00013; CELL00120; CELL00160 MIAPaCa-2; PANC-1; CFPAC-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01841 This study reveals the protective effects of XJB-5-131 and JP4-039 in pancreatic ductal adenocarcinoma BJeLR cells against erastin-induced and RSL3-induced ferroptosis. Suppressor . . . . . . REF000015 ICD-11: 2C10 Pancreatic ductal adenocarcinoma CELL10066; CELL00120 BJeLR; Panc-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01842 This study reveals the protective effects of XJB-5-131 and JP4-039 in pancreatic ductal adenocarcinoma BJeLR cells against erastin-induced and RSL3-induced ferroptosis. Suppressor . . . . . . REF000015 ICD-11: 2C10 Pancreatic ductal adenocarcinoma CELL10066; CELL00120 BJeLR; Panc-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01245 Inhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant hepatocellular carcinoma (HCC). . . . . . Driver/Suppressor . REF000494 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00304; CELL00098; CELL00048; CELL00012; CELL00016 L02; Hep3B; HepG2; Huh7; PLC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01473 AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in hepatocellular carcinoma (HCC). AKR1C3 inhibitors may be used in conjunction with sorafenib to become a better therapeutic target for HCC. . . . . Suppressor . . REF000703 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00048 Huh7; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis; Cell proliferation
unique01006 cIARS (hsa_circ_0008367) was found to be the most highly expressed circRNA after sorafenib (SF) treatment in hepatocellular carcinoma cells. cIARS may be an important circRNA, positively regulating SF-induced ferroptosis through suppressing the ALKBH5-mediated autophagy inhibition. . . . . Driver . . REF000210 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00017; CELL00012 HepG2; SMMC-7721; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01705 CircCMTM3 promoted the carcinogenesis through inhibiting ferroptosis by recruiting IGF2BP1 to increase PARK7 stability in hepatocellular carcinoma (HCC), suggesting that cicrCMTM3 may be an important marker for HCC treatment. . . . . Suppressor . Six-week-old BALB/c female athymic nude mice (SJA Laboratory Animal Co., Ltd, China) were used to construct the xenograft. The mice were randomly grouped: (1) shNC + vehicle; (2) shNC + Erastin; (3) shWTAP + Erastin; (4) shcircCMTM3 + Erastin. Briefly, HCC cells with stable silenced WTAP and circCMTM3 (2 x 106 in 0.1 mL PBS) were injected into the left flank of the mice subcutaneously. Once the tumor size reached approximately > 60 mm3, mice in the groups (2), (3), and (4) were injected with 15 mg/kg erastin. Erastin was injected twice a day for a period of time. REF000930 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00299; CELL00273; CELL00098; CELL00125; CELL00048 Huh-7; HCCLM3; THLE-2; Hep3B; Sk-Hep-1; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01075 CLTRN acts as a target of radiation, which is regulated by the NRF1/RAN/DLD protein complex, and it enhances the radiosensitivity of hepatocellular carcinoma cells through ferroptosis. . . . . Driver . . REF000309 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048 HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01609 GABARAPL1 was downregulated in hepatocellular carcinoma (HCC) tumor-repopulating cells (TRC; a type of CSLC). Its downregulation decreased the sensitivity of HCC TRC to erastin- or sorafenib-triggered ferroptosis. . . . . Driver . . REF000819 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00116; CELL00125; CELL00285; CELL00017; CELL00565; CELL00012; CELL00016; CELL00304 SNU449; SKHep1; MHCC97H; SMMC7721; LM3; Huh7; PLC/PRF/5; L02 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01354 LIFR and SHP1 (PTPN6) positively regulate ferroptosis while LCN2 negatively regulates ferroptosis. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on hepatocellular carcinoma patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. . . . . Driver . PDX tumors in cold Dulbeccos Modified Eagles Medium (DMEM) were minced into 1-2 mm3 fragments, and each fragment was subcutaneously transplanted into the dorsal flank of 6-week-old male NSG (non-obese diabetic; severe combined immunodeficiency; interleukin-2 receptor gamma chain null) mice. Tumor growth was monitored by bidimensional tumor measurements with a caliper twice a week until the endpoint. REF000613 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00098; CELL00048; CELL00110; CELL00016; CELL00308; CELL00012 HEK293T; Hep3B; HepG2; Mahlavu; PLC/PRF/5; HA59T; Tong; Huh-7; PHM; PHR Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique00829 MT-1G is a critical regulator and promising therapeutic target of sorafenib resistance in human hepatocellular carcinoma cells. Knockdown of MT-1G by RNA interference increases glutathione depletion and lipid peroxidation, which contributes to sorafenib-induced ferroptosis. . . . . Suppressor . To generate murine subcutaneous tumors, 2 x 106 Huh7 cells in control shRNA or MT-1G knockdown cells in 200 ul phosphate buffered saline were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached 80-100 mm3 at day seven, mice were randomly allocated into groups and treated with sorafenib (10 mg/kg/intraperitoneal injection (i.p.), once every other day) for two weeks. In another experiment, nude mice were injected subcutaneously with indicated Huh7 cells (2 x 106 cells/mouse) and treated with sorafenib (10 mg/kg/i.p., once every other day) with or without ATRA (0.5 mg/kg/i.p., once every other day) or PPG (10 mg/kg/i.p., once every other day) at day seven for two weeks. REF000010 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00098; CELL00012 HepaG2; Hep3B; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01467 NEAT1 can competitively bind more miR-362-3p and thus leads to less miR-362-3p-mediated MIOX inhibition, thereby increasing the sensitivity of hepatocellular carcinoma cells to ferroptosis. . . . . Driver . NU/NU nude mice were purchased from Charles River (Beijing). For xenograft models, HepG2 or HuH-7 cells (5 x 106 cells per mouse) that were transfected with the NEAT1 vector or an empty vector were injected into the left posterior flanks of 7-week-old immunodeficient female nude mice. The tumors were measured every 4 days, and tumor volume was calculated using the following formula: volume = (L x W2)/2, among which L and W are the longest and shortest diameters, respectively. When tumors reached a volume of ~50 mm3, mice were randomly allocated into groups and treated with erastin or RSL3 via intraperitoneal injection for 20 days. Mice were then sacrificed, the xenograft tumors were excised and weighted for immunohistochemistry assays. The erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma). To better dissolve erastin, we warmed the tube at 37 water base and shake it gently. REF000697 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00048; CELL00012 HEK293T; HepG2; HuH-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01069 RRM2 exerts an anti-ferroptotic role in liver cancer cells by sustaining GSH synthesis. Serum RRM2 will be useful as a biomarker to evaluate the degree to which ferroptosis is suppressed and improve diagnostic efficiency for liver cancer. . . . . Suppressor . . REF000292 ICD-11: 2C12 Hepatocellular carcinoma CELL00304; CELL00291; CELL00017; CELL00125; CELL00012; CELL00474; CELL00048 HL-7702; Bel-7402; SMMC-7721; SK-Hep-1; Huh-7; Bel-7404; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00043 1-Methylnaphthalene-4-propionate endoperoxide (MNPE) is a cell-permeable endoperoxide that generates pure singlet oxygen. MNPE treatment decreased the viabilities of mouse liver cancer cells in vitro, and that this decrease was accompanied by increases in the concentrations of both intracellular ferrous iron and the level of lipid peroxidation. Inducer . . . . . . REF000084 ICD-11: 2C12 Hepatocellular carcinoma CELL00009 Hepa 1-6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00915 A positive correlation between c-Jun O-GlcNAcylation and GSH was observed in clinical samples. Collectively, O-GlcNAcylated c-Jun represents an obstructive factor to ferroptosis, and targeting O-GlcNAcylated c-Jun might be helpful for treating liver cancer. . . . . Suppressor . Eight-week-old athymic nude mice were obtained from Bikai Laboratory Animal Crop (Bikai, Shanghai, China) and Bel-7402 cells (initial 5 x 106) were subcutaneously injected into each mouse. Dimethy sulfoxide (DMSO) or piperazine erastin (5 mg/kg, MedChemExpress, Monmouth Junction, NJ, USA) was subcutaneously injected once every day after xenografts were formed. REF000081 ICD-11: 2C12 Hepatocellular carcinoma CELL00291; CELL00017 Bel-7402; SMMC-7721 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00868 Chemical or genetic inhibition of CBS demonstrates that endogenous CBS is closely coupled with cell proliferation and cell cycle. Moreover, CH004 substantially retarded in vivo tumor growth in a xenograft mice model of liver cancer. Importantly, inhibition of CBS triggers ferroptosis in hepatocellular carcinoma. . . . . Suppressor . H22 mouse liver tumor cells were intraperitoneal injected into female ICR mice (SLAC Laboratory Animal Co. Ltd, Shanghai, China). 8 days later, mice with distended abdomen were killed, and the ascites was collected, washed and resuspended with PBS. 0.1ml cell suspension with a density of 1 x 107/ml was subcutaneously injected into the right dorsum of ICR female mice (~20g). The mice bearing H22 tumor cells were then randomized into groups (n = 8) on the following day after the implantation. Then, the mice were injected via a tail vein (i.v.) with PBS, CH004 (10 mg/kg) or cyclophosphamide (CTX, a known anticancer drug; 20 mg/kg) once per day and for 21 days. REF000050 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00057; CELL00005; CELL00440; CELL00012; CELL10119; CELL00087; CELL00567 HepG2; HEK293T; MDA-MB-231; Panc-28; Huh7; MEF; HCT116; H22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell cycle
unique01007 cIARS (hsa_circ_0008367) was found to be the most highly expressed circRNA after sorafenib (SF) treatment in hepatocellular carcinoma cells. cIARS may be an important circRNA, positively regulating SF-induced ferroptosis through suppressing the ALKBH5-mediated autophagy inhibition. . . . . Suppressor . . REF000210 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00017; CELL00012 HepG2; SMMC-7721; Huh7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01706 CircCMTM3 promoted the carcinogenesis through inhibiting ferroptosis by recruiting IGF2BP1 to increase PARK7 stability in hepatocellular carcinoma (HCC), suggesting that cicrCMTM3 may be an important marker for HCC treatment. . . . . Suppressor . Six-week-old BALB/c female athymic nude mice (SJA Laboratory Animal Co., Ltd, China) were used to construct the xenograft. The mice were randomly grouped: (1) shNC + vehicle; (2) shNC + Erastin; (3) shWTAP + Erastin; (4) shcircCMTM3 + Erastin. Briefly, HCC cells with stable silenced WTAP and circCMTM3 (2 x 106 in 0.1 mL PBS) were injected into the left flank of the mice subcutaneously. Once the tumor size reached approximately > 60 mm3, mice in the groups (2), (3), and (4) were injected with 15 mg/kg erastin. Erastin was injected twice a day for a period of time. REF000930 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00299; CELL00273; CELL00098; CELL00125; CELL00048 Huh-7; HCCLM3; THLE-2; Hep3B; Sk-Hep-1; HepG2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00686 High boric acid (BA) concentrations can directly induce ferroptosis in hepatocellular carcinoma, and such BA-induced ferroptosis can add to the cytotoxic effects of anticancer drugs sorafenib, doxorubicin and cisplatin. Inducer . . . . . . REF000911 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048 HepG2 Ferroptosis (hsa04216) Cell ferroptosis
unique01353 LIFR and SHP1 (PTPN6) positively regulate ferroptosis while LCN2 negatively regulates ferroptosis. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on hepatocellular carcinoma patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. . . . . Driver . PDX tumors in cold Dulbeccos Modified Eagles Medium (DMEM) were minced into 1-2 mm3 fragments, and each fragment was subcutaneously transplanted into the dorsal flank of 6-week-old male NSG (non-obese diabetic; severe combined immunodeficiency; interleukin-2 receptor gamma chain null) mice. Tumor growth was monitored by bidimensional tumor measurements with a caliper twice a week until the endpoint. REF000613 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00098; CELL00048; CELL00110; CELL00016; CELL00308; CELL00012 HEK293T; Hep3B; HepG2; Mahlavu; PLC/PRF/5; HA59T; Tong; Huh-7; PHM; PHR Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01352 LIFR and SHP1 (PTPN6) positively regulate ferroptosis while LCN2 negatively regulates ferroptosis. Notably, an LCN2 -neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on hepatocellular carcinoma patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. . . . . Suppressor . PDX tumors in cold Dulbeccos Modified Eagles Medium (DMEM) were minced into 1-2 mm3 fragments, and each fragment was subcutaneously transplanted into the dorsal flank of 6-week-old male NSG (non-obese diabetic; severe combined immunodeficiency; interleukin-2 receptor gamma chain null) mice. Tumor growth was monitored by bidimensional tumor measurements with a caliper twice a week until the endpoint. REF000613 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00098; CELL00048; CELL00110; CELL00016; CELL00308; CELL00012 HEK293T; Hep3B; HepG2; Mahlavu; PLC/PRF/5; HA59T; Tong; Huh-7; PHM; PHR Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis; Cell proliferation
unique01468 NEAT1 can competitively bind more miR-362-3p and thus leads to less miR-362-3p-mediated MIOX inhibition, thereby increasing the sensitivity of hepatocellular carcinoma cells to ferroptosis. . . . . Suppressor . NU/NU nude mice were purchased from Charles River (Beijing). For xenograft models, HepG2 or HuH-7 cells (5 x 106 cells per mouse) that were transfected with the NEAT1 vector or an empty vector were injected into the left posterior flanks of 7-week-old immunodeficient female nude mice. The tumors were measured every 4 days, and tumor volume was calculated using the following formula: volume = (L x W2)/2, among which L and W are the longest and shortest diameters, respectively. When tumors reached a volume of ~50 mm3, mice were randomly allocated into groups and treated with erastin or RSL3 via intraperitoneal injection for 20 days. Mice were then sacrificed, the xenograft tumors were excised and weighted for immunohistochemistry assays. The erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma). To better dissolve erastin, we warmed the tube at 37 water base and shake it gently. REF000697 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00048; CELL00012 HEK293T; HepG2; HuH-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01469 NEAT1 can competitively bind more miR-362-3p and thus leads to less miR-362-3p-mediated MIOX inhibition, thereby increasing the sensitivity of hepatocellular carcinoma cells to ferroptosis. . . . . Driver . NU/NU nude mice were purchased from Charles River (Beijing). For xenograft models, HepG2 or HuH-7 cells (5 x 106 cells per mouse) that were transfected with the NEAT1 vector or an empty vector were injected into the left posterior flanks of 7-week-old immunodeficient female nude mice. The tumors were measured every 4 days, and tumor volume was calculated using the following formula: volume = (L x W2)/2, among which L and W are the longest and shortest diameters, respectively. When tumors reached a volume of ~50 mm3, mice were randomly allocated into groups and treated with erastin or RSL3 via intraperitoneal injection for 20 days. Mice were then sacrificed, the xenograft tumors were excised and weighted for immunohistochemistry assays. The erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma). To better dissolve erastin, we warmed the tube at 37 water base and shake it gently. REF000697 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057; CELL00048; CELL00012 HEK293T; HepG2; HuH-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01428 Nuclear localisation of RB1CC1 correlated with lipid peroxidation in clinical lung cancer specimens. Rb1cc1 was essential for ferroptosis agonists to suppress liver tumourigenesis in mice. . . . . Driver . To evaluate the effects of drugs to strengthen the effects of IKE, cell-derived xenograft (CDX) mouse models were generated by subcutaneously injecting 2 x 106 cells per athymic nude mouse (BALB/c-nu, Spaefer, Beijing, China). When tumours were 220-250 mm3, mice were administered with IKE (50 mg/kg) daily with or without PTX (20 mg/kg), Clolar (10 mg/kg), OXA (10 mg/kg) or TMZ (40 mg/kg). Tumour growth was monitored, and sizes were calculated by 0.5 x L x W2 (L indicating length and W indicating width). REF000669 ICD-11: 2C12 Hepatocellular carcinoma CELL00048; CELL00114; CELL00056; CELL00317; CELL00045; CELL00198; CELL00222; CELL00291; CELL00096; CELL00015; CELL00143; CELL00057; CELL00245 HepG2; MKN45; H1299; PC9; A549; H226; SW1990; Bel7402; HCT29; H460; Calu1; HEK293T; 143B RHO Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
dupunique00682 PNO1 inhibits autophagy-mediated ferroptosis via GSH metabolic reprogramming as demonstrated above. We also demonstrated that PNO1 inhibition repressed SLC7A11 through p53 to promote ferroptosis. These observations suggested that sh-PNO1 could be a new target in hepatocellular carcinoma therapy. . . . . Driver . Xenograft mouse model experiments were used male BALB/c nude mice (4 weeks old) purchased from SPF Biotechnology (Beijing, China). Each mouse was injected 5 x 106 tumor cells at the volume of 100 uL into the subcutaneous tissue. The tumor volume and weight of the mice was observed every 2 days. Mice were monitored daily and the tumor volume calculated according to the equation volume = length x width2 x 1/2. REF000905 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00057 HEK293T Autophagy (hsa04140); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell autophagy
unique00953 The ferroptosis-promoting effects of miR-214 in hepatocellular carcinoma cells are attributed at least to its inhibitory effects on ATF4, which may provide a new target for therapy of hepatoma regarding ferroptosis. . . . . Driver . The 5-week-old nude mice (BALB/c) were purchased from Beijing HFK Bioscience Co., Ltd. (China). Hep3B cells (7 x 106) stably transfected with NC1 or pre-miR-214 plasmid were subcutaneously injected into the nude mice. When the tumor sizes reached approximately >50 mm3, mice in Groups B and C were treated with 15 mg/kg erastin (MCE, China) twice every day for 20 days. Mice in Group A were treated with an equal volume vehicle. REF000126 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00098 HepG2; Hep3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00954 The ferroptosis-promoting effects of miR-214 in hepatocellular carcinoma cells are attributed at least to its inhibitory effects on ATF4, which may provide a new target for therapy of hepatoma regarding ferroptosis. . . . . Suppressor . The 5-week-old nude mice (BALB/c) were purchased from Beijing HFK Bioscience Co., Ltd. (China). Hep3B cells (7 x 106) stably transfected with NC1 or pre-miR-214 plasmid were subcutaneously injected into the nude mice. When the tumor sizes reached approximately >50 mm3, mice in Groups B and C were treated with 15 mg/kg erastin (MCE, China) twice every day for 20 days. Mice in Group A were treated with an equal volume vehicle. REF000126 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00048; CELL00098 HepG2; Hep3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00822 Upon exposure to sorafenib, the Rb (RB1)-negative status of hepatocellular carcinoma cells promotes the occurrence of ferroptosis, a form of oxidative necrosis. The findings highlight the role of Rb in the response of HCC cells to sorafenib and the regulation of ferroptosis. . . . . Suppressor . Six week-old female Balb/cnude mice (Janvier, Le Genest Saint Isle, France) were injected with HCC cells (10 x 106 cells) stably transfected with the vector pGL4.51 [luc2/CMV/neo] (Promega) encoding the luciferase reporter gene luc2 (Photinus pyralis). When the first tumours appeared, mice were randomly assigned into four groups: control or shRb, receiving sorafenib administered by oral gavage (30 mg/kg/d, resuspended in Cremophore EL) or vehicle alone. REF000004 ICD-11: 2C12.02 Hepatocellular carcinoma CELL00012; CELL00476 Huh7; PLC/PRF5 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01771 GINS4 is a potential oncogene in lung adenocarcinoma (LUAD) that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD. . . . . Suppressor . The 4-wk-old female nude mice used in this study were purchased from Hunan SJA Laboratory Animal Co., Ltd (Changsha). Then, 2 x 106 GINS4 WT or KO A549 cells were injected s.c. into nude mice without matrigel. Tumor size was measured every 2 d with a caliper, and volume of tumor was calculated with the formula: L x W2 x 0.5, for L represents the longest diameter and W means the shortest diameter. Then, 2 x 106 p53 WT and KO A549 cells with shCon or shGINS4 overexpressing were injected s.c. into nude mice without matrigel. When tumors reached 60 to 100 mm3, p53 WT with shGINS4 mice were treated with ferrostatin-1 (S7243, Selleckchem) (20 mg/kg) in 2% DMSO, 50% PEG300, 5% Tween80, and 43% water by daily intraperitoneal injection. Tumors were measured three times a week. Mice were sacrificed and tumors were collected finally. Tumor tissue was made into a single-cell suspension for lipid ROS assay using Tumor Dissociation Kit (Miltenyi Biotec). REF001001 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00015; CELL00056; CELL00201; CELL00045 293T; H460; H1299; H358; A549 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01701 LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes lung adenocarcinoma (LUAD) autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. . . . . Driver . The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Second Xiangya Hospital following the Guidelines of the Care and Use of Laboratory Animals issued by the Chinese Council on Animal Research. Briefly, female BALB/c nude mice at six weeks were obtained from Hunan SJA Laboratory Animal Co. Ltd. (Hunan, China) and kept in a specific pathogen-free environment. The mice were injected subcutaneously with 2 x 106 indicated cells into the left or right flank for 21 days (PC9) or 28 days (A549) post-implantation. At the end of the experiment, the tumours were dissected and weighed. REF000927 ICD-11: 2C25.0 Lung adenocarcinoma CELL00317; CELL00045 PC9; A549 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01868 MICU1 as a key regulator for lipid peroxidation and subsequent ferroptosis under cold stress, suggesting that MICU1 can be a potential target for preventing lung adenocarcinoma cell death in organ preservation. . . . . Driver . . REF000376 ICD-11: 2C25 Lung adenocarcinoma CELL00045; CELL00483; CELL00048; CELL00095 A549; HEK293A; HepG2; HT1080 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Thermogenesis (hsa04714) Cell ferroptosis
unique00859 P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA-G3BP1 interaction displaced p53 from a G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to cell-cycle arrest, apoptosis, and ferroptosis in lung cancer cell lines. . . . . Driver . SCID mice (Hunan SJA Laboratory Animal Co. Ltd.) were injected with the indicated cells in the mammary fat pad (10 mice/group). Injected mice were imaged from both the dorsal and ventral sides every three days. REF000038 ICD-11: 2C25 Lung cancer CELL00045; CELL00306; CELL00204; CELL00085; CELL00056; CELL00342; CELL00201; CELL00317; CELL00486; CELL00309 A549; SPCA1; H522; HBE; H1299; MRC-5; H358; PC9; 95C; 95D Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01866 BMS536924, a dual inhibitor of insulin-like growth and insulin receptors, is a potent inhibitor of ferroptosis in non-small cell lung carcinoma. Suppressor . . . . . . REF000295 ICD-11: 2C25 Non-small cell lung carcinoma CELL00204; CELL00095; CELL00005 NCI-H522; HT1080; MDA MB 231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00189 Dynasore can function as a highly active inhibitor of ROS-driven types of cell death via combined modulation of the iron pool and inhibition of general ROS by simultaneously blocking two routes required for ROS and lipid-ROS driven cell death in lung cancer, respectively. Suppressor . . . . . . REF000248 ICD-11: 2C25 Lung cancer CELL00202; CELL00045; CELL00015; CELL00382; CELL00022; CELL10083; CELL00383 H441; A549; H460; H727; H520; H332m; H82 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00117 Erianin could inhibit cell proliferation, promote G2/M-phase arrest, trigger ferroptosis, and suppress migration in lung cancer cells. Inducer . . . . . H460-luc cells (2 x 106 cells in 0.1 ml phosphate-buffered saline) were subcutaneously injected into the right dorsal flank of 6-week-old female BALB/c nude mice; for the orthotopic xenograft lung tumor mouse model, a volume of 100 ul of cell suspension was injected into the right side of the lung. Tumor volume was assessed every 2 days. REF000172 ICD-11: 2C25 Lung cancer CELL00015; CELL00056 H460; H1299 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01292 Combined with lung adenocarcinoma tissue samples and mouse trials, RRM2 was found to influence lung cancer progression and affect tumor immune cell infiltration. RRM2 inhibition effectively promoted M1 macrophage polarization and suppressed M2 macrophage polarization in vitro and in vivo. . . . . Suppressor . LLC cells were cultured to prepare a single-cell suspension in PBS, and then 5 x 10^6 LLC cells were injected subcutaneously into C57/B6 male mice (Shanghai Slac Laboratory Animal Co. LTD, China) aged 8 weeks. Every group of mice consisted of 6 randomly assigned mice. When the tumor size was visible, the tumor size was measured once every three days until it reached 1000 mm3. REF000542 ICD-11: 2C25.0 Lung adenocarcinoma CELL00560; CELL10049 LLCs; BMDMs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell infiltration
unique01055 Concurrent loss-of-function mutations in STK11 and KEAP1 in lung adenocarcinoma (LUAD) are associated with aggressive tumor growth, resistance to available therapies, and early death. STK11/KEAP1 co-mutation results in significantly elevated expression of ferroptosis-protective genes, including SCD and AKR1C1/2/3, and resistance to pharmacologically induced ferroptosis. . . . . Suppressor . Mice in the + dox groups were fed a diet of doxycycline chow 3 days prior to injecting cells and throughout the remainder of the experiment. Mice in the -dox group were fed a diet of amoxicillin chow to avoid skin rash. Subcutaneous flank tumors were generated by injecting 5E6 A549 or 2E6 H460 confluent cells (n = 5 per group) suspended in 50% Matrigel into the right flank. REF000274 ICD-11: 2C25.0 Lung adenocarcinoma CELL00201; CELL00117; CELL00045; CELL00015 NCI-H358; NCI-H292; NCI-A549; NCI-H460 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01654 GEM and the ferroptosis inducer IKE synergistically inhibited the proliferation of lung adenocarcinoma (LUAD) cells. Targeting the FRG KIF20A can enhance ferroptosis and modulate the combination of GEM and IKE, which might serve as a therapeutic target in LUAD. . . . . Suppressor . . REF000859 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00066; CELL00201; CELL00317; CELL00236; CELL00056; CELL00045 293T; 16HBE; H358; PC9; HCC827; H1299; A549 Fatty acid metabolism (hsa01212) Cell ferroptosis
dupunique01771 GINS4 is a potential oncogene in lung adenocarcinoma (LUAD) that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD. . . . . Driver . The 4-wk-old female nude mice used in this study were purchased from Hunan SJA Laboratory Animal Co., Ltd (Changsha). Then, 2 x 106 GINS4 WT or KO A549 cells were injected s.c. into nude mice without matrigel. Tumor size was measured every 2 d with a caliper, and volume of tumor was calculated with the formula: L x W2 x 0.5, for L represents the longest diameter and W means the shortest diameter. Then, 2 x 106 p53 WT and KO A549 cells with shCon or shGINS4 overexpressing were injected s.c. into nude mice without matrigel. When tumors reached 60 to 100 mm3, p53 WT with shGINS4 mice were treated with ferrostatin-1 (S7243, Selleckchem) (20 mg/kg) in 2% DMSO, 50% PEG300, 5% Tween80, and 43% water by daily intraperitoneal injection. Tumors were measured three times a week. Mice were sacrificed and tumors were collected finally. Tumor tissue was made into a single-cell suspension for lipid ROS assay using Tumor Dissociation Kit (Miltenyi Biotec). REF001001 ICD-11: 2C25.0 Lung adenocarcinoma CELL00057; CELL00015; CELL00056; CELL00201; CELL00045 293T; H460; H1299; H358; A549 Cell adhesion molecules (hsa04514); Ferroptosis (hsa04216) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01675 Knockdown of KDM1A inhibited the level of c-Myc and increased the concentration of malondialdehyde (MDA) and irons in human lung cancer cells H1299 and A549. Downregulation of c-Myc could facilitate KDM1A knockdown-mediated ferroptosis. . . . . Suppressor . . REF000885 ICD-11: 2C25 Lung cancer CELL00056; CELL00045; CELL00249; CELL00201 H1299; A549; H157; H358 Ferroptosis (hsa04216) Cell ferroptosis
unique01726 Knockdown of LINC01572 significantly inhibited cell viability and induced ferroptosis in lung adenocarcinoma (LUAD) cell lines. . . . . Suppressor . . REF000948 ICD-11: 2C25.0 Lung adenocarcinoma CELL00045; CELL00196; CELL00085 A549; NCI-H2009; HBE Ferroptosis (hsa04216) Cell ferroptosis
unique01676 Knockdown of KDM1A inhibited the level of c-Myc and increased the concentration of malondialdehyde (MDA) and irons in human lung cancer. cells H1299 and A549. Downregulation of c-Myc could facilitate KDM1A knockdown-mediated ferroptosis. . . . . Suppressor . . REF000885 ICD-11: 2C25 Lung cancer CELL00056; CELL00045; CELL00249; CELL00201 H1299; A549; H157; H358 Ferroptosis (hsa04216) Cell ferroptosis
unique01702 LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes lung adenocarcinoma (LUAD) autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. . . . . Suppressor . The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Second Xiangya Hospital following the Guidelines of the Care and Use of Laboratory Animals issued by the Chinese Council on Animal Research. Briefly, female BALB/c nude mice at six weeks were obtained from Hunan SJA Laboratory Animal Co. Ltd. (Hunan, China) and kept in a specific pathogen-free environment. The mice were injected subcutaneously with 2 x 106 indicated cells into the left or right flank for 21 days (PC9) or 28 days (A549) post-implantation. At the end of the experiment, the tumours were dissected and weighed. REF000927 ICD-11: 2C25.0 Lung adenocarcinoma CELL00317; CELL00045 PC9; A549 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01703 LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes lung adenocarcinoma (LUAD) autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. . . . . Driver . The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Second Xiangya Hospital following the Guidelines of the Care and Use of Laboratory Animals issued by the Chinese Council on Animal Research. Briefly, female BALB/c nude mice at six weeks were obtained from Hunan SJA Laboratory Animal Co. Ltd. (Hunan, China) and kept in a specific pathogen-free environment. The mice were injected subcutaneously with 2 x 106 indicated cells into the left or right flank for 21 days (PC9) or 28 days (A549) post-implantation. At the end of the experiment, the tumours were dissected and weighed. REF000927 ICD-11: 2C25.0 Lung adenocarcinoma CELL00317; CELL00045 PC9; A549 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01704 LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes lung adenocarcinoma (LUAD) autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. . . . . Suppressor . The animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of Second Xiangya Hospital following the Guidelines of the Care and Use of Laboratory Animals issued by the Chinese Council on Animal Research. Briefly, female BALB/c nude mice at six weeks were obtained from Hunan SJA Laboratory Animal Co. Ltd. (Hunan, China) and kept in a specific pathogen-free environment. The mice were injected subcutaneously with 2 x 106 indicated cells into the left or right flank for 21 days (PC9) or 28 days (A549) post-implantation. At the end of the experiment, the tumours were dissected and weighed. REF000927 ICD-11: 2C25.0 Lung adenocarcinoma CELL00317; CELL00045 PC9; A549 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00841 LSH (HELLS) is involved in ferroptosis and is a potential therapeutic target in cancer because of its crucial role in ferroptosis. LSH functioned as an oncogene in lung cancer in vitro and in vivo. And LSH promotes the lipid metabolic genes, including SCD1 and FADS2. . . . . Suppressor . SCID Mice (Hunan SJA Laboratory Animal Co.Ltd.) were injected with A549 (1 x 106 cells/mouse) or H358 (2 x 106 cells/mouse) cells via mammary fat pad (10 mice/group). Mice with A549 or H358 cells were imaged from dorsal and ventral views every three days. REF000024 ICD-11: 2C25 Lung cancer CELL00342; CELL00085; CELL00045; CELL00201; CELL00204; CELL00317; CELL00486; CELL00309; CELL00057 MRC-5; HBE; A549; H358; H522; PC9; 95C; 95D; 293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00882 LSH induces ELAVL1 expression through the inactivation of p53 and ELAVL1 enhances LINC00336 levels through transcriptional regulation by interacting with LINC00336. Then, LINC00336 absorbs MIR6852 as a ceRNA, which increases the mRNA level of CBS, stimulating cell proliferation, colony formation, and tumor formation, and inhibiting ferroptosis in lung cancer. . . . . Suppressor . . REF000059 ICD-11: 2C25 Lung cancer CELL00201; CELL00317; CELL00045; CELL00306 H358; PC9; A549; SPC-A-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00883 LSH induces ELAVL1 expression through the inactivation of p53 and ELAVL1 enhances LINC00336 levels through transcriptional regulation by interacting with LINC00336. Then, LINC00336 absorbs MIR6852 as a ceRNA, which increases the mRNA level of CBS, stimulating cell proliferation, colony formation, and tumor formation, and inhibiting ferroptosis in lung cancer. . . . . Suppressor . . REF000059 ICD-11: 2C25 Lung cancer CELL00201; CELL00317; CELL00045; CELL00306 H358; PC9; A549; SPC-A-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00881 LSH induces ELAVL1 expression through the inactivation of p53 and ELAVL1 enhances LINC00336 levels through transcriptional regulation by interacting with LINC00336. Then, LINC00336 absorbs MIR6852 as a ceRNA, which increases the mRNA level of CBS, stimulating cell proliferation, colony formation, and tumor formation, and inhibiting ferroptosis in lung cancer. . . . . Driver . . REF000059 ICD-11: 2C25 Lung cancer CELL00201; CELL00317; CELL00045; CELL00306 H358; PC9; A549; SPC-A-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00884 LSH induces ELAVL1 expression through the inactivation of p53 and ELAVL1 enhances LINC00336 levels through transcriptional regulation by interacting with LINC00336. Then, LINC00336 absorbs MIR6852 as a ceRNA, which increases the mRNA level of CBS, stimulating cell proliferation, colony formation, and tumor formation, and inhibiting ferroptosis in lung cancer. . . . . Suppressor . . REF000059 ICD-11: 2C25 Lung cancer CELL00201; CELL00317; CELL00045; CELL00306 H358; PC9; A549; SPC-A-1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
dupunique00859 P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA-G3BP1 interaction displaced p53 from a G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to cell-cycle arrest, apoptosis, and ferroptosis in lung cancer cell lines. . . . . Driver . SCID mice (Hunan SJA Laboratory Animal Co. Ltd.) were injected with the indicated cells in the mammary fat pad (10 mice/group). Injected mice were imaged from both the dorsal and ventral sides every three days. REF000038 ICD-11: 2C25 Lung cancer CELL00045; CELL00306; CELL00204; CELL00085; CELL00056; CELL00342; CELL00201; CELL00317; CELL00486; CELL00309 A549; SPCA1; H522; HBE; H1299; MRC-5; H358; PC9; 95C; 95D Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01105 The expression level of miR-101-3p negatively correlated with clinical tumour size and TNM stage. miR-101-3p restores ferroptosis in lung cancer cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. . . . . Driver . BALB/c mice (male, 6 weeks old, 20-22 g) were obtained from Vital River Laboratories (Beijing, China). Immunodeficient mice were randomly divided into groups (n = 6 per group). A549 cells (1 x 106) were injected subcutaneously into the dorsal left flank of nude mice. In each group, mice (20-25 g) were administered 100 uL of the nanomedicine working solution through the tail vein, once every 3 days. REF000349 ICD-11: 2C25 Lung cancer CELL00045; CELL10035; CELL00015; CELL00262; CELL00306; CELL00317 A549; L78; NCI-H460; GLC-82; SPC-A1; PC9 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01106 The expression level of miR-101-3p negatively correlated with clinical tumour size and TNM stage. miR-101-3p restores ferroptosis in lung cancer cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. . . . . Suppressor . BALB/c mice (male, 6 weeks old, 20-22 g) were obtained from Vital River Laboratories (Beijing, China). Immunodeficient mice were randomly divided into groups (n = 6 per group). A549 cells (1 x 106) were injected subcutaneously into the dorsal left flank of nude mice. In each group, mice (20-25 g) were administered 100 uL of the nanomedicine working solution through the tail vein, once every 3 days. REF000349 ICD-11: 2C25 Lung cancer CELL00045; CELL10035; CELL00015; CELL00262; CELL00306; CELL00317 A549; L78; NCI-H460; GLC-82; SPC-A1; PC9 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01309 The expression of AKR1C1 was upregulated in non-small cell lung cancer (NSCLC) cell lines, and silencing AKR1C1 can inhibit the proliferation and migration of NSCLC cells and promote the occurrence of ferroptosis. . . . . Suppressor . . REF000561 ICD-11: 2C25.Y Non-small cell lung cancer CELL00045; CELL00317; CELL00195; CELL00076 A549; PC-9; H1975; BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01019 The main upstream kinase responsible for the activation of AMPK in response to energy stress is LKB1 (STK11), LKB1 is a negative regulator of ferroptosis and LKB1 status might be useful as a biomarker to predict non-small cell lung carcinoma responsiveness to the induction of ferroptosis. . . . . Suppressor . . REF000227 ICD-11: 2C25.Y Non-small cell lung cancer CELL10119 MEF Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); AMPK signaling pathway (hsa04152) Cell ferroptosis
unique01461 The study found GSEC, CISD1, ATP5MC3, and PGD to be upregulated, with miRNA-101-3p downregulated, in the setting of lung adenocarcinoma (LUAD). Immunohistochemical analysis revealed CISD1, ATP5MC3, and PGD overexpression in LUAD tissue samples; CISD1 knockdown was noted to significantly inhibit LUAD proliferation and migration. . . . . Driver . . REF000693 ICD-11: 2C25.0 Lung adenocarcinoma CELL00076; CELL00045; CELL00195 BEAS-2B; A549; H1975 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell infiltration
unique00284 Ringer's lactate (PAL) induces selective ferroptosis of malignant mesothelioma (MM) cells. PAL-induced ferroptosis accompanied autophagic process in the early phase, as demonstrated by an increase in essential amino acids, LC3B-II, p62 and LAMP1, transforming into the later phase with boosted lipid peroxidation. Inducer . . . . . . REF000399 ICD-11: 2C26 Malignant mesothelioma CELL00456; CELL00501; CELL00513; CELL00095 Y-Meso-8A; NCIH290; LP9; HT1080 Ferroptosis (hsa04216); Autophagy (hsa04140); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell autophagy
unique01555 ATF3-induced miR-21-3p upregulation contributed to the efficacy of anti-PD-1 immunotherapy by facilitating melanoma cell ferroptosis via the suppression of the novel target TXNRD1 and lipid peroxidation. Nanoparticle delivery of miR-21-3p could sensitize melanoma cells to anti-PD-1 immunotherapy by facilitating ferroptosis. . . . . Driver . In liproxstatin-1 rescue experiment, 5 x 105 B16F10 cells were subcutaneously injected into the right flank of C57BL/6 mice. When the tumor grows to 50 mm3, 100 ug anti-PD-1 antibody (Bio X Cell, USA), 30 mg/kg liproxstatin-1 (MedChemExpress, USA) or both were administered intraperitoneally to each mouse. Anti-PD-1 antibody was administered every 3 days and liproxstatin-1 was administered every day. REF000764 ICD-11: 2C30 Melanoma CELL00313; CELL00154; CELL00069; CELL00099; CELL00007 WM793B; A2058; A375; Hs294T; B16F10 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00262 Arachidonic acid from tumor and TME induce tumor-infiltrating CD8T-cell ferroptosis through CD36. Targeting CD36 and ferroptosis may be an effective strategy to improve the antitumor efficacy of T cell-based immunotherapy in melanoma cell line. Inducer . . . . . Mice (4-5/group) were injected s.c. in the right back flank with 1 x 106 B16 tumor cells. After 7 to 14 days, tumors formed and were collected for flow cytometry analysis. In some mice, tumor growth was monitored till the end point, and CD8-depleting antibodies (200 ug per mice) were injected one day before tumor injection, followed by 4 consecutive injections every 3 days. In B16 melanoma lung metastatic model, mice were injected i.v. with 2 x 105 B16 cells. REF000354 ICD-11: 2C30 Melanoma CELL00566 B16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00089 Nitroprusside induces melanoma ferroptosis with serum supplementation and prolongs survival under serum depletion or hypoxia. Inducer . . . . . . REF000142 ICD-11: 2C30 Melanoma CELL00566 B16 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); MAPK signaling pathway (hsa04010) Cell ferroptosis; Cell proliferation
unique01553 ATF3-induced miR-21-3p upregulation contributed to the efficacy of anti-PD-1 immunotherapy by facilitating melanoma cell ferroptosis via the suppression of the novel target TXNRD1 and lipid peroxidation. Nanoparticle delivery of miR-21-3p could sensitize melanoma cells to anti-PD-1 immunotherapy by facilitating ferroptosis. . . . . Driver . In liproxstatin-1 rescue experiment, 5 x 105 B16F10 cells were subcutaneously injected into the right flank of C57BL/6 mice. When the tumor grows to 50 mm3, 100 ug anti-PD-1 antibody (Bio X Cell, USA), 30 mg/kg liproxstatin-1 (MedChemExpress, USA) or both were administered intraperitoneally to each mouse. Anti-PD-1 antibody was administered every 3 days and liproxstatin-1 was administered every day. REF000764 ICD-11: 2C30 Melanoma CELL00313; CELL00154; CELL00069; CELL00099; CELL00007 WM793B; A2058; A375; Hs294T; B16F10 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01554 ATF3-induced miR-21-3p upregulation contributed to the efficacy of anti-PD-1 immunotherapy by facilitating melanoma cell ferroptosis via the suppression of the novel target TXNRD1 and lipid peroxidation. Nanoparticle delivery of miR-21-3p could sensitize melanoma cells to anti-PD-1 immunotherapy by facilitating ferroptosis. . . . . Suppressor . In liproxstatin-1 rescue experiment, 5 x 105 B16F10 cells were subcutaneously injected into the right flank of C57BL/6 mice. When the tumor grows to 50 mm3, 100 ug anti-PD-1 antibody (Bio X Cell, USA), 30 mg/kg liproxstatin-1 (MedChemExpress, USA) or both were administered intraperitoneally to each mouse. Anti-PD-1 antibody was administered every 3 days and liproxstatin-1 was administered every day. REF000764 ICD-11: 2C30 Melanoma CELL00313; CELL00154; CELL00069; CELL00099; CELL00007 WM793B; A2058; A375; Hs294T; B16F10 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01470 The GO and KEGG analysis suggested that the underlying mechanism of PLA2G6 in cutaneous malignant melanoma (CMM) might be associated with the ferroptosis pathway, and ferroptosis-related proteins were validated to be differentially expressed in PLA2G6 knockdown SK-MEL-28 and M14 cells. Together, PLA2G6 knockdown significantly inhibited cell proliferation, metastasis, and promoted apoptosis in melanoma. . . . . Suppressor . A total of 10 female BALB/c nude mice (4-6 weeks old) were supplied by Shanghai SLAC Laboratory Animal Co., Ltd (Shanghai, China). The nude mice were randomly divided into different treatment groups with five mice each, and maintained in a pathogen-free animal facility, followed by subcutaneously injection with 1 x 107 cells/mL M14 cells in 100 uL PBS on the right side to establish a subcutaneous xenograft model. REF000698 ICD-11: 2C30 Melanoma CELL00609; CELL00191; CELL00069; CELL00444 SK-MEL-28; M14; A375; A875 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion; Cell metastasis
unique00209 The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal melanoma cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in CCRF-CEM cellsviacaspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis. Inducer . . . . . . REF000272 ICD-11: 2C30 Melanoma CELL00542; CELL00007; CELL00154; CELL10080; CELL00499; CELL00330; CELL00609; CELL00502 B16F1; B16F10; A2058; SK-Mel 505; MaMel-80a; MV3; SkMel-28; Mel-2A Apoptosis (hsa04210); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique00108 Artesunate predominantly induces ferroptosis in MCPyV-positive merkel cell carcinoma (MCC) cells since known ferroptosis-inhibitors like DFO, BAF-A1, Fer-1 and -mercaptoethanol reduced artesunate-induced death. Rosiglitazone (Rosi), an inhibitor of the Acyl-CoA synthetase long-chain family member 4 (ACSL4). Indeed, Rosi exerted a protective effect on all three tested artesunate-treated MCC cell lines. Inducer . . . . . Five-week-old female NOD.CB17/Prkdcscid mice (Charles River) were used for the xenotransplantation experiments. They were housed under specific pathogen-free conditions. Each mouse was injected subcutaneously with a suspension of 5 x 106 MKL-1 or WaGa tumor cells mixed with an equal volume of Matrigel (Corning) in a total volume of 100 uL. The tumor size was measured daily using a vernier calipers. REF000161 ICD-11: 2C34 Merkel cell carcinoma CELL00413; CELL00509; CELL00194; CELL00514; CELL00326 MKL-1; MKL-2; MS-1; WaGa; PeTa Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01178 SCD1 and FABP4 were also found upregulated in recurrent human breast cancer samples and correlated with worse prognosis of cancer patients with different types of tumors. Mechanistically, SCD1 leads to fatty acid (FA) desaturation and FABP4 derived from TEM enhances lipid droplet (LD) in cancer cells, which cooperatively protect from oxidative stress-induced ferroptosis. . . . . . Suppressor For treatment with RSL3 (20 mg/kg), drug was administered in mice bearing LLC tumors by i.p. injection every other day for 2 weeks. For cisplatin, BALB/c mice bearing 4T1 tumors (50-100 mm3) were administered by i.p. injection of vehicle (0.7% DMSO in PBS) or cisplatin (7 mg/kg/week) for 3 weeks. REF000415 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00560; CELL10037 MDA-MB-231; LLCs; HUVECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01026 BRD4 transcript and protein levels are highly enriched in triple-negative breast cancer tumors and cell lines. Cotargeting of BET (BRD2, BRD3, BRD4, BRDT) and the proteasome applied at low doses could be a promising therapeutic approach for TNBC. . . . . Suppressor . For mouse xenograft models, MDA-MB-231 cells (2 x 106 per mouse) expressing green fluorescent protein (GFP) luciferase were implanted bilaterally into the fat pads of the fourth inguinal mammary gland of 6-week-old female athymic nude-Foxn1nu mice. Twenty-three days later, mice were randomized into four groups (n = 10 mice per group) and treated with the following: (i) vehicle; (ii) OTX015, daily through oral gavage (25 mg/kg); OTX015 (100 mg/ml stock in DMSO) was diluted in vehicle solution containing 2% DMSO, 30% polyethylene glycol (PEG)300, and 5% Tween 80; (iii) SB225022, which was intraperitoneally administered 5 days a week, at 5 mg/kg prepared in PBS; or (iv) OTX015 + SB225022 combination. REF000232 ICD-11: 2C60 Triple-negative breast cancer CELL00141; CELL00057; CELL00171; CELL00112; CELL00165; CELL00086; CELL00173; CELL00171; CELL00005; CELL00156; CELL00460; CELL00010 MCF10A; HEK293T; HCC38; MDA-MB-468; HCC1143; HCC1937; HCC70; HCC38; MDA-MB-231; BT549; SUM159; Hs578T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00941 Prominin2 (PROM2) facilitates ferroptosis resistance in mammary epithelial and breast cancer cells. Mechanistically, prominin2 promotes the formation of ferritin-containing multivesicular bodies (MVBs) and exosomes that transport iron out of the cell, inhibiting ferroptosis. . . . . Suppressor . . REF000111 ICD-11: 2C60-2C65 Breast cancer CELL00141; CELL00010; CELL00005 MCF10A; Hs578T; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01828 WTAP knockdown promoted ferroptosis to suppress triple-negative breast cancer (TNBC) cell malignant behaviors, which were abrogated by NUPR1 overexpression. WTAP upregulated LCN2 by regulation of NUPR1 m6A modification, thereby suppressing ferroptosis to contribute to accelerate TNBC progression. . . . . Suppressor . . REF001052 ICD-11: 2C60 Triple-negative breast cancer CELL00002; CELL00005; CELL00214; CELL00135; CELL00156; CELL00141 MCF7; MDA-MB-231; ZR-75-30; T47D; BT549; MCF-10 A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00467 Herceptin induced injury, oxidative stress, mitochondrial dysfunction and ferroptosis in H9c2 cells, which could be attenuated by Fer-1. These findings provided insights into the pathogenic mechanism that underlie Herceptin-induced cardiomyopathy, which potentially provides a novel therapeutic target for the prevention of cardiotoxicity in HER2 breast cancer treatment. Inducer . . . . . . REF000617 ICD-11: 2C60 HER2 positivebreast cancer CELL00030 H9C2 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00042 Neratinib promotes a non-apoptotic form of cell death termed ferroptosis. Importantly, metastasis assays demonstrate that neratinib potently inhibits breast cancer growth and metastasis, including to the brain, and prolongs survival, particularly when used as a neoadjuvant therapy. Inducer . . . . . Female BALB/C mice (5/box) were maintained in a specific pathogen-free environment. For initial characterisation of metastatic spread, TBCP-1 cells (5 x 105) were injected into the left cardiac ventricle of 6-8-week-old female BALB/C mice. The mice were monitored daily and sacrificed after 3 weeks or earlier if signs of metastases became apparent (weight loss > 10%, ruffled fur, lethargy, rapid breathing). REF000082 ICD-11: 2C60-2C65 Breast cancer CELL00580; CELL00583; CELL00540; CELL00002; CELL00078; CELL00003; CELL00005 67NR; 4T1.2; 4T1Br4; TBCP-1; MCF-7; BT474; SKBR3; MDA-MB-231 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell metastasis
unique00012 Piperlongumine (PL) is a natural product with cytotoxic properties restricted to cancer cells by significantly increasing intracellular reactive oxygen species (ROS) levels. The study demonstrated that PL induced cancer cell death through, at least in part, the induction of ferroptosis. And the triple combined treatment with PL, CNA and SSZ is highly effective against pancreatic cancer. Inducer . . . . . . REF000035 ICD-11: 2C60-2C65 Breast cancer CELL00013; CELL00120; CELL00160; CELL00008 MIAPaCa-2; PANC-1; CFPAC-1; BxPC-3; Mouse embryonic fibroblasts (MEFs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00842 A synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast cancer stem cells (CSCs) in vitro and in vivo, by accumulating and sequestering iron in lysosomes. Inducer . . . . . MCF-7 cell cultures were collected, enzymatically dissociated, washed with PBS, and re-suspended in a PBS/Matrigel mixture (1:1 v/v). The mixture (0.1 mL) was then implanted in the mammary fat pad of 5-week-old female AthymicNude-Fox1nu mice bilaterally (Harlan, France). Mice received estradiol supplementation (0.4 mg/kg) the same day and 7 days from cell injection, and were observed and palpated for tumor appearance. Mice were treated with AM5 (1 mg/kg body weight/day) by means of intraperitoneal injections every 5 working days of the week. REF000025 ICD-11: 2C60-2C65 Breast cancer CELL00512; CELL00055; CELL00002 HMLER; iCSCL-10A2; U2OS; MCF-7 Ferroptosis (hsa04216) Cell ferroptosis
unique00022 As ferroptocide induces a regulated, non-apoptotic mode of cell death, this compound (and possibly other pro-ferroptotic agents) have the potential to synergize with the immune system for the treatment of breast cancer. Inducer . . . . . . REF000066 ICD-11: 2C60-2C65 Breast cancer CELL00263; CELL00087; CELL00540; CELL00045; CELL00141; CELL00260 ES-2; HCT116; 4T1; A549; MCF10A; HFF-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01025 BRD4 transcript and protein levels are highly enriched in triple-negative breast cancer tumors and cell lines. Cotargeting of BET ( BRD2, BRD3, BRD4, BRDT) and the proteasome applied at low doses could be a promising therapeutic approach for TNBC. . . . . Suppressor . For mouse xenograft models, MDA-MB-231 cells (2 x 106 per mouse) expressing green fluorescent protein (GFP) luciferase were implanted bilaterally into the fat pads of the fourth inguinal mammary gland of 6-week-old female athymic nude-Foxn1nu mice. Twenty-three days later, mice were randomized into four groups (n = 10 mice per group) and treated with the following: (i) vehicle; (ii) OTX015, daily through oral gavage (25 mg/kg); OTX015 (100 mg/ml stock in DMSO) was diluted in vehicle solution containing 2% DMSO, 30% polyethylene glycol (PEG)300, and 5% Tween 80; (iii) SB225022, which was intraperitoneally administered 5 days a week, at 5 mg/kg prepared in PBS; or (iv) OTX015 + SB225022 combination. REF000232 ICD-11: 2C60 Triple-negative breast cancer CELL00141; CELL00057; CELL00171; CELL00112; CELL00165; CELL00086; CELL00173; CELL00171; CELL00005; CELL00156; CELL00460; CELL00010 MCF10A; HEK293T; HCC38; MDA-MB-468; HCC1143; HCC1937; HCC70; HCC38; MDA-MB-231; BT549; SUM159; Hs578T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01024 BRD4 transcript and protein levels are highly enriched in triple-negative breast cancer tumors and cell lines. Cotargeting of BET (BRD2, BRD3, BRD4, BRDT) and the proteasome applied at low doses could be a promising therapeutic approach for TNBC. . . . . Suppressor . For mouse xenograft models, MDA-MB-231 cells (2 x 106 per mouse) expressing green fluorescent protein (GFP) luciferase were implanted bilaterally into the fat pads of the fourth inguinal mammary gland of 6-week-old female athymic nude-Foxn1nu mice. Twenty-three days later, mice were randomized into four groups (n = 10 mice per group) and treated with the following: (i) vehicle; (ii) OTX015, daily through oral gavage (25 mg/kg); OTX015 (100 mg/ml stock in DMSO) was diluted in vehicle solution containing 2% DMSO, 30% polyethylene glycol (PEG)300, and 5% Tween 80; (iii) SB225022, which was intraperitoneally administered 5 days a week, at 5 mg/kg prepared in PBS; or (iv) OTX015 + SB225022 combination. REF000232 ICD-11: 2C60 Triple-negative breast cancer CELL00141; CELL00057; CELL00171; CELL00112; CELL00165; CELL00086; CELL00173; CELL00171; CELL00005; CELL00156; CELL00460; CELL00010 MCF10A; HEK293T; HCC38; MDA-MB-468; HCC1143; HCC1937; HCC70; HCC38; MDA-MB-231; BT549; SUM159; Hs578T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01023 BRD4 transcript and protein levels are highly enriched in triple-negative breast cancer tumors and cell lines. Cotargeting of BET (BRD2, BRD3, BRD4, B RDT) and the proteasome applied at low doses could be a promising therapeutic approach for TNBC. . . . . Suppressor . For mouse xenograft models, MDA-MB-231 cells (2 x 106 per mouse) expressing green fluorescent protein (GFP) luciferase were implanted bilaterally into the fat pads of the fourth inguinal mammary gland of 6-week-old female athymic nude-Foxn1nu mice. Twenty-three days later, mice were randomized into four groups (n = 10 mice per group) and treated with the following: (i) vehicle; (ii) OTX015, daily through oral gavage (25 mg/kg); OTX015 (100 mg/ml stock in DMSO) was diluted in vehicle solution containing 2% DMSO, 30% polyethylene glycol (PEG)300, and 5% Tween 80; (iii) SB225022, which was intraperitoneally administered 5 days a week, at 5 mg/kg prepared in PBS; or (iv) OTX015 + SB225022 combination. REF000232 ICD-11: 2C60 Triple-negative breast cancer CELL00141; CELL00057; CELL00171; CELL00112; CELL00165; CELL00086; CELL00173; CELL00171; CELL00005; CELL00156; CELL00460; CELL00010 MCF10A; HEK293T; HCC38; MDA-MB-468; HCC1143; HCC1937; HCC70; HCC38; MDA-MB-231; BT549; SUM159; Hs578T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01177 SCD1 and FABP4 were also found upregulated in recurrent human breast cancer samples and correlated with worse prognosis of cancer patients with different types of tumors. Mechanistically, SCD1 leads to fatty acid (FA) desaturation and FABP4 derived from TEM enhances lipid droplet (LD) in cancer cells, which cooperatively protect from oxidative stress-induced ferroptosis. . . . . Suppressor . For treatment with RSL3 (20 mg/kg), drug was administered in mice bearing LLC tumors by i.p. injection every other day for 2 weeks. For cisplatin, BALB/c mice bearing 4T1 tumors (50-100 mm3) were administered by i.p. injection of vehicle (0.7% DMSO in PBS) or cisplatin (7 mg/kg/week) for 3 weeks. REF000415 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00560; CELL10037 MDA-MB-231; LLCs; HUVECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01372 The LINC00665-miR-410-3p axis was identified as the most potential upstream ncRNA-related pathway of EMC2 in breast cancer. EMC2 levels were significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. . . . . Driver . . REF000625 ICD-11: 2C60-2C65 Breast cancer CELL00141; CELL00002; CELL00005 MCF10A; MCF-7; MDA-MB-231 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique00008 The combination of siramesine, a lysosome disruptor, and lapatinib, a dual tyrosine kinase inhibitor, has been shown to synergistically induce cell death in breast cancer cells mediated by ferroptosis. Siramesine and lapatinib initially induced ferroptosis but changes to an autophagy induced cell death after 24 hours. Inducer . . . . . . REF000022 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00003 MDA MB-231; SKBR3 Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00009 The combination of siramesine, a lysosome disruptor, and lapatinib, a dual tyrosine kinase inhibitor, has been shown to synergistically induce cell death in breast cancer cells mediated by ferroptosis. Siramesine and lapatinib initially induced ferroptosis but changes to an autophagy induced cell death after 24 hours. Inducer . . . . . . REF000022 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00003 MDA MB-231; SKBR3 Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01859 The combined effects of vorinostat with salazosulfapyridine (SASP) depend on the accumulation of ROS caused by a decrease in intracellular GSH levels in breast adenocarcinoma, possibly due to SASP-mediated inhibition of xCT. xCT (coded by the SLC7A11 gene), a light chain subunit of the glutamate-cystine antiporter system Xc(-). Inducer . . . . . . REF000158 ICD-11: 2C60 Breast adenocarcinoma CELL00005; CELL00087 MDA-MB-231; HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01107 The depletion of circRHOT1 was able to repress the proliferation and induce the apoptosis of breast cancer cells. CircRHOT1 knockdown could remarkably inhibit the invasion and migration in the breast cancer cells. Mechanically, circRHOT1 contributed to malignant progression and attenuated ferroptosis in breast cancer by the miR-106a-5p/STAT3 axis. . . . . Suppressor . The effect of levobupivacaine on tumor growth of breast cancer in vivo was assessed in the Balb/c nude mice (male, 4-week-old) (n = 5). About 1 x 107 cells MDA-MB-231 cells transfected with control shRNA or circRHOT1 shRNA were subcutaneously injected into the mice. After 5 days of injection, we measured tumor growth every 5 days. We sacrificed the mice after 30 days of injection, and tumors were scaled. REF000352 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00135 MDA-MB-231; T47D Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01109 The depletion of circRHOT1 was able to repress the proliferation and induce the apoptosis of breast cancer cells. CircRHOT1 knockdown could remarkably inhibit the invasion and migration in the breast cancer cells. Mechanically, circRHOT1 contributed to malignant progression and attenuated ferroptosis in breast cancer by the miR-106a-5p/ STAT3 axis. . . . . Suppressor . The effect of levobupivacaine on tumor growth of breast cancer in vivo was assessed in the Balb/c nude mice (male, 4-week-old) (n = 5). About 1 x 107 cells MDA-MB-231 cells transfected with control shRNA or circRHOT1 shRNA were subcutaneously injected into the mice. After 5 days of injection, we measured tumor growth every 5 days. We sacrificed the mice after 30 days of injection, and tumors were scaled. REF000352 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00135 MDA-MB-231; T47D Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique01108 The depletion of circRHOT1 was able to repress the proliferation and induce the apoptosis of breast cancer cells. CircRHOT1 knockdown could remarkably inhibit the invasion and migration in the breast cancer cells. Mechanically, circRHOT1 contributed to malignant progression and attenuated ferroptosis in breast cancer by the miR-106a-5p/STAT3 axis. . . . . Driver . The effect of levobupivacaine on tumor growth of breast cancer in vivo was assessed in the Balb/c nude mice (male, 4-week-old) (n = 5). About 1 x 107 cells MDA-MB-231 cells transfected with control shRNA or circRHOT1 shRNA were subcutaneously injected into the mice. After 5 days of injection, we measured tumor growth every 5 days. We sacrificed the mice after 30 days of injection, and tumors were scaled. REF000352 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00135 MDA-MB-231; T47D Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation; Cell migration; Cell invasion
unique00261 The FDA-approved drug bazedoxifene acts as a potent radical trapping antioxidant inhibitor of ferroptosis both in vitro and in vivo. Bazedoxifene potently suppressed ferroptosis in MDA-MB-231, E0771, and 4T1 breast cancer cell lines which do not express the estrogen receptor. Suppressor . . . . . N2 Bristol (wild-type) nematodes were maintained on nematode growth media (NGM) plates seeded with bacteria (E. coliOP50) at 20. Experiments with dihomo--linolenic acid (DGLA) were performed using NGM plates formulated with 0.1% Tergitol NP40 (Sigma Chemicals) and 0.125 mM DGLA sodium salt (NuChek Prep, Inc.) or Tergitol alone (vehicle). Dry plates were seeded with OP50 and then three days later ferrostatin-1 or bazedoxifene were dissolved into the plates at a final concentration of 150 uM and allowed to dry for 30 min, before ~50 synchronized L1 larvae were transferred to each plate. Sterility was scored 72-96 h later, as determined by light microscopic examination of uterine embryos. REF000351 ICD-11: 2C60-2C65 Breast cancer CELL00095; CELL00055; CELL00005; CELL00057; CELL00056; CELL00045; CELL00137; CELL00081; CELL00069; CELL00540; CELL00582 HT-1080; U-2 OS; MDA-MB-231; HEK293T; NCI-H1299; A549; T98G; Caki-1; A375; 4T1; E0771 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01373 The LINC00665- miR-410-3p axis was identified as the most potential upstream ncRNA-related pathway of EMC2 in breast cancer. EMC2 levels were significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. . . . . Suppressor . . REF000625 ICD-11: 2C60-2C65 Breast cancer CELL00141; CELL00002; CELL00005 MCF10A; MCF-7; MDA-MB-231 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique01371 The LINC00665-miR-410-3p axis was identified as the most potential upstream ncRNA-related pathway of EMC2 in breast cancer. EMC2 levels were significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. . . . . Driver . . REF000625 ICD-11: 2C60-2C65 Breast cancer CELL00141; CELL00002; CELL00005 MCF10A; MCF-7; MDA-MB-231 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique00211 The prominent cytotoxic potential of soyauxinium chloride (SCHL) on a panel of 18 human and animal cancer cell lines, including MDR phenotypes. This investigated indoloquinazoline alkaloid induced apoptosis in CCRF-CEM cellsviacaspases activation, MMP alteration and increase of ROS production, and caused ferroptosis and necroptosis in breast cancer. Inducer . . . . . . REF000272 ICD-11: 2C60-2C65 Breast cancer CELL00044; CELL00005 MGEGFR; MDA-MB-231-pcDNA3 Apoptosis (hsa04210); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01827 WTAP knockdown promoted ferroptosis to suppress triple-negative breast cancer (TNBC) cell malignant behaviors, which were abrogated by NUPR1 overexpression. WTAP upregulated LCN2 by regulation of NUPR1 m6A modification, thereby suppressing ferroptosis to contribute to accelerate TNBC progression. . . . . Suppressor . . REF001052 ICD-11: 2C60 Triple-negative breast cancer CELL00002; CELL00005; CELL00214; CELL00135; CELL00156; CELL00141 MCF7; MDA-MB-231; ZR-75-30; T47D; BT549; MCF-10 A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01829 WTAP knockdown promoted ferroptosis to suppress triple-negative breast cancer (TNBC) cell malignant behaviors, which were abrogated by NUPR1 overexpression. WTAP upregulated LCN2 by regulation of NUPR1 m6A modification, thereby suppressing ferroptosis to contribute to accelerate TNBC progression. . . . . Suppressor . . REF001052 ICD-11: 2C60 Triple-negative breast cancer CELL00002; CELL00005; CELL00214; CELL00135; CELL00156; CELL00141 MCF7; MDA-MB-231; ZR-75-30; T47D; BT549; MCF-10 A Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01090 Zinc is also essential for ferroptosis in breast cancer and renal cancer cells. The study identified SLC39A7, encoding ZIP7 that controls zinc transport from endoplasmic reticulum (ER) to cytosol, as a novel genetic determinant of ferroptosis. . . . . Driver . . REF000329 ICD-11: 2C60-2C65 Breast cancer CELL00005; CELL00095; CELL00121 MDA-MB-231; HT-1080; RCC4 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01284 GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. . . . . Suppressor . . REF000537 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00608; CELL00430 SKOV3; OVCAR-3; OVISE Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00867 In high-OXPHOS tumors, chronic oxidative stress promotes aggregation of PML-nuclear bodies, resulting in activation of the transcriptional co-activator PGC-1. Active PGC-1 increases synthesis of electron transport chain complexes, thereby promoting mitochondrial respiration. The data establish a stress-mediated PML-PGC-1-dependent mechanism that promotes OXPHOS metabolism and chemosensitivity in ovarian cancer. . . . . Suppressor . Tumor fragments from PDX models were grafted into the interscapular fat pad of 6-week-old female Swiss nude mice under avertin anesthesia. When tumors reached a volume of 60-200 mm3, mice were blindly assigned to control (vehicle, NaCl 0.9%) or treated groups (at least n = 9 per condition). Mice were treated intraperitoneally by carboplatin (ACCORD) at 66 mg / kg every three weeks and paclitaxel (KABI) at 12 mg / kg once a week. REF000049 ICD-11: 2C73 Ovarian cancer CELL00128; CELL00437; CELL00079; CELL00415; CELL00248; CELL00414; CELL00211; CELL00385; CELL00183; CELL00429; CELL00210; CELL00403; CELL00410 SKOV3; OV90; CAOV3; OV7; COV504; OV56; OVCAR8; OC314; KURAMOCHI; OVSAHO; OVCAR4; FUOV1; COV318 Ferroptosis (hsa04216); Gluconeogenesis (hsa00010); Oxidative phosphorylation (hsa00190) Cell ferroptosis
unique01663 Two molecular subtypes were classified by BRDs for ovarian serous cystadenocarcinoma (OSC), which were significantly correlated with stemness features, m6A methylation, ferroptosis, drug sensitivity, and immune infiltration. BRDs are potential targets and biomarkers for OSC patients, especially BRPF1. . . . . Driver . . REF000868 ICD-11: 2C73 Ovarian serous cystadenocarcinoma CELL00128 SKOV3 Ferroptosis (hsa04216); Gluconeogenesis (hsa00010); Wnt signaling pathway (hsa04310) Cell ferroptosis; Cell proliferation
unique01319 Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer. . . . . Suppressor . Four-week-old male nude mice (N = 72) were purchased from SJA Laboratory Animal Co., Ltd. (Hunan, China), and raised in the standard animal facility room. Cervical cancer cells were infected with the control vector, Cdc25A, Cdc25A + sh-NC, and Cdc25A + sh-ErbB2 lentiviruses for 24 h and then unilateral subaxillary subcutaneously injected into nude mice (1 x 107 cells per mouse) to induce tumours. REF000573 ICD-11: 2C77.Z Cervical cancer CELL00050; CELL00157 SiHa; CaSki Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01850 Gallic acid (GA) could induce coexistence of multiple types of cell death pathways, including apoptosis characterized by mitochondrial cytochromecrelease and caspase-3 activation, ferroptosis characterized by lipid peroxidation, and necroptosis characterized by the loss of plasma membrane integrity in endocervical adenocarcinoma condition. Inducer . . . . . . REF000085 ICD-11: 2C77 Endocervical adenocarcinoma CELL00049; CELL00042; CELL00203 HeLa; SH-SY5Y; H446 Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01320 Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer. . . . . Suppressor . Four-week-old male nude mice (N = 72) were purchased from SJA Laboratory Animal Co., Ltd. (Hunan, China), and raised in the standard animal facility room. Cervical cancer cells were infected with the control vector, Cdc25A, Cdc25A + sh-NC, and Cdc25A + sh-ErbB2 lentiviruses for 24 h and then unilateral subaxillary subcutaneously injected into nude mice (1 x 107 cells per mouse) to induce tumours. REF000573 ICD-11: 2C77.Z Cervical cancer CELL00050; CELL00157 SiHa; CaSki Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01000 DECR1 knockdown selectively inhibited -oxidation of PUFAs, inhibited proliferation and migration of prostate cancer cells, including treatment resistant lines, and suppressed tumor cell proliferation and metastasis in mouse xenograft models. . . . . Suppressor . LNCaP cells (5 x 106 cells in 50 uL 10% FBS/RPMI 1640 medium) were co-injected subcutaneously with 50 uL Matrigel in 6-week-old NOD Scid Gamma male mice (Bioresource Facility, Austin Health, Heidelberg, Australia). When tumors reached~200 mm3, mice were randomized in different therapy groups. REF000200 ICD-11: 2C82 Prostate cancer CELL00446; CELL00405; CELL00108; CELL00408; CELL00150; CELL00526 PNT1; PNT2; LNCaP; VCaP; 22RV1; V16D; MR49F Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Citrate cycle (hsa00020) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique00981 DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises castration-resistant prostate cancer (CRPC) cells to ferroptosis. . . . . Suppressor . 20 x 106 cells/mouse were suspended in serum-free medium and mixed with Matrigel (Corning, NY, USA) in a 1:1 ratio. 50 ul of cell suspension were injected orthotopically into the anterior prostate lobe of CD1-nude mice (Charles River Laboratories, Wilmington, MA, USA). Orchidectomy was performed at the time of injection. Tumours were allowed to grow for ~6 weeks after injection and tumour growth was monitored weekly using a Vevo3100 ultrasound imaging system (Fujifilm Visualsonics, The Netherlands). REF000177 ICD-11: 2C82 Castration-resistant prostate cancer CELL00108; CELL00283; CELL00441 LNCaP; C4-2; CWR22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01179 VCP functions as a molecular switch for mitochondrial activity, and this switch is turned off by its relocalization and aggregation when PC3 prostate cancer cells are faced with starvation, consequently lowering mitochondrial activity, ROS production, and the risk of ferroptosis. . . . . Suppressor . . REF000416 ICD-11: 2C82 Prostate cancer CELL00051 PC3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00397 Testosterone induces two parallel autophagy-mediated processes, ferritinophagy and nucleophagy, which then activate nucleic acid sensors to drive immune signaling pathways in prostate cancer. Inducer . . . . . Adult athymic nude mice were inoculated subcutaneously in the flank with the LNCaP human prostate cancer cell lines in 200 uL of Matrigel. Mice were divided into two groups, and the treatment group was implanted with 2 one cm long silastic implants filled with testosterone as described previously. Tumors were harvested 2- and 4-days post-treatment and fixed in 10% buffered formalin and processed for IHC and H&E staining. REF000539 ICD-11: 2C82 Prostate cancer CELL00108; CELL00445; CELL00057; CELL00404; CELL00150 LNCaP; LAPC4; HEK293T; NK92; 22Rv1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell autophagy
unique00298 Since apoptosis resistance has been reported to be the underlying mechanism of therapy resistance in prostate cancer (PCa), Diallyl trisulfide could be used to effectively target PCa cells by overcoming apoptosis resistance and inducing ferroptosis-mediated cell death of PCa cells. Inducer . . . . . . REF000418 ICD-11: 2C82 Prostate cancer . . Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01212 The univariate, LASSO, and multivariate Cox regression analyses were performed to construct a prognostic signature. Seven FRGs,AKR1C3,ALOXE3, ATP5MC3,CARS1,MT1G,PTGS2, andTFRC, were included to establish a risk model, which was validated in the MSKCC dataset. Moreover, we found that TFRC overexpression induced the proliferation and invasion of prostate cancer (PCa) cell lines in vitro. . . . . Driver . . REF000470 ICD-11: 2C82 Prostate cancer CELL00057; CELL00283; CELL00051; CELL00108; CELL00150 HEK293T; C4-2; PC-3; LNCaP; 22RV1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration; Cell invasion
unique01607 ACO1 and IREB2 downregulation in kidney renal clear cell carcinoma were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. . . . . . Driver . REF000815 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00155 ACHN Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation; Cell metastasis; Cell invasion
unique01606 ACO1 and IREB2 downregulation in kidney renal clear cell carcinoma were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. . . . . Driver . . REF000815 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00155 ACHN Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation; Cell metastasis; Cell invasion
unique01645 MT1G affects ferroptosis by regulating GSH consumption in clear cell renal cell carcinoma (ccRCC) cells. MT1G may be a negative regulator of ferroptosis in ccRCC cells and a biomarker of poor prognosis. . . . . Suppressor . . REF000852 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00151; CELL00081 769-P; CAKI-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis; Cell proliferation
unique01099 SUV39H1 expression is frequently upregulated in clear cell renal cell carcinoma (ccRCC) tumors and is significantly correlated with ccRCC progression. Function loss of SUV39H1 in ccRCC tumors contributes the hypomethylation of the DPP4 promoter to upregulate DPP4 expression and induces DPP4-mediated ferroptosis to suppress cell proliferation. . . . . Suppressor . Female SCID mice (4-6 weeks old) were purchased and used for the xenograft models. Approximately 5 x 106 ccRCC cells were injected subcutaneously into the flank. The mice were treated with vehicle (control) or chaetocin (0.5 mg/kg/day) by daily intraperitoneal injection. REF000339 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00021; CELL00081; CELL00153; CELL00151; CELL00155; CELL00093 786-O; Caki-1; A498; 769-P; ACHN; HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell cycle
unique01782 ACADSB and MYCN are the favorable prognostic marker of clear cell renal cell carcinoma (ccRCC), while CDCA3, CHAC1, and TFAP2A are the unfavorable prognostic marker of ccRCC. . . . . Driver . . REF001011 ICD-11: 2C90 Clear cell renal cell carcinoma . . Ferroptosis (hsa04216) Cell ferroptosis
unique01250 Poor survival rates of clear cell renal cell carcinoma patients seem to be associated with up-regulation of the pentose phosphate pathway (PPP). KDM5C re-expression suppressed the glucose flux through PPP and re-sensitized cancer cells to ferroptosis. Furthermore, KDM5C deficiency predicted the poor prognosis, and clinically relevant KDM5C mutants failed to suppress glycogen accumulation and promoted ferroptosis as wild type. . . . . Driver . For the xenograft of RCC4 cells, four-week-old female NOD. At 6th week, mice were injected with 100 uL of stable RCC4-EV or RCC4-KDM5C cells suspended in Matrigel Basement Membrane Matrix (Corning, 356234) at a population of 1 x 107 cells into the left or right dorsal flank subcutaneously after alcohol sterilization of injection site skin surface. On day 7 after injection, the mice were randomly divided into 2 groups and treated with Liproxstatin-1 (10 mg/kg, MCE HY-12726) or vehicle control (1% DMSO in PBS) each other day by i.p. injection. REF000500 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00121; CELL00155; CELL00021; CELL00151; CELL00081; CELL00153; CELL00093 RCC4; ACHN; 786-O; 769-P; Caki-1; A498; HK-2 Pentose phosphate pathway (hsa00030); Ferroptosis (hsa04216) Cell ferroptosis
unique01100 SUV39H1 expression is frequently upregulated in clear cell renal cell carcinoma (ccRCC) tumors and is significantly correlated with ccRCC progression. Function loss of SUV39H1 in ccRCC tumors contributes the hypomethylation of the DPP4 promoter to upregulate DPP4 expression and induces DPP4-mediated ferroptosis to suppress cell proliferation. . . . . Driver . Female SCID mice (4-6 weeks old) were purchased and used for the xenograft models. Approximately 5 x 106 ccRCC cells were injected subcutaneously into the flank. The mice were treated with vehicle (control) or chaetocin (0.5 mg/kg/day) by daily intraperitoneal injection. REF000339 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00021; CELL00081; CELL00153; CELL00151; CELL00155; CELL00093 786-O; Caki-1; A498; 769-P; ACHN; HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell cycle
unique01132 The adipokine chemerin, which is encoded by the retinoic acid receptor responder 2 (RARRES2) gene, is overexpressed in clear cell renal cell carcinoma (ccRCC) due to both an autocrine, tumor-cell-dependent mechanism, as well as obesity-dependent paracrine production, and plays important roles in regulating lipid metabolism and tumorigenesis. . . . . Suppressor . Six-week-old female athymic nude mice (Charles River Laboratories) were used for xenograft studies. For subcutaneous tumor growth model, cells were pelleted and resuspended in a PBS/Matrigel Matrix (Corning, Cat# 356234) mix at 1:1 ratio. 2 x 106 cells in a 100 uL solution were injected subcutaneously into each flank. REF000365 ICD-11: 2C90 Clear cell renal cell carcinoma CELL00021; CELL00505; CELL00153; CELL00057; CELL00093 786-O; UOK101; A498; HEK293T; HK-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01864 Using lipidomic analysis, we found that AGPAT3-depletion selectively reduced the levels of the polyunsaturated species among both ether-linked and diacyl-phospholipids in renal cell carcinoma 786-O cells . Consistently, genetic AGPAT3-depletion suppressed sensitivity to ferroptosis. . . . . Driver . 3-4 week-old, male athymic nude mice were used for hosting the 786-O tumor xenografts. In the experiment that leads to isolation of ferroptosis-resistant 1 (FR1) cells , 5 x 106 wildtype or GPX4-/-single-cell clone (originally named as #3A7 clone3, then renamed as ferroptosis-sensitive (FS) GPX4-/-cells in the present study) of 786-O-Cas9 cells were resuspended in 50 ul sterile PBS containing 50 uM Fer-1, mixed with 50 ul Matrigel (BD Biosciences), and subcutaneously injected into both flanks of the mouse. REF000233 ICD-11: 2C90 Renal cell carcinoma CELL00021; CELL00151; CELL00453; CELL00012; CELL00057; CELL00211; CELL00042 786-O; 769-P; SNU-685; HuH-7; HEK-293T; OVCAR-8; SH-SY5Y Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01807 Using univariate and multivariate Cox regression, the study identified two independent prognostic genes, AMN and PDK4, and constructed an IRFG score model immune-related ferroptosis genes risk score (IRFGRs) to evaluate its prognostic value in clear cell renal cell carcinoma (ccRCC). . . . . Driver . . REF001037 ICD-11: 2C90 Clear cell renal cell carcinoma . . Ferroptosis (hsa04216) Cell ferroptosis
unique01316 RP11-89 "sponges" miR-129-5p and upregulates PROM2. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer. . . . . Suppressor . The male nude mice (BALB/c, aged 4-6 weeks, 18-20 g) were randomly divided into four groups (Sample size: 5-7 mice per group) and inoculated with cells as follows: sh-RP11-89 stable transfected 5637 Cell (1 x 107 cells); shNC-RP11-89 stable transfected 5637 Cell (1 x 107 cells); sh-RP11-89 stable transfected 5637 Cell + antagomiR-129-5p (1 x 107 cells; 10 nmol antagomiR-129-5p injection/mouse, 3 days after tumor formation); and sh-RP11-89 stable transfected 5637 Cell + miR-129-5p NC group (1 x 107 cells; 10 nmol miR-129-5p NC injection/mouse, 3 days after tumor formation). Cells were mixed with matrigel (1:2) and inoculated subcutaneously at the right rear back region. REF000570 ICD-11: 2C94 Bladder cancer CELL00067; CELL00136; CELL00438 5637; T24; BLCA; SV-HUC 1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique01318 RP11-89 "sponges" miR-129-5p and upregulates PROM2. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer. . . . . Driver . The male nude mice (BALB/c, aged 4-6 weeks, 18-20 g) were randomly divided into four groups (Sample size: 5-7 mice per group) and inoculated with cells as follows: sh-RP11-89 stable transfected 5637 Cell (1 x 107 cells); shNC-RP11-89 stable transfected 5637 Cell (1 x 107 cells); sh-RP11-89 stable transfected 5637 Cell + antagomiR-129-5p (1 x 107 cells; 10 nmol antagomiR-129-5p injection/mouse, 3 days after tumor formation); and sh-RP11-89 stable transfected 5637 Cell + miR-129-5p NC group (1 x 107 cells; 10 nmol miR-129-5p NC injection/mouse, 3 days after tumor formation). Cells were mixed with matrigel (1:2) and inoculated subcutaneously at the right rear back region. REF000570 ICD-11: 2C94 Bladder cancer CELL00067; CELL00136; CELL00438 5637; T24; BLCA; SV-HUC 1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique01317 RP11-89 "sponges" miR-129-5p and upregulates PROM2. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer. . . . . Suppressor . The male nude mice (BALB/c, aged 4-6 weeks, 18-20 g) were randomly divided into four groups (Sample size: 5-7 mice per group) and inoculated with cells as follows: sh-RP11-89 stable transfected 5637 Cell (1 x 107 cells); shNC-RP11-89 stable transfected 5637 Cell (1 x 107 cells); sh-RP11-89 stable transfected 5637 Cell + antagomiR-129-5p (1 x 107 cells; 10 nmol antagomiR-129-5p injection/mouse, 3 days after tumor formation); and sh-RP11-89 stable transfected 5637 Cell + miR-129-5p NC group (1 x 107 cells; 10 nmol miR-129-5p NC injection/mouse, 3 days after tumor formation). Cells were mixed with matrigel (1:2) and inoculated subcutaneously at the right rear back region. REF000570 ICD-11: 2C94 Bladder cancer CELL00067; CELL00136; CELL00438 5637; T24; BLCA; SV-HUC 1 Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell invasion
unique01848 The study report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury and neuroblastoma in mice. Suppressor . . . . . All mice treated with iron sulfate received an intraperitoneal injection of 300 mg/kg body weight FeSO4·7H2O dissolved in sterile 0.9% NaCl or vehicle (0.9% NaCl). The injection volume was 200 uL/20 g body weight. Vehicle solution (2% DMSO) or compound was administered at a concentration of 2 mM (in 0.9% NaCl containing 2% DMSO; 200 uL/20 g body weight) by intravenous injection 15 min before IP injection with FeSO4·7H2O. Two hours after iron sulfate injection, mice were anesthetized with isoflurane and blood was sampled. REF000053 ICD-11: 2D50 Neuroblastoma CELL00100 IMR-32 Ferroptosis (hsa04216) Cell ferroptosis
unique01847 The study report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury and neuroblastoma in mice. Suppressor . . . . . All mice treated with iron sulfate received an intraperitoneal injection of 300 mg/kg body weight FeSO4·7H2O dissolved in sterile 0.9% NaCl or vehicle (0.9% NaCl). The injection volume was 200 uL/20 g body weight. Vehicle solution (2% DMSO) or compound was administered at a concentration of 2 mM (in 0.9% NaCl containing 2% DMSO; 200 uL/20 g body weight) by intravenous injection 15 min before IP injection with FeSO4·7H2O. Two hours after iron sulfate injection, mice were anesthetized with isoflurane and blood was sampled. REF000053 ICD-11: 2D50 Neuroblastoma CELL00100 IMR-32 Ferroptosis (hsa04216) Cell ferroptosis
unique01846 The study report the synthesis of a more stable and readily soluble series of Fer-1 analogues that potently inhibit ferroptosis. The most promising compounds (37, 38, and 39) showed an improved protection compared to Fer-1 against multiorgan injury and neuroblastoma in mice. Suppressor . . . . . All mice treated with iron sulfate received an intraperitoneal injection of 300 mg/kg body weight FeSO4·7H2O dissolved in sterile 0.9% NaCl or vehicle (0.9% NaCl). The injection volume was 200 uL/20 g body weight. Vehicle solution (2% DMSO) or compound was administered at a concentration of 2 mM (in 0.9% NaCl containing 2% DMSO; 200 uL/20 g body weight) by intravenous injection 15 min before IP injection with FeSO4·7H2O. Two hours after iron sulfate injection, mice were anesthetized with isoflurane and blood was sampled. REF000053 ICD-11: 2D50 Neuroblastoma CELL00100 IMR-32 Ferroptosis (hsa04216) Cell ferroptosis
unique00862 CISD2 inhibition overcomes head and neck cancer (HNC) resistance to ferroptotic cell death induced by sulfasalazine via increased accumulation of mitochondrial ferrous iron and lipid ROS. . . . . . Driver/Suppressor Six-week-old athymic BALB/c malenude mice(nu/nu) were purchased from the Central Lab Animal Inc. (Seoul, Republic of Korea). SAS-resistant HN10 cells were injected subcutaneously into the flank of nude mice. Following the detection of gross nodules from the tumor implants, the mice were subjected to four different treatments: vehicle, SAS (250mg/kg daily per intraperitoneal route), PGZ (20 mg/kg daily per oral administration), or SAS plus PGZ. REF000043 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00467; CELL00521; CELL00451; CELL00452 AMC-HN211; SNU-1041; SNU-1066; SNU-1076 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00952 Dihydrolipoamide dehydrogenase (DLD) regulates cystine deprivation-induced ferroptosis in head and neck cancer. DLD inhibition decreases both lipid peroxidation and ferrous iron accumulation, resulting in ferroptosis suppression. . . . . Driver . Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN9 cells with shDLD or vector control were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). REF000124 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00491; CELL00519; CELL00494 HN3; HN4; HN9 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Citrate cycle (hsa00020) Cell ferroptosis
unique00006 Artesunate induced ferroptosis in head and neck cancer (HNC) cells by decreasing cellular GSH levels and increasing lipid ROS levels. This effect was blocked by co-incubation with ferrostatin-1 and a trolox pretreatment. Artesunate activated the Nrf2-antioxidant response element (ARE) pathway in HNC cells, which contributed to ferroptosis resistance. Suppressor . . . . . . REF000017 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00522; CELL00006 HN210; SNU Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01130 The regulation of a KDM5A-MPC1 axis contributes to promoting ferroptosis susceptibility in head and neck cancer (HNC) cells, which might be recommended as a promising combination therapy in combating drug-tolerant persister cancer cells. . . . . Driver . Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN4 parental cells with transfection of vector control or shGPX4 were subcutaneously injected into the bilateral flank of nude mice. The same was performed in HN4 erPCC with transfection of control vector or shGPX4. Each group included six mice. In other experiments, HN4 parental cells with transfection of control vector or shMPC1 were injected to nude mice in the same way above. HN4 parental cells and erPCC without target gene silencing were also injected into nude mice. Each group included six mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). REF000363 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00491; CELL00519 HN3; HN4 Glutamate metabolism (hsa00250); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01129 The regulation of a KDM5A- MPC1 axis contributes to promoting ferroptosis susceptibility in head and neck cancer (HNC) cells, which might be recommended as a promising combination therapy in combating drug-tolerant persister cancer cells. . . . . Suppressor . Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN4 parental cells with transfection of vector control or shGPX4 were subcutaneously injected into the bilateral flank of nude mice. The same was performed in HN4 erPCC with transfection of control vector or shGPX4. Each group included six mice. In other experiments, HN4 parental cells with transfection of control vector or shMPC1 were injected to nude mice in the same way above. HN4 parental cells and erPCC without target gene silencing were also injected into nude mice. Each group included six mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). REF000363 ICD-11: 2D60 Head and neck squamous cell carcinoma CELL00491; CELL00519 HN3; HN4 Glutamate metabolism (hsa00250); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01772 Thyroid associated ophthalmopathy (TAO) is an orbital autoimmune inflammatory disease that is commonly associated with thyroid dysfunction. In vitro,experiments revealed that CTSB, PEX3, ABCC1 and ZFHX4-AS1 (lncRNA) were differentially expressed in orbital fibroblasts (OFs) between TAO groups and healthy controls at the transcriptional level. . . . . Driver . . REF001002 ICD-11: 5A02 Thyroid associated ophthalmopathy . . Ferroptosis (hsa04216) Cell ferroptosis
unique01029 FXN, amitochondrial proteininvolved iniron metabolismandROSregulation, was shown by other studies reduced in diabetic islets than nondiabetic and impaired insulin secretion after disruption in mice pancreatic -cells. . . . . Suppressor . . REF000244 ICD-11: 5A10 Diabetes mellitus CELL00602 INS-1 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01808 Diabetic peripheral neuropathy (DPN) is a serious complication in Diabetes Mellitus (DM) patients. Key modules constructed by the protein-protein interaction network analysis led to the confirmation of the following genes of interest: DCAF7, GABARAPL1, ACSL4, SESN2 and RB1. . . . . Driver . . REF001039 ICD-11: 5A10 Diabetes mellitus . . Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01131 The BEX1 gene is differentially expressed in aldosterone-producing adenomas (APAs) according to nodule diameter and protects human adrenocortical cells in vitro from a form of regulated cell death called ferroptosis. . . . . Suppressor . . REF000364 ICD-11: 5A72 Aldosteron producing adenoma CELL00529 HAC15 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01753 The study identified five ferroptosis-related genes (NOX1, ACVR1B, PHF21A, FTL, and GALNT14) that may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), which may provide a novel perspective for the clinical diagnosis and treatment of PCOS. . . . . Driver . . REF000973 ICD-11: 5A80.1 Polycystic ovary syndrome CELL10091 Ovarian granulosa cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00360 Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types. Chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastatic capacity. Notably, the metabolic stress imposed upon cells by the accumulated lipids requires sustained expression of GPX4, a negative regulator of ferroptotic cell death. Suppressor . . . . . C57BL/6 and Balb/C mice were purchased from Jackson Laboratories. During tumor studies, mice were monitored daily, and tumors volume was measured as an index of the growth rate and calculated as (width+length)/2 x width x length x 0.5236. Experimental metastasis was studied by injecting viable 27HCS-, and 27HCR of 4T1 (200,000), Py230 (300,000-500,000), BPD6 (200,000) cells, with or without luciferase labeling (suspended in ice-cold 200 ul HBSS) into the lateral tail veins of athymic or syngeneic mice. REF000488 ICD-11: 5C80 Hypercholesterolemia CELL00540; CELL00523; CELL00582; CELL00349; CELL10135; CELL00007; CELL00484; CELL00170; CELL00002; CELL00581; CELL00563 4T1; Met1; E0771; MDAMB436; BPD6; B16F10; 293FT; HCC1954; MCF7; Py230; Py8119 Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis; Cell proliferation; Cell migration
unique00963 ACHYL1 is a interaction protein of DJ-1, which also has been known for negatively regulating SAHH (AHCY) activity via forming a heteromultimer complex. DJ-1 mutant neuronal cells experience high levels of ferroptosis, which might establish a potential mechanism via which DJ-1 could regulate early-onset recessive Parkinsons disease. . . . . Suppressor . Tumors were established by a subcutaneous injection of shRNA (control or DJ-1 KD) transfected H1299 cells (1,000,000/200 uL) into BALB/c female athymic nude mice (5 weeks, National Rodent Laboratory Animal Resource, Shanghai, China). Twelve days after injection, mice were randomly allocated into different groups and treated with vehicle (0.625% DMSO/99.375% HBSS (pH = 2)) or 30 mg/kg PE (tail intravenous injection, once every other day) for 16 days before the final tumor size was measured in all groups. REF000144 ICD-11: 8A00 Parkinson disease CELL00056; CELL00045; CELL00120; CELL00117; CELL00384; CELL00021; CELL00412; CELL00070; CELL00057 H1299; A549; PANC1; H292; H838; 786-O; KHOS; A2780; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00977 Variations in the SNCA gene that lead to increased -synuclein expression represent a genetic risk factor for sporadic parkinsons disease. a-synuclein aggregates may induce ferroptosis, and that inhibitors of ferroptosis prevent -synuclein-induced cell death. . . . . Driver . . REF000168 ICD-11: 8A00 Parkinson disease CELL10077; CELL10060 Human induced pluripotent stem cell (iPSC); Human embryonic stem (ES) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00486 1,6-O,O-diacetylbritannilactone (OABL) also significantly reduced the accumulation of amyloid plaques, the A expression, the phosphorylation of Tau protein, and the expression of BACE1 in Alzheimer's disease mice brain. OABL attenuated the overactivation of microglia and astrocytes by suppressing the expressions of inflammatory cytokines, and increased glutathione (GSH) and reduced malondialdehyde (MDA) and super oxide dismutase (SOD) levels in the 5xFAD mice brain. Suppressor . . . . . OABL (20 mg/kg per day) dissolved in water with 10% ethanol and 10% Tween 80 was administrated to 6-month-old WT and 5xFAD mice for 3 weeks. WT+OABL and 5xFAD+OABL groups were treated by an intraperitoneal (i.p.) injection of OABL as the above-mentioned. OABL were dissolved in 10% ethanol, 10% Tween 80 and distilled water (according to 0.1% w/vol), and this solution of 10% ethanol, 10% Tween 80, and 80% distilled water was used as the vehicle. Mice from WT+Vehicle group and 5xFAD+Vehicle group were injected with the vehicle. Additional animal tests were conducted afteri.p.injection. REF000645 ICD-11: 8A20 Alzheimer's disease CELL00544; CELL00597 BV-2; PC12 Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00113 Apigenin can efficiently reduce the expression of intracellular MPO and increase the levels of GPX4 and SIRT1, thereby conferring neuroprotection through regulation of kainic acid (KA)-induced ferroptosis. And the level of Ac-p53 inside the brains treated with apigenin was down-regulated, suggesting that the p53-mediated ferroptosis pathway might be blocked. Overall, apigenin was screened and confirmed as an efficient lead compound for epilepsy prevention and treatment. Inducer . . . . . 5-weeks-old kainate (KA)-induced BALB/c nude mice, a widely used epilepsy mouse model, were performed with intraperitoneal (i.p.) injection of KA (6 mg/kg). Pre-treatment 21 with antioxidant apigenin (60 mg/Kg, 2 days) or post-treatment with apigenin (60 mg/Kg, 1 day), mice were injected with KA (6 mg/kg) via intraperitoneal (i.p.) injection, and then HCP (0.5 mg/Kg) were injected by intravenous (i.v.) injection. In vivo and Ex vivo fluorescence images of relative ClO levels in mice brains 5, 15, 30, 45, and 60 min post injection of HCP were further performed by using the IVIS Spectrum imaging system (Nanjing University) with an excitation filter of 430 nm and the collection wavelength range is from 500-600 nm. REF000165 ICD-11: 8A66 Epilepsy CELL00042 SH-SY5Y Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00474 Ferroptosis is an iron-dependent mechanism of regulated necrosis that has been linked to hemorrhagic stroke. The mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor U0126 inhibits persistent ERK1/2 phosphorylation and ferroptosis. Suppressor . . . . . Male C57BL/6 mice (8-10 weeks old) were purchased from Charles River Laboratories. For intraperitoneal injections, mice received daily intraperitoneal injections of 25 mg/kg U0126 or vehicle for 7 d (n = 13 for sham+vehicle, n = 17 for ICH+vehicle, n = 16 for ICH + 25 mg/kg U0126). Four ICH and six ICH+U0126 animals died from the surgery. For intracerebroventricular injections, mice received a single intracerebroventricular injection of 12 ug U0126 or vehicle (n = 16 per group) 2 h after ICH. REF000634 ICD-11: 8B00 Hemorrhagic stroke CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01657 The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in ischemia-reperfusion (I/R) model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression. . . . . Suppressor . Wild-type SD rats were kept in the Animal Experiment Center of Southeast University. Experimental rats were divided into 4 groups (n = 6 per group). The method of establishing the I/R model was provided in supplementary material. Then, we covered the ligation with gel. In order to fully cover the infarcted area of the heart, we chose to inject about 300 uL of mimics + Gel at 23 mm below the left atrial appendage (about the ligation). In order to prevent excessive irradiation of tissue burns, we selected each irradiation for 2 min to control the body surface temperature for a total of 10 min of irradiation. REF000866 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00030 H9c2 Fatty acid metabolism (hsa01212) Cell ferroptosis
dupunique01657 The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in ischemia-reperfusion (I/R) model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression. . . . . Driver . Wild-type SD rats were kept in the Animal Experiment Center of Southeast University. Experimental rats were divided into 4 groups (n = 6 per group). The method of establishing the I/R model was provided in supplementary material. Then, we covered the ligation with gel. In order to fully cover the infarcted area of the heart, we chose to inject about 300 uL of mimics + Gel at 23 mm below the left atrial appendage (about the ligation). In order to prevent excessive irradiation of tissue burns, we selected each irradiation for 2 min to control the body surface temperature for a total of 10 min of irradiation. REF000866 ICD-11: 8B10-8B11 Cerebral ischemia-reperfusion injury CELL00030 H9c2 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01268 OGD combined with hyperglycemic reperfusion promoted Meg3 expression and there was positive correlation between Meg3 and p53 expression in RBMVECs. Subsequently, p53 inhibited the activity of GPX4 by binding with its promoter. The Meg3-p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion and Meg3 has been considered as an important mediator in regulating diabetic brain ischemic injury. . . . . Driver . Sprague Dawley (SD) rats (n = 60) aged three weeks were purchased from the Experimental Animal Center of Xiangya Hospital of Central South University. All rats were bred in a specific pathogen-free environment in 12-h lightdark cycle and fed with rodent diet and water. All rats were anaesthetized with inhaling isoflurane (2%, CAS NO. 64181101, Lunan Pharmaceutical Co., LTD. Shandong, China) and sacrificed by cervical dislocation. The whole brain was removed after opening the cranial cavity. REF000517 ICD-11: 8B11 Diabetic brain ischemic injury CELL10046 RBMVECs Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
dupunique01268 OGD combined with hyperglycemic reperfusion promoted Meg3 expression and there was positive correlation between Meg3 and p53 expression in RBMVECs. Subsequently, p53 inhibited the activity of GPX4 by binding with its promoter. The Meg3- p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion and Meg3 has been considered as an important mediator in regulating diabetic brain ischemic injury. . . . . Driver . Sprague Dawley (SD) rats (n = 60) aged three weeks were purchased from the Experimental Animal Center of Xiangya Hospital of Central South University. All rats were bred in a specific pathogen-free environment in 12-h lightdark cycle and fed with rodent diet and water. All rats were anaesthetized with inhaling isoflurane (2%, CAS NO. 64181101, Lunan Pharmaceutical Co., LTD. Shandong, China) and sacrificed by cervical dislocation. The whole brain was removed after opening the cranial cavity. REF000517 ICD-11: 8B11 Diabetic brain ischemic injury CELL10046 RBMVECs Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
dupunique01013 PVT1 regulates ferroptosis through miR-214-mediated p53 and TFR1. The discovery of PVT1 and miR-214 as potential targets for I/R also implies that PVT1 and miR-214 play critical roles in ferroptosis, shedding new light on the mechanism of ferroptosis in acute ischemic stroke. . . . . Driver . . REF000219 ICD-11: 8B11 Acute ischemic stroke CELL00597 PC12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00367 Compound Tongluo Decoction could improve the signs of cerebral infarction and inhibit ferroptosis induced by ER stress as well as promote angiogenesis by activating SHH pathway in rats and cells with cerebral infarction. Suppressor . . . . . Thirty male Sprague-Dawley (SD) rats (body weight 250 g-280 g) were purchased from Nanjing University of Chinese Medicine. Rats were anesthetized with 1% pentobarbital sodium and fixed in a supine position. Both the proximal ends of common carotid artery and external carotid artery were ligated, and the internal carotid artery was clamped temporarily. A V-shaped oblique incision was made at the bifurcation of external carotid and internal carotid arteries with vascular scissors. Then, reopening the artery clamp and inserting a paraffin bolt into internal carotid artery through the external carotid artery stump until a slight resistance was felt. The time was considered as the beginning of embolism and the upper end of the common carotid artery was then ligated. Finally, 90 min after embolization, the paraffin bolt was gently pulled back to the incision of external carotid artery for reperfusion. REF000504 ICD-11: 8B1Z Cerebral infarction CELL00597 PC12 Hedgehog signaling pathway (hsa04340); Ferroptosis (hsa04216); Lipid and atherosclerosis (hsa05417) Cell ferroptosis
unique01294 Cofilin1 (CFL1) acts as a redox sensor in oxidative cell death pathways of ferroptosis, and also promotes glutamate excitotoxicity. Protective effects by cofilin1 inhibition are particularly attributed to preserved mitochondrial integrity and function. Thus, interfering with the oxidation and pathological activation of cofilin1 may offer an effective therapeutic strategy in neurodegenerative diseases. . . . . Driver . . REF000545 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Gluconeogenesis (hsa00010) Cell ferroptosis; Cell proliferation
unique00481 Cannabinol directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis. Oxytosis/ferroptosis recapitulates several aspects of mitochondrial pathology that are relevant to neurodegenerative diseases. Suppressor . . . . . . REF000637 ICD-11: 8E7Z Neurodegenerative disease CELL00549; CELL00042; CELL00544 HT22; SH-SY5Y; BV2 Ferroptosis (hsa04216); Calcium signaling pathway (hsa04020) Cell ferroptosis; Cell proliferation
unique00357 GIF-2114 and GIF-2197-r (the racemate of GIF-2115 and GIF-2196), did not affect glutathione levels, had no antioxidant activity in vitro, or ability to activate the Nrf2 pathway, but prevented oxytosis/ferroptosis via reducing reactive oxygen production and decreasing ferrous ions related to neurodegenerative disorders. Suppressor . . . . . . REF000484 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00356 GIF-2114 and GIF-2197-r (the racemate of GIF-2115 and GIF-2196), did not affect glutathione levels, had no antioxidant activity in vitro, or ability to activate the Nrf2 pathway, but prevented oxytosis/ferroptosis via reducing reactive oxygen production and decreasing ferrous ions related to neurodegenerative disorders. Suppressor . . . . . . REF000484 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00819 Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases. The PI3K (PIK3CA) inhibitor protects cells by inducing partial restoration of depleted glutathione levels and accumulation of intracellular amino acids, whereas the Flt3 inhibitor prevents lipid peroxidation, a key mechanism of glutamate-mediated toxicity. . . . . Driver . Whole cerebral neocortices were removed from the rat fetuses, and incubated in 0.03% trypsin in Earles balanced salt solution (EBSS) without Ca2 + or Mg2 + for 90 min at 37. Subsequently, the cortices washed with fresh EBSS, transferred into culture medium (12.5% F-12 growth media (Sigma), 12.5% heat inactivated horse serum (Hyclone), 30 U/ml Penicillin, 0.03 mg/ml Streptomycin solution (both Sigma), 2.5 mM glutamine (Sigma), 10 mM HEPES (Omega) in DMEM with high glucose (4500 g/l, Sigma) and dissociated by trituration. REF000002 ICD-11: 8E7Z Neurodegenerative diseases CELL00549; CELL00576; CELL00574; CELL00593 HT22; 661W; RGC-5; C6 Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217); Citrate cycle (hsa00020) Cell ferroptosis; Cell apoptosis; Cell necrosis
unique00820 Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases. The PI3K (PIK3CA) inhibitor protects cells by inducing partial restoration of depleted glutathione levels and accumulation of intracellular amino acids, whereas the Flt3 inhibitor prevents lipid peroxidation, a key mechanism of glutamate-mediated toxicity. . . . . Driver . Whole cerebral neocortices were removed from the rat fetuses, and incubated in 0.03% trypsin in Earles balanced salt solution (EBSS) without Ca2 + or Mg2 + for 90 min at 37. Subsequently, the cortices washed with fresh EBSS, transferred into culture medium (12.5% F-12 growth media (Sigma), 12.5% heat inactivated horse serum (Hyclone), 30 U/ml Penicillin, 0.03 mg/ml Streptomycin solution (both Sigma), 2.5 mM glutamine (Sigma), 10 mM HEPES (Omega) in DMEM with high glucose (4500 g/l, Sigma) and dissociated by trituration. REF000002 ICD-11: 8E7Z Neurodegenerative diseases CELL00549; CELL00576; CELL00574; CELL00593 HT22; 661W; RGC-5; C6 Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217); Citrate cycle (hsa00020) Cell ferroptosis; Cell apoptosis; Cell necrosis
unique00106 Iron is essential for normal neuronal function, and excess iron in the brain is implicated in several neurodegenerative diseases. Chelating neurotoxic iron with deferiprone ameliorated general anaesthesia (GA)-induced cognitive deficits and suggest that iron restriction might provide a preventative effect for paediatric patients undertaking GA. Suppressor . . . . . Sprague-Dawley rat pups at postnatal day (PND) 6 and 15-month-old male C57BL/6 mice were used in the present study. For ketamine GA, rat pups at PND 6 or 15-month-old mice received ketamine (75 mg/kg) intraperitoneally daily for three consecutive days. For sevoflurane GA, animals were put in an anaesthetizing chamber delivered with 3% sevoflurane plus 30% oxygen (O2) for 2 h daily for three consecutive days. For control experiments, 30% O2 was delivered at the same flow rate. For drug treatment, DFP (75 mg/kg, intraperitoneally, synthesized in China Peptides Co., Ltd., Shanghai, China) or DMT1i (50 mg/kg, orally, MedChemExpress, China) was administered to the animals 1 h before GA daily for three consecutive days. REF000159 ICD-11: 8E7Z Neurodegenerative diseases CELL10170 Hippocampal neuronal Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00039 The ethanol extracts of Brazilian green propolis help to prevent oxidative stress-related neuronal cell death that is involved in the pathogenesis of several neurodegenerative diseases. Among the primary constituents of ethanol extracts of Brazilian green propolis, only artepillin C, kaempferide, and kaempferol demonstrated neuroprotective effects against oxytosis/ferroptosis. Suppressor . . . . . . REF000075 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique00040 The ethanol extracts of Brazilian green propolis help to prevent oxidative stress-related neuronal cell death that is involved in the pathogenesis of several neurodegenerative diseases. Among the primary constituents of ethanol extracts of Brazilian green propolis, only artepillin C, kaempferide, and kaempferol demonstrated neuroprotective effects against oxytosis/ferroptosis. Suppressor . . . . . . REF000075 ICD-11: 8E7Z Neurodegenerative diseases CELL00549 HT22 Ferroptosis (hsa04216) Cell ferroptosis
unique01611 Excessive oxidative stress-induced ferroptosis participates in dry eye disease (DED) pathogenesis. The expression of AKR1C1 is triggered by NRF2 to decrease ferroptosis-induced cell damage and inflammation in HCECs. . . . . Suppressor . A total of 72 female C57BL/6J mice aged 6 to 8 weeks were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). The mice were injected subcutaneously with scopolamine hydrobromide (1.5 mg/0.3 mL; Sigma-Aldrich) three times daily for 5 consecutive days. Control mice matched for age and sex were maintained in an environment of 50% to 75% relative humidity. REF000821 ICD-11: 9A79 Dry eye disease CELL00432 HCE-2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01610 Diabetic retinopathy (DR) as a severe diabetic complication contributes to blindness. TRIM46 interacts with IB to activate the NF-B signaling pathway, thereby enhancing cell proliferation inhibition, hyper permeability and the inflammatory response of HRCECs in a HG state. . . . . Driver . . REF000820 ICD-11: 9B71.0 Diabetic retinopathy CELL10098 HRCECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell proliferation
unique00258 Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. SI depletes GSH, increases ROS, releases labile iron, and boosts lipid damage, which in turn results in ferroptosis in ARPE-19 cells. Inducer . . . . . . REF000346 ICD-11: 9B78 Peripheral retinal degeneration CELL00072; CELL00096; CELL00042; CELL00059 ARPE-19; HT-29; SH-SY5Y; Jurkat; Mouse primary RPE cells Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique00513 The active ingredients of Eucommia ulmoides Oliver-Tribulus terrestrisL (EUO-TT) drug pair may act on proteins associated with the neuroactive ligand-receptor interaction pathway to regulate ferroptosis in vascular neurons cells, ultimately affecting the onset and progression of hypertension. Suppressor . . . . . . REF000700 ICD-11: BA00 Hypertension . . Ferroptosis (hsa04216) Cell ferroptosis
unique01263 AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of acute myocardial infarction (AMI). . . . . Suppressor . . REF000512 ICD-11: BA41 Acute myocardial infarction CELL00057; CELL00030 293T; H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01310 CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction. . . . . Suppressor . C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min. REF000565 ICD-11: BA41 Myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01264 AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of acute myocardial infarction (AMI). . . . . Suppressor . . REF000512 ICD-11: BA41 Acute myocardial infarction CELL00057; CELL00030 293T; H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01311 CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction. . . . . Driver . C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min. REF000565 ICD-11: BA41 Myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01312 CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction. . . . . Suppressor . C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min. REF000565 ICD-11: BA41 Myocardial infarction CELL00548 HL-1 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00736 ROS-induced autophagy contributed to the consequent development of ferroptosisin vitro and in vivo. Idebenone alleviated ferroptosis by regulating excessive autophagy via the AMPK-mTOR pathway in myocardial infarction. Suppressor . . . . . The mice were randomly divided into 3 groups as follows: sham + vehicle (5% DMSO + 10% PEG + 20% Tween80) group; MI + vehicle group; and MI + idebenone group. The 3 groups of mice then received vehicle or idebenone (100 mg/kg) in a final volume of 100 uL by intraperitoneal injections (Lee et al., 2021) 24 h and 2 h prior to surgery. A mouse model of MI was used as previously described (Guo et al., 2022b). In short, mice were placed under general anesthesia by intraperitoneal injection of pentobarbital, then endotracheal intubation and artificial respiration were performed. The left anterior descending coronary artery (LAD) of mice was ligated with a 6-0 silk suture, and the color of the LAD wall becoming pale confirmed the occlusion of the vessel. The same procedures were carried out on mice in the sham operation group, but with no LAD occlusion. The 3 groups of mice then received vehicle or idebenone (100 mg/kg/day) in a final volume of 100 uL by intraperitoneal injections once daily for 3 days. REF000959 ICD-11: BA41 Myocardial infarction CELL00030 H9C2 Ferroptosis (hsa04216); mTOR signaling pathway (hsa04150) Cell ferroptosis; Cell autophagy
unique00663 SGLT2 inhibitor empagliflozin may be considered in TZM-elicited cardiotoxicity (including cardiac remodeling and contractile dysfunction, DNA damage, oxidative stress and cell death). Suppressor . . . . . All animal procedures were approved by the Animal Care and Use Committees at the Second Affiliated Hospital of Nanchang University (Nanchang, China) and Zhongshan Hospital Fudan University (Shanghai, China). In brief, adult male C57BL/6J mice were intraperitoneally delivered TZM at a dose of 10 mg/kg once per week for 6 weeks. A cohort of mice received Empagliflozin at a dose of 10 mg/kg twice per week for 6 weeks. All mice were maintained on a 12/12-light/dark cycle with free access to tap water and lab chow until experimentation. Blood glucose and serum triglyceride levels were obtained using a commercial glucometer and ELISA commercial kits, respectively. Serum levels oflactic dehydrogenase(LDH) and troponin I were measured using chemiluminescent immunoassays. To discern the involvement of ferroptosis in TZM-induced cardiotoxicity, a cohort of TZM challenged C57BL/6J mice (10 mg/kg once per week for 4 weeks) also received the ferroptosis inhibitor liproxtatin-1 (LIP-1, 10 mg/kg, i.p., every other day) during the entire duration of TZM challenge. REF000891 ICD-11: BC43 Cardiomyopathy CELL00586 mouse cardiomyocytes Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01003 MLK3 (MAP3K11) mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. . . . . Driver . Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively. REF000203 ICD-11: BD1Z Chronic heart failure CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Necroptosis (hsa04217); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell pyroptosis
dupunique01004 MLK3 (MAP3K11) mainly regulates the JNK/ p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. . . . . Driver . Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively. REF000203 ICD-11: BD1Z Chronic heart failure CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Necroptosis (hsa04217); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell pyroptosis
unique01004 MLK3 (MAP3K11) mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. . . . . Suppressor . Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively. REF000203 ICD-11: BD1Z Chronic heart failure CELL10171 Heart tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Necroptosis (hsa04217); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis; Cell pyroptosis
unique00426 Pulmonary microvascular barrier dysfunction plays an important role in chronic obstructive pulmonary disease complicated with atherosclerosis, and ferroptosis may be involved. Moreover, Tongxinluo (TXL) delays the progression of AS and reduces cardiovascular events by protecting the pulmonary microvascular barrier and inhibiting ferroptosis. Suppressor . . . . . The mice were randomly divided into the following six groups (n = 10 per group): the control (CON) group, which included C57BL/6 mice that were exposed to ambient air only, fed standard rodent chow (Beijing Keao Xieli Feed Co., Ltd., Beijing, China) and perfused with 0.5% carboxymethylcellulose (CMC) sodium solution; the high-fat diet (HFD) group, which included ApoEmice that were exposed to ambient air, fed a high-fat and high-cholesterol diet and perfused with 0.5% CMC sodium solution; the CS and HFD (CS+HFD) group, which included ApoEmice that were exposed to CS in a glass box, fed a HFD, and perfused with 0.5% CMC sodium solution; theATOgroup, which included ApoEmice (exposed to CS and HFD) that were perfused with 0.01 g/kg/day ATO calcium tablets; the TXL group, which included ApoEmice (exposed to CS and HFD) that were perfused with 0.75 g/kg/day TXL ultrafine powder; and the ATO/TXL combination therapy (ATO+TXL) group, which included ApoEmice (exposed to CS and HFD) that were perfused with a combination of 0.01 g/kg/day ATO and 0.75 g/kg/day TXL. REF000572 ICD-11: CA22 Chronic obstructive pulmonary disease complicated with atherosclerosis CELL10033 HPMEC Glutathione metabolism (hsa00480); Ferroptosis (hsa04216) Cell ferroptosis
unique01237 Asthma occurs accompanied by the ferroptosis in bronchial epithelial cells, during which Interleukin-6 (IL-6) plays a key role. IL-6 promotes ferroptosis in bronchial epithelial cells by inducing reactive oxygen species (ROS)-dependent lipid peroxidation and disrupting iron homeostasis. . . . . Driver . . REF000483 ICD-11: CA23 Asthma CELL00076 BEAS-2B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00839 Cystic fibrosis transmembrane conductance regulator (CFTR) is the essential chloride and bicarbonate channel in the apical membrane of epithelial cells. ANO6 and CFTR act cooperatively on ROS-mediated cell death, which is not further augmented by cAMP-dependent stimulation. . . . . Driver . . REF000023 ICD-11: CA25 Cystic fibrosis CELL00004; CELL00049; CELL00517 HEK293; HeLa; CFBE Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01328 The epithelial-mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. SETDB1 regulates the expression of Snai1 by catalyzing the histone H3 lysine 9 trimethylation (H3K9me3) of Snai1, the main transcription factor that initiates the process of EMT, and thus, indirectly regulates E-cadherin (CDH1). And overexpressed SETDB1 alleviated EMT and also caused ferroptosis. . . . . Driver . Forty Sprague-Dawley rats (weight 200 ± 20 g) were obtained from the Experimental Animal Center of Henan Province. The pulmonary fibrosis rat model was established using previously described techniques. The rats were administered a tracheal infusion of bleomycin at a concentration of 5 mg/kg in sterile 0.9% NaCl. REF000588 ICD-11: CB03 Chronic obstructive pulmonary disease complicated with atherosclerosis CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis
unique01327 The epithelial-mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. SETDB1 regulates the expression of Snai1 by catalyzing the histone H3 lysine 9 trimethylation (H3K9me3) of Snai1, the main transcription factor that initiates the process of EMT, and thus, indirectly regulates E-cadherin (CDH1). And overexpressed SETDB1 alleviated EMT and also caused ferroptosis. . . . . Suppressor . Forty Sprague-Dawley rats (weight 200 ± 20 g) were obtained from the Experimental Animal Center of Henan Province. The pulmonary fibrosis rat model was established using previously described techniques. The rats were administered a tracheal infusion of bleomycin at a concentration of 5 mg/kg in sterile 0.9% NaCl. REF000588 ICD-11: CB03 Chronic obstructive pulmonary disease complicated with atherosclerosis CELL00045 A549 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Cell adhesion molecules (hsa04514) Cell ferroptosis
unique01865 Quercetin induced EB-mediated lysosome activation and increased ferritin degradation leading to ferroptosis and Bid-involved apoptosis in hepatoblastoma cells. . . . . Driver . . REF000288 ICD-11: DB91 Hepatoblastoma CELL00048; CELL00098; CELL00005; CELL00087 HepG2; Hep3B; MDA-MB-231; HCT116 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01332 Berberine induced iron disruption in HSCs by modulating ferritin degradation in both the autophagy/ROS and UPS pathways, driving HSC ferroptosis to attenuate liver fibrosis. Inducer . . . . . 6-week-old male mice (20-25 g) were randomly allocated to the indicated groups and housed in cages with ad libitum access to food and water, following habituation to a 12 h light/dark cycle. The experimenter was blinded to the group allocation. The mouse liver fibrosis model group was established via intraperitoneal (i.p.) injection with TAA or carbon tetrachloride (CCl4) for 6 weeks. The control group was injected i.p. with the same volume of olive oil or saline only. For the BBR group, a dose of BBR (200 mg/kg/day) was given by oral gavage. In addition to the i.p. injection. with TAA or CCl4, the mice in the treatment group received BBR intragastrically. In the inhibitor group, besides the injected i.p. with TAA and BBR oral gavage treatment, mice were injected i.p. with a dose of Fer-1 (1 mg/kg/day). Mice were sacrificed under 3% isoflurane anesthesia after 6 weeks of treatment; blood and liver tissue samples were taken and processed for subsequent analyses. At least five mouse hepatic sections were utilized in every group. REF000599 ICD-11: DB93 Liver fibrosis CELL10073; CELL00304; CELL00594; CELL00598 HSC-LX2; LO2; HSC-T6; BRL-3A; GFP-LC3B Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy; Cell proliferation
unique00893 LPIN1 overexpression accelerated iron accumulation, caused lipid peroxidation, reduced GSH and GAPDH, and promoted ferroptotic liver damage in mice after ethanol administration. The study sheds light on potential therapeutic approaches for the prevention and treatment of human alcoholic steatohepatitis. . . . . Driver . The 7-8-month-old male Lpin1-Tg mice and their age-matched littermate wildtype (WT) controls were divided into four dietary groups: (1) WT control, (2) WT plus ethanol (identical to the control diet but with 5% weight per volume ethanol added), (3) Lpin1-Tg control, and (4) Lpin1-Tg plus ethanol. All mice were fed a Lieber-DeCarli liquid diet (BioServ, Frenchtown, NJ) for 5days. Ethanol groups were then fed Lieber-DeCarli liquid diets containing 5% weight per volume ethanol for 10 days while control mice were pairfed to their ethanol-fed counterparts for 10 days. At day 11, mice in the ethanol groups were gavaged a single dose of ethanol (5 g/kg body weight, 31.25% ethanol), whereas mice in control groups were gavaged an isocaloric dose of dextrin maltose. REF000065 ICD-11: DB94 Alcoholic steatohepatitis CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00930 Aberrant liver sirtuin 1 (SIRT1), a mammalian NAD-dependent protein deacetylase, is implicated in the pathogenesis of alcoholic liver disease (ALD).The protective effects of intestinal SIRT1 deficiency are mediated, at least partially, by mitigating hepatic ferroptosis. . . . . Driver . All female mice were first fed a liquid control diet (Lieber-DeCarli formulation; Bioserv, Flemington, NJ) for 5 days. Ethanol groups were then fed a liquid diet containing 5% v/w ethanol for 10 days, whereas control mice were pair-fed to their ethanol-fed counterparts for 10 days. At day 11, the ethanol groups were given a single oral gavage of ethanol (5 g/kg body weight, 31.25% ethanol), whereas WT or SIRT1iKO control mice were given an isocaloric gavage of dextrin maltose. REF000100 ICD-11: DB94 Alcoholic liver disease CELL10130 Liver tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01186 CIRBP promotes ferroptosis by interacting with ELAVL1 and activating ferritinophagy during renal ischaemia-reperfusion (IR) injury. . . . . Driver . Male C57BL/6 mice weighing 20-25 g were subjected to IR as described previously. Renal pedicles were accessed through a midline abdominal incision and clamped for 30 min. Mice body temperature was maintained at 32 throughout the procedure using a heatpad. Clamps were removed and the abdomen was closed after confirmation that blood flow had returned to the kidneys. Reperfusion was allowed to continue for 24 hours. REF000429 ICD-11: DB98 Renal ischemia/reperfusion injury CELL00093 HK2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01126 FAR1 expression is positively correlated with the process of ferroptosis in renal ischemia reperfusion injury (IRI) and tumors. TMEM189, a newly identified gene which introduces vinyl-ether double bond into alkyl-ether lipids to generate plasmalogens abrogates FAR1-alkyl-ether lipids axis induced ferroptosis. . . . . Driver . 8-week old female mice were purchased from Charles River Laboratories and prepared for the establishment of kidney ischemia/reperfusion. The mice were randomly distributed and anaesthetized with subcutaneous injection of sodium pentobarbital (30 mg/kg, Sigma). The heating pads were used to maintain the body temperature. Via the abdominal approach, the bilateral renal pedicles were clamped for 30 min by using a vascular clamp. Then the clamp was removed and the abdominal cavity was closed using sutures. For the group of ferrostatin-1 treatment, mice were injected intraperitoneally 200 ul PBS containing 5 mg/kg ferrostatin-1 30 min before ischemia. REF000360 ICD-11: DB98 Renal ischemia/reperfusion injury CELL00095; CELL00021; CELL00005; CELL00323; CELL00070; CELL00479; CELL00048; CELL00098; CELL00279; CELL00012; CELL00275 HT1080; 786-O; MDA-MB-231; U87MG; A2780; HO8910; HepG2; Hep3B; HuH6; HuH7; Li-7 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01656 miR-199a-5 promotes ferroptosis-induced cardiomyocyte death via the inhibition of AKT/eNOS signaling pathway, thereby contributing to OGD/R injury, suggesting its potential as a target for the development of myocardial ischemia/reperfusion (I/R) injury and focusing on inhibition of miR-199a-5 may be beneficial for attenuating myocardial I/R injury. . . . . Driver . . REF000865 ICD-11: DB98 Myocardial ischemia/reperfusion CELL00030 H9c2 Ferroptosis (hsa04216); PI3K-Akt signaling pathway (hsa04151) Cell ferroptosis
unique01086 FOXC1 transcriptionally activated ELAVL1 may promote ferroptosis during myocardial ischemia and reperfusion (I/R) injury by modulating autophagy, leading to myocardial injury. Inhibition of ELAVL1-mediated autophagic ferroptosis would be a new viewpoint in the treatment of myocardial I/R injury. . . . . Driver . Healthy male C57BL/6J mice (8 weeks) were purchased from Shanghai SLAC laboratory Animal Co., Ltd. (Shanghai, China) and kept in the standard animal facility. To induce myocardial I/R injury, mice were anesthetized by ketamine and xylazine (250 and 10 mg/kg, respectively) first and maintained on 3% isoflurane. An abdominal incision was made around the fourth intercostal space and the left anterior descending coronary artery (LAD) was exposed. LAD was ligated with the silk suture for 1 h followed by 4 h of perfusion. During the perfusion, the incision was closed. For the sham group, same surgery procedures were performed without any ligation. For inhibition of ELAVL1 or overexpression of Beclin-1 in mice, lentivirus vectors (1 x 108 titers) obtained from GeneChem (Shanghai, China) were used for left ventricular cavity injection. After 7 days of lentivirus infection, mice were subjected to myocardial I/R surgery. REF000318 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL10051 Human cardiomyocytes (HCM cells) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01155 In RPTECs, both anoxia and reoxygenation upregulated IDO, which in turn induced GCN2K mediated apoptosis and AhR mediated ferroptosis. Since both phases of IR injury share IDO upregulation as a common point, its inhibition may prove a useful therapeutic strategy for preventing or attenuating ischemia reperfusion injury. . . . . Suppressor . . REF000391 ICD-11: DB98 Ischemia-Reperfusion Injury CELL10147 Renal proximal tubular epithelial cells (RPTECs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00046 The indolylmaleimide (IM) derivativeIM-17shows inhibitory activity against oxidative-stress-induced necrotic cell death and cardioprotective activity in rat ischemia-reperfusion injury models. IM-93 inhibited ferroptosis and NETosis, but not necroptosis or pyroptosis. Suppressor . . . . . . REF000094 ICD-11: DB98 Ischemia-Reperfusion Injury . . Ferroptosis (hsa04216) Cell ferroptosis; NETosis
unique00260 The combination of ponatinib with deferoxamine reduces myocardial ischemia/reperfusion (I/R) injury via simultaneous inhibition of necroptosis and ferroptosis. Suppressor . . . . . Male Sprague-Dawley (SD) rats (250-270 g) were purchased from the Laboratory Animal Center, Xiangya, School of Medicine, Central South University, China. A left thoracotomy was carried out in the fourth intercostal space and the heart was exposed via opening the pericardium. Blockage of the left coronary artery was conducted via clamping the snare against the heart surface. Reperfusion was performed by release of the snare. To establish the I/R injury model, the rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion. REF000350 ICD-11: DB98 Myocardial ischemia/reperfusion injury CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell necroptosis
unique00813 Using liproxstatin-1 (Lip-1) to inhibit ferroptosis during CI could ameliorate LTx- cold ischemia-reperfusion injury, suggesting that Lip-1 administration might be proposed as a new strategy for organ preservation. Suppressor . . . . . All animal procedures were approved and performed according to the protocols established by the Institutional Animal Care and Use Committee of Nanjing Medical University (approval number: 2022; June 2022). Male inbred C57BL/6J mice were purchased from Changzhou Cavans Animal Experiment Co., Ltd (Changzhou, China). Animals were housed in a temperature-controlled (22 ± 2 ) and humidity-controlled room with free access to both fresh water and standard laboratory food in Wuxi Peoples Hospital Animal Experiment Center. Ten- to 12-wk-old animals weighing 25 to 28 g were used for LTx. REF001031 ICD-11: DB98 Cold Ischemia/Reperfusion Injury CELL00076 BEAS-2B Ferroptosis (hsa04216) Cell ferroptosis
unique01490 HPCAL1 as a specific autophagy receptor provides the first mechanistic understanding of how CDH2 is selectively delivered to phagophores, leading to CDH2 degradation for the induction of ferroptosis. The genetic or pharmacological inhibition of HPCAL1 prevented ferroptosis-induced tumor suppression and pancreatitis in suitable mouse models. . . . . Driver . Pancreatic-specific gpx4 knockout mice were produced and identified in our laboratory by crossing floxed Gpx4 (a gift from Dr. Qitao Ran, UT Health San Antonio) and Pdx1-Cre (the Jackson Laboratory, 014647) transgenic mice (C57BL/6J background). For cerulein-induced acute pancreatitis, female mice (8-10 weeks) received seven hourly i.p. injections of 50 ug/kg cerulein in sterile saline. We repeatedly administered iHPCAL1 by i.p. at a dose of 10 mg/kg to mice at 3 and 12 h after the first cerulein injection, while controls were treated by administration with vehicle. The parameters of acute pancreatitis were assessed 12 h after the last cerulein treatment. REF000716 ICD-11: DC31 Pancreatitis CELL00095; CELL00143; CELL00120; CELL00067; CELL00128; CELL00051 HT-1080; Calu-1; PANC1; 5637; SKOV3; PC-3 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique01491 HPCAL1 as a specific autophagy receptor provides the first mechanistic understanding of how CDH2 is selectively delivered to phagophores, leading to CDH2 degradation for the induction of ferroptosis. The genetic or pharmacological inhibition of HPCAL1 prevented ferroptosis-induced tumor suppression and pancreatitis in suitable mouse models. . . . . Suppressor . Pancreatic-specific gpx4 knockout mice were produced and identified in our laboratory by crossing floxed Gpx4 (a gift from Dr. Qitao Ran, UT Health San Antonio) and Pdx1-Cre (the Jackson Laboratory, 014647) transgenic mice (C57BL/6J background). For cerulein-induced acute pancreatitis, female mice (8-10 weeks) received seven hourly i.p. injections of 50 ug/kg cerulein in sterile saline. We repeatedly administered iHPCAL1 by i.p. at a dose of 10 mg/kg to mice at 3 and 12 h after the first cerulein injection, while controls were treated by administration with vehicle. The parameters of acute pancreatitis were assessed 12 h after the last cerulein treatment. REF000716 ICD-11: DC31 Pancreatitis CELL00095; CELL00143; CELL00120; CELL00067; CELL00128; CELL00051 HT-1080; Calu-1; PANC1; 5637; SKOV3; PC-3 Fatty acid metabolism (hsa01212); Autophagy (hsa04140) Cell ferroptosis; Cell autophagy
unique00058 Sodium arsenite-induced ferroptotic cell death is relied on the MtROS-dependent autophagy by regulating the iron homeostasis. Ferroptosis is involved in pancreatic dysfunction triggered by arsenic, and arsenic-induced ferroptosis involves MtROS, autophagy, ferritin. Inducer . . . . . Groups of 18 specific pathogen free (SPF) Adult male Sprague-Dawley rats (300 g -350 g) obtained from Institute of Genome Engineered Animal Models for Human Disease of Dalian Medical University (China). The rats were divided randomly into 3 groups, control, low-dose of NaAsO2 (2.5 mg/kg) and high-dose of NaAsO2 (5 mg/kg), 6 animals in each group. NaAsO2 (CAS No. 7784-46-5) was gained from Sigma Aldrich. The rats were subjected to NaAsO2 at a dose of 0, 2.5 and 5 mg/kg by gavage for 5 months. Control group was given distilled water using the above method. REF000110 ICD-11: DC35 Pancreatic dysfunction CELL00551 MIN6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Autophagy
unique00059 Sodium arsenite-induced ferroptotic cell death is relied on the MtROS-dependent autophagy by regulating the iron homeostasis. Ferroptosis is involved in pancreatic dysfunction triggered by arsenic, and arsenic-induced ferroptosis involves MtROS, autophagy, ferritin. Inducer . . . . . Groups of 18 specific pathogen free (SPF) Adult male Sprague-Dawley rats (300 g -350 g) obtained from Institute of Genome Engineered Animal Models for Human Disease of Dalian Medical University (China). The rats were divided randomly into 3 groups, control, low-dose of NaAsO2 (2.5 mg/kg) and high-dose of NaAsO2 (5 mg/kg), 6 animals in each group. NaAsO2 (CAS No. 7784-46-5) was gained from Sigma Aldrich. The rats were subjected to NaAsO2 at a dose of 0, 2.5 and 5 mg/kg by gavage for 5 months. Control group was given distilled water using the above method. REF000110 ICD-11: DC35 Pancreatic dysfunction CELL00551 MIN6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Autophagy (hsa04140) Cell ferroptosis; Autophagy
unique00957 Ferroptosis contributes to ulcerative colitis (UC) via ER stress-mediated IEC cell death, and that NF-B p65 (RELA) phosphorylation suppresses ER stress-mediated IEC ferroptosis to alleviate UC. . . . . Suppressor . All mice involved had a C57BL/6 gene background. All mice with age- and sex-matched between 6 and 8 weeks of age were assigned randomly to groups. To induce experimental colitis, the mice were challenged with 3% dextran sulfate sodium (DSS; MP Biomedicals, LLC, Solon, OH) in drinking water for 7 days. The control mice were allowed to drink water only at the same time. To administer ferrostatin-1 (Fer1) in vivo, we intraperitoneal injected mice daily with Fer1 (Merck, Darmstadt, Germany, 2.5 umol/kg body weight), and the corresponding control mice were injected intraperitoneally with normal saline. REF000130 ICD-11: DD71 Ulcerative colitis CELL10084 HCoEpiC cell (human normal colonic epithelial cell) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique01697 Ferroptosis is closely associated with the development of ulcerative colitis (UC), and the ferroptosis-related gene ACSF2 can be used as a potential biomarker for the diagnosis and treatment of UC. . . . . Driver . C57BL/6 mice were randomly divided into two groups: control group (n = 7) and DSS group (n = 7). Mice in the DSS group were given 3.0% (w/v) dextran sulfate sodium (DSS, molecular weight, 36-50 kDa; MP Biomedicals, UK) in the drinking water for 7 days. Mice in the control group were fed with normal drinking water throughout the experimental period. REF000916 ICD-11: DD71 Ulcerative colitis CELL00595 IEC-6 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00548 Metformin alleviates the pathological changes of Osteoarthritis by inhibiting ferroptosis in OA chondrocytes, alleviating subchondral sclerosis and reducing abnormal angiogenesis in subchondral bone in advanced OA. Suppressor . . . . . A total of 50 healthy, wild-type adult male C57BL/6 mice (age, 8weeks; weight 20-25 g) were purchased from the Laboratory Animal Center of Ningxia Medical University. After mice were anesthetized with an intraperitoneal injection of 1% sodium pentobarbital (60 mg/kg), the meniscotibial ligament of the right knee was transected to free the anterior crus of the meniscus, and sham surgery was performed without transecting the meniscotibial ligament. Mice were injected intra-articularly with Erastin (15 mg/kg), and the sham and DMM groups were injected with an equal volume of saline twice a week. Moreover, Met was administered by gavage (200 mg/kg/day). Mice were killed by overdose anesthesia 8 weeks after surgery, and the right knee joint was collected for subsequent experiments. REF000766 ICD-11: FA05 Osteoarthritis CELL10129 knee tissues Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01756 Ferroptosis and immune infiltration play an important role in the pathogenesis of intervertebral disc degeneration (IDD). Seven key differentially expressed FRGs (DE-FRGs) were screened, including the upregulated genes NOX4 and PIR, and the downregulated genes TIMM9, ATF3, ENPP2, FADS2 and TFAP2A. . . . . Driver . . REF000982 ICD-11: FA80 Intervertebral disc degeneration CELL10090 Nucleus pulposus cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01820 In Intervertebral disc degeneration (IVDD) cell models, EGR1 knockdown reduced ferroptosis and cartilage degeneration, which was reversed by MAP3K14 overexpression or Erastin treatment. Collectively, EGR1 promoted ferroptosis and IVD cartilage degeneration through MAP3K14-NF-B axis. . . . . Driver . 24 male C57BL/6J mice (8 weeks, weighing 20 ± 2 g) were purchased from Charles River (Beijing, China). Mice were anesthetized via an intraperitoneal injection of 3% pentobarbital sodium (40 mg/kg). Afterward, their extraperitoneal space was isolated and the exterior part of IVD was exposed. A 26 G puncture needle (90% of intervertebral space height) was utilized to punch in the C6/C7 IVD at a depth of 2.5 mm. The puncture needle was inserted into the dorsal annulus fibrosus across the center of the nucleus pulposus and partially across the ventral annulus fibrosus and withdrawn 30 s later. REF001049 ICD-11: FA80 Intervertebral disc degeneration CELL10052 CEP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique01819 In Intervertebral disc degeneration (IVDD) cell models, EGR1 knockdown reduced ferroptosis and cartilage degeneration, which was reversed by MAP3K14 overexpression or Erastin treatment. Collectively, EGR1 promoted ferroptosis and IVD cartilage degeneration through MAP3K14-NF-B axis. . . . . Driver . 24 male C57BL/6J mice (8 weeks, weighing 20 ± 2 g) were purchased from Charles River (Beijing, China). Mice were anesthetized via an intraperitoneal injection of 3% pentobarbital sodium (40 mg/kg). Afterward, their extraperitoneal space was isolated and the exterior part of IVD was exposed. A 26 G puncture needle (90% of intervertebral space height) was utilized to punch in the C6/C7 IVD at a depth of 2.5 mm. The puncture needle was inserted into the dorsal annulus fibrosus across the center of the nucleus pulposus and partially across the ventral annulus fibrosus and withdrawn 30 s later. REF001049 ICD-11: FA80 Intervertebral disc degeneration CELL10052 CEP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); NF-kappa B signaling pathway (hsa04064) Cell ferroptosis
unique01785 Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving intervertebral disc degeneration (IVDD) by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. . . . . Suppressor . 8-10 weeks old male mice were placed in prone position and anesthetized with isoflurane inhalation. The 1.5 cm-long longitudinal incision was made in 2 mm from the posterior midline. The superior and inferior articular processes, supraspinous ligament and interspinous ligament of the L4-L5 lumbar vertebrae were removed to construct LSI, which would induce IVDD. After the operation, the mice were placed in a warm environment. REF001014 ICD-11: FA80 Intervertebral disc degeneration CELL00057; CELL10087 HEK 293T; HNP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01786 Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving intervertebral disc degeneration (IVDD) by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. . . . . Suppressor . 8-10 weeks old male mice were placed in prone position and anesthetized with isoflurane inhalation. The 1.5 cm-long longitudinal incision was made in 2 mm from the posterior midline. The superior and inferior articular processes, supraspinous ligament and interspinous ligament of the L4-L5 lumbar vertebrae were removed to construct LSI, which would induce IVDD. After the operation, the mice were placed in a warm environment. REF001014 ICD-11: FA80 Intervertebral disc degeneration CELL00057; CELL10087 HEK 293T; HNP Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique01685 ART inhibits iron-uptake stimulated osteoclast differentiation by inducing ferroptosis. Artemisinin compounds are potential drugs for treating iron overload-induced osteoporosis. Inducer . . . . . The mice were fed a standard pellet diet (mice maintenance diet; Tengxin Biotechnology Co., Ltd) and distilled water ad libitum and kept at a 12-h lightdark cycle, a temperature of 23 to 25 and a relative humidity of 50% ± 5%. Mice were divided into four groups: control (Ctrl), ferric ammonium citrate (FAC), ART and combined treatment (FAC + ART). FAC (Sigma-Aldrich; 40 mg/kg) were injected intraperitoneally every 3 days for 8 weeks. ART group mice were administered 50 mg/kg by oral gavage every other day for 8 weeks. REF000899 ICD-11: FB83 Osteoporosis CELL00553 RAW264.7 Ferroptosis (hsa04216) Cell ferroptosis
unique01478 Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis. . . . . Suppressor . Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin. REF000710 ICD-11: GA10 Endometriosis CELL10060 Endometrial stromal cells (ESCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01479 Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis. . . . . Driver . Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin. REF000710 ICD-11: GA10 Endometriosis CELL10060 Endometrial stromal cells (ESCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01480 Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/ MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis. . . . . Suppressor . Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin. REF000710 ICD-11: GA10 Endometriosis CELL10060 Endometrial stromal cells (ESCs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00235 Nuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis. Suppressor . . . . . Male C57BL/6 mice (8-10 weeks, 20-25 g) were purchased from HuaFuKang Company (Beijing, China). After 1 week of adaptation to the housing conditions, mice were intraperitoneally injected with folic acid (250 mg/kg) to induce acute kidney injury. An injection of sodium bicarbonate (0.3-M NaHCO3, the vehicle used for folic acid treatment) alone was used as a negative control. Nuciferine (30 mg/kg) was dissolved in water, sonicated, and then immediately administered to mice intragastrically. The sham control mice were treated with nuciferine but not folic acid. REF000303 ICD-11: GB60 Acute kidney injury CELL00093; CELL00057 HK-2; HEK293T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis; Cell proliferation
unique00979 Rheb1 alleviates cisplatin-induced acute kidney injury (AKI) via maintaining mitochondrial homeostasis. Activation of Rheb1 may provide a new therapeutic strategy for AKI. . . . . Suppressor . Homozygous Rheb1 floxed mice (C57BL/6J background) were kindly provided by Dr. Xiao. To induce AKI in mice, Tubule-Rheb1-/-, Tubule-Tsc1+/- and their control littermates aged between 8 and 10 weeks were injected with a single dose of 20 mg/kg cisplatin (cat: P4394, Sigma-Aldrich, St. Louis, MO) intraperitoneally. Mice were sacrificed at day 1, 2 and 3 after cisplatin administration, and mice in AKI models died before being sacrificed were excluded. REF000173 ICD-11: GB60 Acute kidney injury CELL10159 Tubular epithelial cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01239 Both Dpep1 and Chmp1a are important regulators of a single pathway, ferroptosis and lead to acute kidney injury development via altering cellular iron trafficking. . . . . Driver . For FA-induced nephropathy mouse models, 8-week-old male wild-type and Dpep1+/- or Chmp1a+/- mice were injected with FA (250 or 200 mg/kg, dissolved in 300 mM sodium bicarbonate) intraperitoneally and euthanized on day 7. For the cisplatin-induced injury model, 8-week-old male wild-type, Dpep1+/- or Chmp1a+/- mice were injected with cisplatin (25 or 20 mg/kg) intraperitoneally. REF000486 ICD-11: GB60 Acute kidney injury CELL00596 NRK-52E Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01238 Both Dpep1 and Chmp1a are important regulators of a single pathway, ferroptosis and lead to acute kidney injury development via altering cellular iron trafficking. . . . . Suppressor . For FA-induced nephropathy mouse models, 8-week-old male wild-type and Dpep1+/- or Chmp1a+/- mice were injected with FA (250 or 200 mg/kg, dissolved in 300 mM sodium bicarbonate) intraperitoneally and euthanized on day 7. For the cisplatin-induced injury model, 8-week-old male wild-type, Dpep1+/- or Chmp1a+/- mice were injected with cisplatin (25 or 20 mg/kg) intraperitoneally. REF000486 ICD-11: GB60 Acute kidney injury CELL00596 NRK-52E Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00065 Eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00066 Eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00064 Eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00068 Eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00063 Eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00067 Eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00062 Eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00980 Haploinsufficiency for Tsc1 in tubular cells led to Rheb1 activation and mitigated cisplatin-induced cell death, mitochondrial defect and acute kidney injury (AKI). . . . . Driver . To induce AKI in mice, Tubule-Rheb1-/-, Tubule-Tsc1+/-and their control littermates aged between 8 and 10 weeks were injected with a single dose of 20 mg/kg cisplatin (cat: P4394, Sigma-Aldrich, St. Louis, MO) intraperitoneally. Mice were sacrificed at day 1, 2 and 3 after cisplatin administration, and mice in AKI models died before being sacrificed were excluded. REF000173 ICD-11: GB60 Acute kidney injury CELL10159 Tubular epithelial cells Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00061 The study identified eight drugs and hormones that showed antiferroptotic activity, including omeprazole, indole-3-carbinol, rifampicin, promethazine, carvedilol, propranolol, estradiol, and triiodothyronine. Moreover, in mice, the drugs ameliorated acute kidney injury and liver injury, with suppression of tissue lipid peroxidation and decreased cell death. Suppressor . . . . . C57BL/6N male mice (CLEA Japan), aged 8-9 weeks, were used. AKI was induced by intraperitoneal injection of cisplatin solution (16 or 17 mg/kg as indicated; Nichi-Iko Pharmaceutical). Mice were orally treated with water only, promethazine (20 mg/kg in water), or rifampicin (20 mg/kg in 0.5% methylcellulose) every 12 hours for 4 days starting 30 minutes before the cisplatin injection, or orally treated with promethazine (20 mg/kg) in the following groups: (1) no promethazine, (2) pretreatment 30 minutes before cisplatin injection, (3) treatment from 30 minutes before injection to 24 hours after injection, (4) treatment from 24 to 96 hours after injection, and (5) treatment every 12 hours from 30 minutes before injection to 96 hours after injection. REF000116 ICD-11: GB60 Acute kidney injury CELL00030; CELL00603; CELL00093; CELL00546; CELL00005; CELL00596; CELL00606; CELL00120; CELL00549; CELL10103 H9C2; NRK49F; HK2; C2C12; MDA-MB-231; NRK52E; LLC-PK1; Panc-1; HT-22; HUPECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01862 Huaiqihuang has an adjuvant therapeutic effect on kidney disease and even a variety of cancers. Its mechanism includes regulation of oxidative stress, immunity, autophagy, apoptosis, ferroptosis, and pyroptosis. In various kinds of kidney system-related diseases, HQH can effectively reduce hematuria and proteinuria, protect podocytes, regulate cell death, and other functions. The aim is to provide new ideas for the treatment of clinical nephropathy. Inducer . . . . . . REF000198 ICD-11: GB61 Nephropathy . . Apoptosis (hsa04210); Autophagy (hsa04140); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell apoptosis; Cell autophagy; Cell ferroptosis; Cell pyroptosis; Cell clockophagy
unique01621 Calcium oxalate (CaOx) is the most common type of kidney stone. CAV1 could ameliorate autophagy-dependent ferroptosis through the LRP6/Wnt/-Catenin axis, and finally alleviate CaOx stone formation. . . . . Suppressor . Six male SD rats (8 weeks old, 300 g) were purchased from the experimental Animal Centre of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The two groups included control group and the glyoxylic acid group, rats in the glyoxylic acid group were intraperitoneally injected with glyoxylic acid (10.5 mg/ml, 6.66 ml/kg, Macklin, Shanghai, China) every day for 9 days. All rats were given free access to food and maintained in an environment of 25 during the experimental period. 7% chloral hydrate (0.7 ml/100 g) was used for anaesthesia. REF000838 ICD-11: GB70 Kidney calculus CELL00093 HK2 Ferroptosis (hsa04216); Autophagy (hsa04140); Wnt signaling pathway (hsa04310) Cell ferroptosis; Cell autophagy
unique01331 ADPN (ADIPOQ) ameliorated placental injury in gestational diabetes (GDM) by correcting fatty acid oxidation/peroxide imbalance-induced ferroptosis via restoration of CPT-1 activity. . . . . Suppressor . Mice in STZ, HFD + STZ, and HFD/ADN + STZ group were intraperitoneally injected with STZ 40 mg/kg (STZ dissolved in 0.1 mol/L citric acid/sodium citrate buffer) daily for 3 consecutive days and the criteria for successful modeling of GDM were fasting blood glucose >=11.1 mmol/L or random blood glucose >=16.7 mmol/L 72 h after STZ injection. REF000597 ICD-11: JA63 Gestational diabetes CELL00310 HTR-8/SVneoc Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00181 The tocilizumab mimotope vaccination could alleviate renal fibrosis induced by UUO. The mimototpe treatment could reduce the expressions of pro-fibrotic proteins, the activation and differentiations of macrophages and the inhibition of ferroptosis. Suppressor . . . . . Female mice at 6 weeks were bred in SPF facility in Animal Science Center of Hangzhou Normal University. Four groups were set for the next series experiments: the sham group (n = 6 mice), the UUO group (n = 10 mice), the UUO + control peptide group (UUO + CP, n = 10 mice) and the UUO + the Tocilizumab mimotope group (UUO + TM, n = 10 mice). The mimotope vaccinations were performed on days 1, 22 and 43. The UUO was performed on day 51. The mice belonged to the sham group underwent an identical operation except the ligation of the left ureter. All mice were sacrificed on day 65 and the tissue samples were harvested at that time and properly preserved. REF000239 ICD-11: MF54 Renal fibrosis CELL10156 Splenocytes Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
dupunique01184 P53-mediated ferroptosis contributes to the pathogenesis of traumatic brain injury (TBI). Furthermore, SIRT2 exerts a neuroprotective effect against TBI by suppressing p53-mediated ferroptosis. . . . . Driver . The Experimental Animal Center at Southern Medical University provided the wild-type (WT) adult male and female C57BL/6 mice (body weight, 22-25 g). Briefly, mice were anesthetized with an intraperitoneal injection of sodium pentobarbital (30 mg/kg), and mounted on a stereotaxic frame. A midsagittal incision was made in the scalp and a circular craniotomy (4.5 mm diameter) was made over the left parietotemporal cortex. REF000426 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01184 P53-mediated ferroptosis contributes to the pathogenesis of traumatic brain injury (TBI). Furthermore, SIRT2 exerts a neuroprotective effect against TBI by suppressing p53-mediated ferroptosis. . . . . Suppressor . The Experimental Animal Center at Southern Medical University provided the wild-type (WT) adult male and female C57BL/6 mice (body weight, 22-25 g). Briefly, mice were anesthetized with an intraperitoneal injection of sodium pentobarbital (30 mg/kg), and mounted on a stereotaxic frame. A midsagittal incision was made in the scalp and a circular craniotomy (4.5 mm diameter) was made over the left parietotemporal cortex. REF000426 ICD-11: NA07 Traumatic brain injury CELL10005 Brain tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01811 The study identified three immune-mediated ferroptosis genes, namely, Cp, Slc7a11 and Slc39a14, which possibly regulated by neutrophils during the development of acute lung injury, and their pathways may be involved in anti-oxidative stress and anti-lipid metabolism. . . . . Driver . 8- to 10-week-old male C57BL/6 mice were administered 2.5 ug/mL lipopolysaccharide (Escherichia coliserotype 0111: B4) via the trachea. After LPS administration for 6, 12, 24 and 48 h, the mice were euthanized and exsanguinated by cardiac puncture, and the lung tissue was removed for subsequent analysis. REF001043 ICD-11: NB32 Acute lung injury CELL00557 MLE-12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00445 Tyrosine-alanine (YA) had a hepatoprotective effect by reducing inflammation, apoptosis, ferroptosis, and pyroptosis in the LPS/D-GalN-injected ALF mouse model. YA can be used as a functional peptide for the prevention of acute liver injury. Suppressor . . . . . Male C57BL/6 mice (7 weeks old) were purchased from Koatech Co. (Animal Breeding Center, Pyongtaek, Korea). Animals were kept on a 12 h light/dark cycle in a specific pathogen-free area with food and water freely available in the animal facility for 1 week before the experiment. All experimental animals were randomly separated into five groups as follows: Saline, LPS (1 g/kg) + D-GalN (400 mg/kg), LPS/D-GalN + YA (10 mg/kg), LPS/D-GalN + YA (50 mg/kg), and LPS/D-GalN + silymarin (25 mg/kg). YA and silymarin were pre-administered for 10 days before LPS/D-GalN by oral gavage. LPS/D-GalN was injected intraperitoneally. Blood and tissues were collected 6 h after LPS/D-GalN injection. REF000591 ICD-11: NB91 Acute liver injury CELL10130 Liver tissue Fatty acid metabolism (hsa01212); Apoptosis (hsa04210); Ferroptosis (hsa04216); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell pyroptosis
unique00217 Ferroptosis occurred in response to di (2-ethylhexyl) phthalate (DEHP) exposure, which resulted in DEHP-induced liver injury, an enrichment of the ferroptosis pathway along with iron overload, an increase in malondialdehyde (MDA) and lipid peroxidation (LPO) content, and a decrease in glutathione (GSH) levels. Inducer . . . . . Adult male and female fish were randomly assigned to 6 aquariums and acclimated to laboratory conditions for one week before DEHP exposure. There are 6 aquariums, where 3 aquariums were used for DEHP exposure as the treatment groups and 3 for control. Each aquarium was filled with 12 L of artificial seawater and 30 females and 30 males were assigned. Food residues and excrement were removed, and artificial water was renewed every day. The exposure groups were exposed to 10 ug/L DEHP, obtained by diluting the stock solution, and the control groups were treated with DMSO as a solvent control, in which the DMSO content did not exceed 0.01% (v/v). REF000276 ICD-11: NB91 DEHP-induced liver injury CELL10040 Liver tissues Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Glutathione metabolism (hsa00480) Cell ferroptosis
unique01066 Genetic knockout of POR and CYB5R1 decreases cellular hydrogen peroxide generation, preventing lipid peroxidation and ferroptosis. Moreover, POR knockdown in mice confers protective effects during acute liver injury (ALI) caused from ferroptosis. . . . . Driver . Female nu/nu mice aged 4-5 weeks were obtained from Charles River. Luciferase expresing-OVCAR-8 cells were harvested by trypsinization. Subsequently, cells were washed three times with cold PBS and suspended in a 1:1 mixture of PBS and Matrigel (Corning). Each mouse was inoculated subcutaneously with 5 x 106 cells. When tumor volume reached approximately 50 mm3, mice were randomly divided into indicated groups. 20 mg PACMA31 per kg body weight (10% DMSO, 30% PEG-4000, 60% Saline); 40 mg regorafenib per kg body weight (Saline); or 20 mg PACMA31 plus 40 mg regorafenib per kg body weight daily. PACMA31 was intraperitoneally injected and regorafenib was orally administered. REF000284 ICD-11: NB91 Acute liver injury CELL00087; CELL00095; CELL00049; CELL10119; CELL00057; CELL00211 HCT-116; HT-1080; HeLa; MEF; 293T; OVCAR-8 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01065 Genetic knockout of POR and CYB5R1 decreases cellular hydrogen peroxide generation, preventing lipid peroxidation and ferroptosis. Moreover, POR knockdown in mice confers protective effects during acute liver injury (ALI) caused from ferroptosis. . . . . Driver . Female nu/nu mice aged 4-5 weeks were obtained from Charles River. Luciferase expresing-OVCAR-8 cells were harvested by trypsinization. Subsequently, cells were washed three times with cold PBS and suspended in a 1:1 mixture of PBS and Matrigel (Corning). Each mouse was inoculated subcutaneously with 5 x 106 cells. When tumor volume reached approximately 50 mm3, mice were randomly divided into indicated groups. 20 mg PACMA31 per kg body weight (10% DMSO, 30% PEG-4000, 60% Saline); 40 mg regorafenib per kg body weight (Saline); or 20 mg PACMA31 plus 40 mg regorafenib per kg body weight daily. PACMA31 was intraperitoneally injected and regorafenib was orally administered. REF000284 ICD-11: NB91 Acute liver injury CELL00087; CELL00095; CELL00049; CELL10119; CELL00057; CELL00211 HCT-116; HT-1080; HeLa; MEF; 293T; OVCAR-8 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00126 Proanthocyanidins (PACs) treatment significantly decreased the levels of iron, TBARS, ACSL4, and Alox15B, while increased the levels of GSH, GPX4, Nrf2, and HO-1 in traumatic spinal cords. Above all, PACs improved the locomotive function of spinal cord injury (SCI) mice. These results suggest that PACs might be potential therapeutics for SCI repair by inhibiting ferroptosis in SCI. Suppressor . . . . . Female C57BL/6 mice (10-12 weeks old, weighing 24-26 g) were used in this study. Mice were randomly assigned to the following groups: (1) Sham group, subjected to laminectomy operation; (2) SCI group, which underwent SCI with intraperitoneal injection (i.p.) of saline; (3) PACs5 group (5 mg/kg PACs), which underwent SCI with i.p. of 5 mg/kg PACs solved in saline; (4) PACs10 group (10 mg/kg PACs), which underwent SCI with i.p. of 10 mg/kg PACs solutions. REF000185 ICD-11: ND51 Spinal cord injury CELL10156 Spinal cords Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00019 SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after spinal cord injury (SCI). The inflammatory cytokine levels (IL-1, TNF- and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. Suppressor . . . . . Female Wistar rats (n = 120) weighing 240 ± 10 g were purchased from Laboratory Animal Center of the Academy of Military Medical Sciences (Beijing, China). To optimize the SRS 16-86 dose, 20 animals were divided into five groups to test the locomotor recovery at 2 weeks after SCI (n = 4 per group, Sham, SCI-vehicle, 5 mg/kg, 10 mg/kg and 15 mg/kg of SRS 16-86 intraperitoneally). According to the two week preliminary experiments, the dose of 15 mg/kg SRS 16-86 was used in the following experiments. For the TEM observation, 15 animals were divided into five groups (n = 3, Sham, SCI-15min, SCI-1 h, SCI 4 h and SCI 24 h to see the mitochondria changes. Another 9 animals were assigned to detect the TEM of spinal cord at 24 h post injury (n = 3 per group, Sham, SCI-vehicle and SCI-SRS 16-86). 18 animals were used (n = 6 per group, Sham, SCI-vehicle and SCI-SRS 16-86) to observe the hindlimb function at 1 d, 7 d, 14 d, 28 d, 42 d and 56 d after SCI. REF000052 ICD-11: ND51 Spinal cord injury CELL10184 Spinal cord Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00091 Sodium arsenite induced oxidative stress and consequently leading to testicular cell death by ferroptosis. These findings demonstrate a potential beneficial role of supplementation of ferroptosis inhibitors for prevention or treatment of arsenite-related male reproductive toxicity. Inducer . . . . . Specific pathogen free C57BL/6J male mice, aged 7 weeks old, weighted 20-24 g, were provided by Experimental Animal Center of Chongqing Medical University. The animals were adaptive feeding for a week, then randomly divided into four groups: control group, 0.5 mg/L arsenite group, 5 mg/L arsenite group and 50 mg/L arsenite group (n = 8). After exposure of arsenite via drinking water for 6 months, the animals were anesthetized, and the bilateral testicles were immediately separated on ice, weighted and calculated to get viscera coefficient. REF000145 ICD-11: VV5Z Male reproductive toxicity CELL00577 GC-2spd Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00183 CoNPs could induce the ferroptosis-like cell death through the enhancement of intracellular reactive oxygen species (ROS) level, cytoplasmic Fe2+ level, lipid peroxidation, and consumption of reduced glutathione (GSH) as well as inhibition of glutathione peroxidase 4 (GPX4) activity. Importantly, a-lipoic acid (ALA), a natural antioxidant with the capability to scavenge free radicals and chelate toxic metals, was found to efficiently alleviate nanotoxicity. Suppressor . Up regulation . . Suppressor . REF000242 ICD-11: N.A. Nanotoxicity CELL00545 Balb/3T3 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01843 Ardisiacrispin B induced apoptosis in T acute lymphoblastic leukemia CCRFCEM cells via activation of inititator caspases 8 and 9 and effector caspase 3/7, alteration of MMP and increase in ROS production. The diminishment of cytotoxicity by ferrostatin-1 and deferoxamine point to ferroptosis as another mode of cell death in addition to apoptosis. Inducer . . . . . . REF000041 ICD-11: 2A70 T acute lymphoblastic leukemia CELL00080; CELL00005; CELL00087; CELL00323; CELL00048; CELL00541 CCRF-CEM; MDA-MB-231-pcDNA3; HCT116; U87MG; HepG2; AML12 Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01861 Aridanin induced apoptosis in T acute lymphoblastic leukemia CCRF-CEM cells through increase of ROS levels and MMP breakdown, and to a lesser extent via caspases activation. Aridanin also induced ferroptotic and necroptotic cell death. Inducer . . . . . . REF000192 ICD-11: 2A70 T acute lymphoblastic leukemia CELL00080; CELL00087; CELL00295; CELL00005; CELL00048; CELL00541; CELL00601; CELL00542; CELL00007; CELL00154; CELL10080; CELL00499; CELL00330; CELL00609; CELL00502 CCRF-CEM; HCT116; U87; MDA-MB-231; HepG2; AML12; CC531; CLS; B16-F1; B16-F10; A2058; SK-Mel505; MaMel-80a; MV3; SkMel-28; Mel-2A Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necroptosis
unique01849 Ungeremine induced ferroptosis, necroptosis, autophagy as well as apoptosis mediated by caspase activation, MMP alteration and increase ROS production in T acute lymphoblastic leukemia cells. Inducer . . . . . . REF000063 ICD-11: 2A70 T acute lymphoblastic leukemia CELL00080; CELL00005; CELL00087; CELL00323; CELL00048; CELL00541 CCRF-CEM; MDA-MB-231-pcDNA3; HCT116; U87MG; HepG2; AML12 Ferroptosis (hsa04216); Necroptosis (hsa04217); Autophagy (hsa04140); Apoptosis (hsa04210) Cell ferroptosis; Cell necroptosis; Cell autophagy; Cell apoptosis
unique01844 A decrease of cytotoxicity of benzophenone towards T acute lymphoblastic leukemia CCRF-CEM leukemia cells was noted after pre-treatment of cells with two ferroptosis inhibitors, ferrostain-1 and deferoxamine. This shows that ferroptosis is one of the mode of cell death induced by this epunctanone. Inducer . . . . . . REF000048 ICD-11: 2A70 T acute lymphoblastic leukemia CELL00080; CELL00320; CELL00005; CELL00005; CELL00087; CELL00048; CELL00541 CCRF-CEM; CEM/ADR5000; MDA-MB-231-pcDNA3 ; MDA-MB-231-BCRP ; HCT116; HepG2; AML12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique01845 The obtained data highlight the considerable cytotoxic potential of epunctanone and show that this compound induced apoptosis in T acute lymphoblastic leukemia CCRF-CEM cellsviaMMP alterations and increased ROS production. In addition to apoptosis, ferroptosis was also identified as another mode of cell death induced by epunctanone. Inducer . . . . . . REF000048 ICD-11: 2A70 T acute lymphoblastic leukemia CELL00080; CELL00320; CELL00005; CELL00005; CELL00087; CELL00048; CELL00541 CCRF-CEM; CEM/ADR5000; MDA-MB-231-pcDNA3 ; MDA-MB-231-BCRP ; HCT116; HepG2; AML12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00858 ENPP2 overexpression causes upregulation of GPX4 in H9c2 cells. In erastin-induced ferroptosis of H9c2 cells, both NRF2 and ACSL4 are increased, whereas ENPP2 overexpression reduces their expression in erastin-treated H9c2 cells. . . . Down regulation Suppressor Driver . REF000037 ICD-11: N.A. Health CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique00843 64-mediated activation of Src and STAT3 suppresses expression of ACSL4, an enzyme that enriches membranes with long polyunsaturated fatty acids and is required for ferroptosis. . . . Down regulation Suppressor Driver PDX models of triple-negative breast cancer were obtained from the Dana-Farber Cancer Institute and propagated in NSG mice. Tumors were harvested and digested using collagenase at 37. Once digested, the cells were filtered using a cell strainer (40 um), washed twice with PBS, and plated in DMEM/F12 (containing 10% FBS). REF000026 ICD-11: N.A. Health CELL00141; CELL00463; CELL00010 MCF10-A; SUM-159; Hs578T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00844 64-mediated activation of Src and STAT3 suppresses expression of ACSL4, an enzyme that enriches membranes with long polyunsaturated fatty acids and is required for ferroptosis. . . . Down regulation Suppressor Driver PDX models of triple-negative breast cancer were obtained from the Dana-Farber Cancer Institute and propagated in NSG mice. Tumors were harvested and digested using collagenase at 37. Once digested, the cells were filtered using a cell strainer (40 um), washed twice with PBS, and plated in DMEM/F12 (containing 10% FBS). REF000026 ICD-11: N.A. Health CELL00141; CELL00463; CELL00010 MCF10-A; SUM-159; Hs578T Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Apoptosis (hsa04210) Cell ferroptosis; Cell apoptosis
unique00899 The upregulated expression of individual miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b and miR-92 were determined by qRT-PCR. This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. . . . Down regulation Suppressor Driver . REF000069 ICD-11: N.A. Health CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00898 The upregulated expression of individual miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b and miR-92 were determined by qRT-PCR. This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. . . . Down regulation Suppressor Driver . REF000069 ICD-11: N.A. Health CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00897 The upregulated expression of individual miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b and miR-92 were determined by qRT-PCR. This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. . . . Down regulation Suppressor Driver . REF000069 ICD-11: N.A. Health CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00896 The upregulated expression of individual miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b and miR-92 were determined by qRT-PCR. This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. . . . Down regulation Suppressor Driver . REF000069 ICD-11: N.A. Health CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00901 The upregulated expression of individual miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b and miR-92 were determined by qRT-PCR. This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. . . . Down regulation Suppressor Driver . REF000069 ICD-11: N.A. Health CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00900 The upregulated expression of individual miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b and miR-92 were determined by qRT-PCR. This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. . . . Down regulation Suppressor Driver . REF000069 ICD-11: N.A. Health CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00902 The upregulated expression of individual miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b and miR-92 were determined by qRT-PCR. This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20(TNFAIP3)-ACSL4 axis. . . . Up regulation Driver Driver . REF000069 ICD-11: N.A. Health CELL10037 HUVEC Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique01336 MLL4 (KMT2D) deficiency profoundly alters epidermal gene expression and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, and Aloxe3). . . . Up regulation Driver Driver All animal protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania. Mice were maintained on a mixed C57BL/6 background on a standard light-dark cycle. Mice carrying Mll4SET floxed alleles, Mll3SET floxed alleles, or a combination of both of these were crossed with Krt14-Cre transgenic mice. REF000605 ICD-11: N.A. Health CELL00498; CELL00590 NHEK; J2 3T3 fibroblasts Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell differentiation
unique00221 RSL3 induced ROS generation, inhibited CSE/H2S (Hydrogen sulfide) system, damaged mitochondrial structure, increased acetyl-CoA content and lipid peroxidation, which eventually lead to ferroptosis. Supplement of H2S normalized oxidative stress, acetyl-CoA content and ALOX12 acetylation and then protected myoblasts from RSL3-induced ferroptosis. Suppressor . Down regulation . . Driver . REF000281 ICD-11: N.A. Health CELL00546 C2C12 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01337 MLL4 (KMT2D) deficiency profoundly alters epidermal gene expression and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, and Aloxe3). . . . Up regulation Driver Driver All animal protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania. Mice were maintained on a mixed C57BL/6 background on a standard light-dark cycle. Mice carrying Mll4SET floxed alleles, Mll3SET floxed alleles, or a combination of both of these were crossed with Krt14-Cre transgenic mice. REF000605 ICD-11: N.A. Health CELL00498; CELL00590 NHEK; J2 3T3 fibroblasts Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell differentiation
unique00847 PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 (ALOX15) and 15LO2 (ALOX15B) , and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis. . . . Up regulation Driver Driver Male 20 weeks old CD-1 mice were obtained from Charles River Laboratories. The mice were randomly assigned (using random number generator in Excel) to receive 5 mg/kg Fer-1 (Abcam, cat #ab146169) or 1.5% DMSO (vehicle) 60 minutes before injection of folic acid (Sigma-Aldrich) of 250 mg/kg in 0.3 mol/L sodium bicarbonate intraperitoneally. Mice were euthanized 48 h later. REF000028 ICD-11: N.A. Health CELL10048; CELL00549; CELL00093 HAECs; HT22; HK2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00848 PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 (ALOX15) and 15LO2 (ALOX15B) , and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis. . . . Up regulation Driver Driver Male 20 weeks old CD-1 mice were obtained from Charles River Laboratories. The mice were randomly assigned (using random number generator in Excel) to receive 5 mg/kg Fer-1 (Abcam, cat #ab146169) or 1.5% DMSO (vehicle) 60 minutes before injection of folic acid (Sigma-Aldrich) of 250 mg/kg in 0.3 mol/L sodium bicarbonate intraperitoneally. Mice were euthanized 48 h later. REF000028 ICD-11: N.A. Health CELL10048; CELL00549; CELL00093 HAECs; HT22; HK2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00001 Both the 5-LOX inhibitor zileuton and the ferropotosis inhibitor ferrostatin-1 acted through the same cascade to protect against glutamate oxidative toxicity. In conclusion, zileuton protected neurons from glutamate-induced oxidative stress at least in part by inhibiting ferroptosis. Suppressor . Down regulation . . Driver . REF000007 ICD-11: N.A. Health CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01338 MLL4 (KMT2D) deficiency profoundly alters epidermal gene expression and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, and Aloxe3). . . . Up regulation Driver Driver All animal protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Pennsylvania. Mice were maintained on a mixed C57BL/6 background on a standard light-dark cycle. Mice carrying Mll4SET floxed alleles, Mll3SET floxed alleles, or a combination of both of these were crossed with Krt14-Cre transgenic mice. REF000605 ICD-11: N.A. Health CELL00498; CELL00590 NHEK; J2 3T3 fibroblasts Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell differentiation
unique00290 JQ1 treatment reduced the expression of ferroptosis-resistance genes in senescent cells. And the treatment with JQ1 for 48 h showed decreased mRNA expressions of FTH and FTL. JQ1 treatment induced lipid peroxidation in senescent cells but not in non-senescent cells. Inducer . Down regulation . . Suppressor . REF000410 ICD-11: N.A. Health CELL10058 Human dermal fibroblasts (HDFs) Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00856 ENPP2 overexpression causes upregulation of GPX4 in H9c2 cells. In erastin-induced ferroptosis of H9c2 cells, both NRF2 and ACSL4 are increased, whereas ENPP2 overexpression reduces their expression in erastin-treated H9c2 cells. . . . Up regulation Suppressor Suppressor . REF000037 ICD-11: N.A. Health CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique00331 a-Tocopherol, the main component of vitamin E, was shown to rescue the Gpx4-deficient hematopoietic stem and progenitor cells (HSPCs) from ferroptosis in vitro. When Gpx4 knockout mice were fed a vitamin E-depleted diet, a reduced number of HSPCs and impaired function of HSCs were found. Suppressor . Up regulation . . Suppressor C57BL/6 WT mice were purchased from Beijing HFK BioScience Company (Beijing, China). Gpx4flox/flox mice were crossed with Vav-Cre mice and Mx-Cre mice to generate the Gpx4flox/flox Vav-Cre mice and Gpx4flox/flox Mx-Cre mice, respectively. For Gpx4 deletion, Gpx4flox/flox Mx-Cre mice were intraperitoneally injected with 20 mg/kg pIpC (Sigma) every other day for two weeks. CD45.1/45.2 mice and CD45.1 mice on a C57BL/6 background were used as competitor and recipient mice, respectively, in the competitive transplantation assay. Mice were fed natural ingredient diets containing >= 120 IU/kg vitamin E. A fixed formulation diet with or without 75 IU/kg vitamin E (Beijing HFK BioScience Company, Beijing, China) was fed to the mice involved in the vitamin E depletion experiments. For 5-FU treatment, mice were intraperitoneally injected with 150 mg/kg 5-FU (Sigma). REF000453 ICD-11: N.A. Health CELL10123 HSPCs Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00383 Fluvastatin exerts potent protective effects against ox-LDL-induced endothelial cell dysfunction through regulation of GPx4 and xCT. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox-LDL-induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT. Suppressor . Up regulation . . Suppressor . REF000520 ICD-11: N.A. Health CELL10037 HUVECs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00049 Ectopic expression of mutant IDH1 or treatment of cells with cell-permeable D-2-hydroxyglutarate (D-2-HG) promotes the accumulation of lipid reactive oxygen species (ROS) and subsequently ferroptosis. Mechanistically, mutant IDH1 reduces the protein level of the glutathione peroxidase 4 (GPX4). Inducer . Down regulation . . Suppressor . REF000099 ICD-11: N.A. Health CELL00057; CELL00095; CELL00369 HEK293T; HT-1080; KYSE-170 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00050 Ectopic expression of mutant IDH1 or treatment of cells with cell-permeable D-2-hydroxyglutarate (D-2-HG) promotes the accumulation of lipid reactive oxygen species (ROS) and subsequently ferroptosis. Mechanistically, mutant IDH1 reduces the protein level of the glutathione peroxidase 4 (GPX4). . . . Down regulation Driver Suppressor . REF000099 ICD-11: N.A. Health CELL00057; CELL00095; CELL00369 HEK293T; HT-1080; KYSE-170 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00358 The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Suppressor . Up regulation . . Suppressor All mice used in this study were 6-12 weeks old on a C57/BL6/J background. WT or T-KO mice were fed with water supplemented with methionine (1 mgl-1, Sigma) or Se-Met (1 mgl-1, Sigma) and maintained on the diets for 4 weeks before experiments. Alternatively, WT mice were fed with selenium-adequate (0.15 mg/kg) and selenium-high (1 mg/kg) diets that were purchased from Envigo and mice were maintained on the diets for 4 weeks before experiments. REF000485 ICD-11: N.A. Health CELL10157 B cells; T cells Glutathione metabolism (hsa00480); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00857 ENPP2 overexpression causes upregulation of GPX4 in H9c2 cells. In erastin-induced ferroptosis of H9c2 cells, both NRF2 and ACSL4 are increased, whereas ENPP2 overexpression reduces their expression in erastin-treated H9c2 cells. . . . Down regulation Suppressor Marker/Suppressor . REF000037 ICD-11: N.A. Health CELL00030 H9C2 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation; Cell migration
unique01562 Berberine can inhibit erastin-induced ferroptosis in HT22 cells possibly by activating the Nrf2-HO-1/ GPX4 pathway. Suppressor . Up regulation . . Marker/Suppressor . REF000772 ICD-11: N.A. Health CELL00549 HT22 Ferroptosis (hsa04216); Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00958 NRF2 is a known SIAH2 target and master regulator of HO-1 expression. The increased vulnerability of SIAH2 knock-out cells to ferroptosis is probably due to several factors, including the increased expression of pro-ferroptotic HO-1 and the decreased expression of GPX4, a key factor for this iron-catalysed necrotic pathway. . . . Up regulation Suppressor Marker/Suppressor . REF000132 ICD-11: N.A. Health CELL00057; CELL00515; CELL10138 293T; Phoenix ECO; i-MCF Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00886 The activin receptor-like kinase (ALK) 4/5 ( ACVR1B/TGFBR1), also known as activin-transforming growth factor (TGF) receptor, is involved in stress-induced renal injury. Pharmacological inhibition of ALK4/5 signaling attenuated erastin-induced ferroptosis by hyperactivating Nrf2 signaling in HK-2 cells. . . . Down regulation Driver Marker/Suppressor . REF000061 ICD-11: N.A. Health CELL00093 HK-2 Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necrosis
unique00885 The activin receptor-like kinase (ALK) 4/5 (ACVR1B/ TGFBR1), also known as activin-transforming growth factor (TGF) receptor, is involved in stress-induced renal injury. Pharmacological inhibition of ALK4/5 signaling attenuated erastin-induced ferroptosis by hyperactivating Nrf2 signaling in HK-2 cells. . . . Down regulation Driver Marker/Suppressor . REF000061 ICD-11: N.A. Health CELL00093 HK-2 Ferroptosis (hsa04216); Apoptosis (hsa04210); Necroptosis (hsa04217) Cell ferroptosis; Cell apoptosis; Cell necrosis
unique00461 SLC7A11 overexpression significantly rescued the enhanced ferroptosis caused by T-2 toxin. T-2 toxin induces ferroptosis by downregulating SLC7A11 expression. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression. Inducer . Down regulation . . Suppressor . REF000612 ICD-11: N.A. Health CELL00057; CELL00056 HEK293T; H1299 Fatty acid metabolism (hsa01212) Cell ferroptosis
unique00880 Overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner. . . . Up regulation Suppressor Suppressor 5.0 x 106 cells were mixed with Matrigel (BD Biosciences) at 1:1 ratio (v/v) and injected subcutaneously into seven-week old nude mice (NU/NU; Charles River). Mice were fed with regular chow. After nine weeks, the mice were killed and the tumors were weighed and recorded. REF000058 ICD-11: N.A. Health CELL00004; CELL00345; CELL00055; CELL00087; CELL00471; CELL00056; CELL00136; CELL00230; CELL00224 HEK293; SK-N-BE(2)C; U2OS; HCT116; SKRC-42; H1299; T24; UM-UC-3; SW780 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00879 Overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner. . . . Up regulation Suppressor Suppressor 5.0 x 106 cells were mixed with Matrigel (BD Biosciences) at 1:1 ratio (v/v) and injected subcutaneously into seven-week old nude mice (NU/NU; Charles River). Mice were fed with regular chow. After nine weeks, the mice were killed and the tumors were weighed and recorded. REF000058 ICD-11: N.A. Health CELL00004; CELL00345; CELL00055; CELL00087; CELL00471; CELL00056; CELL00136; CELL00230; CELL00224 HEK293; SK-N-BE(2)C; U2OS; HCT116; SKRC-42; H1299; T24; UM-UC-3; SW780 Fatty acid metabolism (hsa01212); Ubiquitin mediated proteolysis (hsa04120) Cell ferroptosis
unique00276 Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK ( MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis. Inducer Up regulation Up regulation . Driver . Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. REF000384 ICD-11: N.A. Health CELL10017 Hippocampal tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
dupunique00276 Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis. Inducer Up regulation . . Driver . Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. REF000384 ICD-11: N.A. Health CELL10017 Hippocampal tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01293 GW501516-activated PPARD stabilized peroxisomes through catalase upregulation by targeting peroxisomal hydrogen peroxide-mediated lysosomal rupture, which led to ferroptosis of xCT-deficient MEFs. Suppressor Up regulation . . Suppressor . . REF000543 ICD-11: N.A. Health CELL10119 MEFs Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique00275 Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK ( MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis. Suppressor Down regulation Down regulation . Driver . Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. REF000384 ICD-11: N.A. Health CELL10017 Hippocampal tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
dupunique00275 Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis. Suppressor Down regulation . . Driver . Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. REF000384 ICD-11: N.A. Health CELL10017 Hippocampal tissue Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01754 EPT1, also termed selenoprotein I (SELENOI), is speculated to directly synthesize phosphatidylethanolamine that drives ferroptosis. It also plays an indispensable role in myelination, neural development and maintaining phospholipid homeostasis in humans. This is consistent with our hypothesis that lowEPT1expression could induce AD through ferroptosis. . . . . Driver . . REF000974 ICD-11: N.A. Health . . Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01854 Acrolein, a lipid peroxide-derived reactive carbonyl species, is involved in plant ferroptosis-like cell death. The acrolein induced cell death could be mitigated by the known ferroptosis inhibitors such as Ferrostatin-1, Deferoxamine, a-Tocopherol, and glutathione. Inducer . . . . . . REF000118 ICD-11: N.A. Health CELL10047 Arabidopsis thalianasuspension cells Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01858 Butein and (S)-butin exert anti-ferroptotic action via an antioxidant pathway (especially the hydrogen atom transfer pathway). And butein displays superior antioxidant or anti-ferroptosis action to (S)-butin. Suppressor . . . . . Sprague-Dawley rats were purchased from the Animal Centre of Guangzhou University of Chinese Medicine. male Sprague-Dawley rats were collected, and the adherent soft tissues were removed. Both ends of the bones were cut away from the diaphysis with bone scissors. The bone marrow plugs were hydrostatically expelled from the bones by insertion of needles fastened to 10-mL syringes filled with complete medium; the needles were inserted into the distal ends of femora and proximal ends of the tibiae, and the marrow plugs expelled from the opposite ends. REF000131 ICD-11: N.A. Health CELL10003 BMSC Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01860 CyPPA rescued the neuronal cells from ferroptosis, while scavenging mitochondrial ROS and inhibiting glycolysis reduced its protection. Furthermore, SK channel activation increased survival of C. elegans challenged with mitochondrial toxins. Suppressor . . . . . The C. elegans strain N2 was grown on NGM plates and on OP50 bacteria as a food source. For the lactate measurement, the nematodes were synchronized by bleaching with NaOH/NaClO and grown on NGM plates containing OP50 and either DMSO, 100 uM CyPPA or 250 uM CyPPA for 4 days. To determine lactate levels, the lactate assay kit was used (Sigma-Aldrich, MAK064). Briefly, worms were collected and washed to remove OP50. The worm pellet was snap-frozen, resuspended in lactate assay buffer and sonicated to break the cuticle. After centrifugation at 13000 rpm for 10 min, the supernatant was applied to a 10 kDa MWCO filter and centrifuged for 60 min at 13000 rpm to remove insoluble material. REF000166 ICD-11: N.A. Health CELL00549 HT22 Fatty acid metabolism (hsa01212); Gluconeogenesis (hsa00010) Cell ferroptosis
unique01867 Geraniin exhibits ferroptosis-inhibitory potential towards erastin-treated bmMSCs; such potential may mainly stem from its strong lipid peroxidation (LPO)-inhibition, Fe2+-chelating, and antioxidant actions. Geraniin gives neither dimer nor radical adduct, owing to the bulky HHDP (or DHHDP) group; thus, it is considered as a safe and effective ferroptosis-inhibitor. Suppressor . . . . . . REF000325 ICD-11: N.A. Health CELL10165 bmMSCs Ferroptosis (hsa04216) Cell ferroptosis
unique00379 Ze 450 regulated HIF1 and cMyc protein levels in a shifted time dependency, which finally led to an enhanced glycolytic metabolism, by increasing HXKII and PDK1 protein levels. The protective effects against ferroptosis were mediated independently of estrogen receptor activation and were distinct from effects exerted by metformin. Suppressor . Up regulation . . . . REF000515 ICD-11: N.A. Health CELL00549 HT22 Fatty acid metabolism (hsa01212); Gluconeogenesis (hsa00010) Cell ferroptosis
unique01857 Butein and (S)-butin exert anti-ferroptotic action via an antioxidant pathway (especially the hydrogen atom transfer pathway). And butein displays superior antioxidant or anti-ferroptosis action to (S)-butin. Suppressor . . . . . Sprague-Dawley rats were purchased from the Animal Centre of Guangzhou University of Chinese Medicine. male Sprague-Dawley rats were collected, and the adherent soft tissues were removed. Both ends of the bones were cut away from the diaphysis with bone scissors. The bone marrow plugs were hydrostatically expelled from the bones by insertion of needles fastened to 10-mL syringes filled with complete medium; the needles were inserted into the distal ends of femora and proximal ends of the tibiae, and the marrow plugs expelled from the opposite ends. REF000131 ICD-11: N.A. Health CELL10003 BMSC Fatty acid metabolism (hsa01212) Cell ferroptosis
unique01863 Measures of lipid peroxidation and cell death show an increase with age and reduction by both Lip-1 and salicylaldehyde isonicotinoyl hydrazone (SIH) treatment. Blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan. Suppressor . . . . . A synchronous population was obtained by transferring egg-laying adults to fresh plates at 16 for 2-3 hr. The adults were removed and the plates with eggs then transferred to 25 to ensure sterility. After 48 hr at 25, when worms were at the late L4/young adult stage, 25-35 nematodes were transferred to fresh plates containing either vehicle control, 250 uM SIH, or 200 uM Lip-1. All plates were coded to allowing blinding of the experimenter to the treatment regime during scoring. REF000201 ICD-11: N.A. Health . . Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01855 The widely used sulfation inhibitor sodium chlorate and b-d-xyloside, which prevents proteoglycan glycosaminoglycan chain attachment, both reduced HS and CS, and exacerbated glutamate- and erastin-induced cell death, suggesting that extracellular matrix influenced oxytosis and ferroptosis. Inducer . . . . . . REF000125 ICD-11: N.A. Health CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01856 The widely used sulfation inhibitor sodium chlorate and b-d-xyloside, which prevents proteoglycan glycosaminoglycan chain attachment, both reduced HS and CS, and exacerbated glutamate- and erastin-induced cell death, suggesting that extracellular matrix influenced oxytosis and ferroptosis. Inducer . . . . . . REF000125 ICD-11: N.A. Health CELL00549 HT22 Fatty acid metabolism (hsa01212); Ferroptosis (hsa04216) Cell ferroptosis
unique01851 There is no excess ROS in discs with reducedwtsactivity, but ifFer1HCHis knocked-down simultaneously, very high ROS levels accumulate in the tissue, suggesting a protective role for the excess Fer1HCH inwtsmutants. . . . . Suppressor . . REF000098 ICD-11: N.A. Health . . Ferroptosis (hsa04216) Cell ferroptosis; Cell proliferation
unique00336 Two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Suppressor . . . . . Sprague-Dawley rats (4 weeks) were obtained from the Animal Center of the Guangzhou University of Chinese Medicine. Procurement, maintenance, and treatment of the animals were performed under the supervision of the Institutional Animal Ethics Committee of the Guangzhou University of Chinese Medicine. The Gaussian 16 C.01 program was purchased from Guangzhou Molcalx Ltd. (Guangzhou, China). REF000462 ICD-11: N.A. Health CELL10164 Bone marrow mesenchymal stem cells(BMMSCs) Ferroptosis (hsa04216) Cell ferroptosis
unique00335 Two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Suppressor . . . . . Sprague-Dawley rats (4 weeks) were obtained from the Animal Center of the Guangzhou University of Chinese Medicine. Procurement, maintenance, and treatment of the animals were performed under the supervision of the Institutional Animal Ethics Committee of the Guangzhou University of Chinese Medicine. The Gaussian 16 C.01 program was purchased from Guangzhou Molcalx Ltd. (Guangzhou, China). REF000462 ICD-11: N.A. Health CELL10164 Bone marrow mesenchymal stem cells(BMMSCs) Ferroptosis (hsa04216) Cell ferroptosis