Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00040)
Name |
Ovarian cancer
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ICD |
ICD-11: 2C73
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Full List of Target(s) of This Ferroptosis-centered Disease
Stearoyl-CoA desaturase (SCD)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | NL01 | Investigative | |||
Responsed Regulator | Hydroxycarboxylic acid receptor 1 (HCAR1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
AMPK signaling pathway | hsa04152 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | Anglne cells | Ovarian carcinoma | Homo sapiens | CVCL_U287 | |
HO8910PM cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0310 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | NL01 | Investigative | |||
Responsed Regulator | Sterol regulatory element-binding protein 1 (SREBF1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
AMPK signaling pathway | hsa04152 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | Anglne cells | Ovarian carcinoma | Homo sapiens | CVCL_U287 | |
HO8910PM cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0310 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [6] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | High grade ovarian serous adenocarcinoma [ICD-11: 2C73] | ||||
Responsed Drug | MI463 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | OVCAR-8 cells | High grade ovarian serous adenocarcinoma | Homo sapiens | CVCL_1629 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
OVCAR-4 cells | Ovarian adenocarcinoma | Homo sapiens | CVCL_1627 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
Lu-99 cells | Lung giant cell carcinoma | Homo sapiens | CVCL_3015 | ||
Lu-65 cells | Lung giant cell carcinoma | Homo sapiens | CVCL_1392 | ||
PC-7 cells | Lung adenocarcinoma | Homo sapiens | CVCL_A786 | ||
BT-549 cells | Invasive breast carcinoma | Homo sapiens | CVCL_1092 | ||
MDA-MB-468 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0419 | ||
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | ||
MCF-7 cells | Breast carcinoma | Homo sapiens | CVCL_0031 | ||
T-47D cells | Invasive breast carcinoma | Homo sapiens | CVCL_0553 | ||
MIA PaCa-2 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0428 | ||
PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | ||
BxPC-3 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0186 | ||
CFPAC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_1119 | ||
Response regulation | 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. | ||||
Cytochrome b-245 heavy chain (CYBB)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | |||
Target for Ferroptosis | Driver | |||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | |||
Responsed Drug | Carboplatin | Investigative | ||
Responsed Regulator | WW domain-containing transcription regulator protein 1 (WWTR1) | Driver | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Hippo signaling pathway | hsa04390 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model | Caov-2 cells | Ovarian carcinoma | Homo sapiens | CVCL_6861 |
TOV-21G cells | Ovarian clear cell adenocarcinoma | Homo sapiens | CVCL_3613 | |
Response regulation | 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. | |||
Cystine/glutamate transporter (SLC7A11)
In total 20 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Lidocaine | Investigative | |||
Responsed Regulator | hsa-miR-382-5p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell proliferation | |||||
Cell migration | |||||
Cell invasion | |||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
T-47D cells | Invasive breast carcinoma | Homo sapiens | CVCL_0553 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Norcantharidin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Epithelial ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | ADAMTS9-AS1 (IncRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
In Vitro Model | ES-2 cells | Ovarian clear cell adenocarcinoma | Homo sapiens | CVCL_3509 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Caov-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0201 | ||
Response regulation | ADAMTS9-AS1 regulated SLC7A11 expression through miR-587, thereby affecting ferroptosis, proliferation and migration of Epithelial ovarian cancer cells. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [13] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | CircSnx12 (circRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
Response regulation | 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. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [14] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Kelch domain-containing protein 3 | Suppressor | |||
Pathway Response | Ubiquitin mediated proteolysis | hsa04120 | |||
Fatty acid metabolism | hsa01212 | ||||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
Cell growth | |||||
In Vitro Model | HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | |
NCI-H1299 cells | Lung large cell carcinoma | Homo sapiens | CVCL_0060 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
SJSA-1 cells | Osteosarcoma | Homo sapiens | CVCL_1697 | ||
HeLa cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
Huh-7 cells | Hepatocellular carcinoma | Homo sapiens | CVCL_0336 | ||
MCF-7 cells | Breast carcinoma | Homo sapiens | CVCL_0031 | ||
A-549 cells | Lung adenocarcinoma | Homo sapiens | CVCL_0023 | ||
Hep 3B2.1-7 cells | Hepatocellular carcinoma | Homo sapiens | CVCL_0326 | ||
CT26 cells | Colon adenocarcinoma | Mus musculus | CVCL_7254 | ||
L-02 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | ||
HCCLM3 cells | Adult hepatocellular carcinoma | Homo sapiens | CVCL_6832 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [12] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Epithelial ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | hsa-miR-587 (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
In Vitro Model | ES-2 cells | Ovarian clear cell adenocarcinoma | Homo sapiens | CVCL_3509 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Caov-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0201 | ||
Response regulation | ADAMTS9-AS1 regulated SLC7A11 expression through miR-587, thereby affecting ferroptosis, proliferation and migration of Epithelial ovarian cancer cells. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [13] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | hsa-miR-194-5p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
Response regulation | 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. | ||||
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Poly [ADP-ribose] polymerase 1 (PARP1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 9 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP10 (PARP10) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 10 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP11 (PARP11) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 11 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP12 | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 12 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP14 | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
Click to Show/Hide
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Response regulation | 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. | ||||
Experiment 13 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP15 | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
Click to Show/Hide
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Response regulation | 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. | ||||
Experiment 14 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP16 | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
Click to Show/Hide
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Response regulation | 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. | ||||
Experiment 15 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Poly [ADP-ribose] polymerase 2 (PARP2) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 16 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP3 (PARP3) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 17 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP4 (PARP4) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 18 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP6 (PARP6) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 19 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP8 (PARP8) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 20 Reporting the Ferroptosis-centered Disease Response by This Target | [15] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein mono-ADP-ribosyltransferase PARP9 (PARP9) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | HEY cells | Ovarian carcinoma | Homo sapiens | CVCL_0297 | |
A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Unspecific Target
In total 7 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Ropivacaine | Approved | |||
Responsed Regulator | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) | Suppressor | |||
Pathway Response | PI3K-Akt signaling pathway | hsa04151 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [4] | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Ropivacaine | Approved | |||
Responsed Regulator | RAC-alpha serine/threonine-protein kinase (AKT1) | Suppressor | |||
Pathway Response | PI3K-Akt signaling pathway | hsa04151 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Apatinib | Investigative | |||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Response regulation | 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. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Olaparib | Investigative | |||
Responsed Regulator | Cellular tumor antigen p53 (TP53) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Response regulation | 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. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [16] | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
OVISE cells | Ovarian clear cell adenocarcinoma | Homo sapiens | CVCL_3116 | ||
Response regulation | 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. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [17] | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Protein PML (PML) | Suppressor | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Gluconeogenesis | hsa00010 | ||||
Oxidative phosphorylation | hsa00190 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OV-90 cells | Ovarian adenocarcinoma | Homo sapiens | CVCL_3768 | ||
Caov-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0201 | ||
OV7 cells | Ovarian carcinoma | Homo sapiens | CVCL_2675 | ||
COV504 cells | Ovarian carcinoma | Homo sapiens | CVCL_2424 | ||
OV56 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_2673 | ||
OVCAR-8 cells | High grade ovarian serous adenocarcinoma | Homo sapiens | CVCL_1629 | ||
OC 314 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_1616 | ||
KURAMOCHI cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_1345 | ||
OVSAHO cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_3114 | ||
OVCAR-4 cells | Ovarian adenocarcinoma | Homo sapiens | CVCL_1627 | ||
FU-OV-1 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_2047 | ||
COV318 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_2419 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [18] | ||||
Responsed Disease | Ovarian serous cystadenocarcinoma [ICD-11: 2C73] | ||||
Responsed Regulator | Peregrin (BRPF1) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Gluconeogenesis | hsa00010 | ||||
Wnt signaling pathway | hsa04310 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
Response regulation | 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. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 8 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Apatinib | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Response regulation | 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. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Norcantharidin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Olaparib | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Response regulation | 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. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Triptolide | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | A2780/DDP cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_D619 | |
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Frizzled-7 (FZD7) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HOSE 96-9-98 cells | Normal | Homo sapiens | CVCL_UW70 | |
HO8910 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6868 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
Response regulation | 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. | ||||
Experiment 6 Reporting the Ferroptosis-centered Disease Response by This Target | [9] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | hsa-miR-1-3p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | HOSE 96-9-98 cells | Normal | Homo sapiens | CVCL_UW70 | |
HO8910 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6868 | ||
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
Response regulation | 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. | ||||
Experiment 7 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Frizzled-7 (FZD7) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
OVCAR5 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_1628 | ||
COV362 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_2420 | ||
FT190 cells | Normal | Homo sapiens | CVCL_UH57 | ||
PEO1 cells | Metastasis of ovarian carcinoma | Homo sapiens | CVCL_2686 | ||
PEO4 cells | Ovarian cystadenocarcinoma | Homo sapiens | CVCL_2690 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 8 Reporting the Ferroptosis-centered Disease Response by This Target | [10] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Regulator | Tumor protein 63 (TP63) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
OVCAR5 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_1628 | ||
COV362 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_2420 | ||
FT190 cells | Normal | Homo sapiens | CVCL_UH57 | ||
PEO1 cells | Metastasis of ovarian carcinoma | Homo sapiens | CVCL_2686 | ||
PEO4 cells | Ovarian cystadenocarcinoma | Homo sapiens | CVCL_2690 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 4 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Apatinib | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Response regulation | 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. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Norcantharidin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [5] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Olaparib | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
Cell autophagy | |||||
In Vitro Model | A2780 cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_0134 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
Response regulation | 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. | ||||
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target | [8] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Triptolide | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | A2780/DDP cells | Ovarian endometrioid adenocarcinoma | Homo sapiens | CVCL_D619 | |
In Vivo Model |
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.
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Response regulation | 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. | ||||
Monocarboxylate transporter 1 (SLC16A1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | NL01 | Investigative | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
AMPK signaling pathway | hsa04152 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model | Anglne cells | Ovarian carcinoma | Homo sapiens | CVCL_U287 | |
HO8910PM cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_0310 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
In total 1 item(s) under this target | ||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [11] | |||
Target for Ferroptosis | Driver | |||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | |||
Responsed Regulator | hsa-miR-424-5p (miRNA) | Suppressor | ||
Pathway Response | Fatty acid metabolism | hsa01212 | ||
Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | |||
In Vitro Model | HO8910 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6868 |
SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
Response regulation | 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. | |||
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [7] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Ovarian cancer [ICD-11: 2C73] | ||||
Responsed Drug | Norcantharidin | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | SK-OV-3 cells | Ovarian serous cystadenocarcinoma | Homo sapiens | CVCL_0532 | |
OVCAR-3 cells | Ovarian serous adenocarcinoma | Homo sapiens | CVCL_0465 | ||
In Vivo Model |
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.
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Response regulation | 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. | ||||
References