General Information of the Disease (ID: DIS00040)
Name
Ovarian cancer
ICD
ICD-11: 2C73
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.

    Click to Show/Hide
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
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
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
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.

    Click to Show/Hide
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.

    Click to Show/Hide
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.

    Click to Show/Hide
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.

    Click to Show/Hide
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
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Ref 2 A TAZ-ANGPTL4-NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer. Mol Cancer Res. 2020 Jan;18(1):79-90. doi: 10.1158/1541-7786.MCR-19-0691. Epub 2019 Oct 22.
Ref 3 Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer. Front Pharmacol. 2021 May 26;12:681223. doi: 10.3389/fphar.2021.681223. eCollection 2021.
Ref 4 Ropivacaine represses the ovarian cancer cell stemness and facilitates cell ferroptosis through inactivating the PI3K/AKT signaling pathway. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221120652. doi: 10.1177/09603271221120652.
Ref 5 Apatinib combined with olaparib induces ferroptosis via a p53-dependent manner in ovarian cancer. J Cancer Res Clin Oncol. 2023 Sep;149(11):8681-8689. doi: 10.1007/s00432-023-04811-1. Epub 2023 Apr 29.
Ref 6 MeninMLL inhibitors induce ferroptosis and enhance the antiproliferative activity of auranofin in several types of cancer cells. Int J Oncol. 2020 Oct;57(4):1057-1071. doi: 10.3892/ijo.2020.5116. Epub 2020 Aug 28.
Ref 7 Norcantharidin induces ferroptosis via the suppression of NRF2/HO-1 signaling in ovarian cancer cells. Oncol Lett. 2022 Aug 25;24(4):359. doi: 10.3892/ol.2022.13479. eCollection 2022 Oct.
Ref 8 Tripterygium glycosides reverse chemotherapy resistance in ovarian cancer by targeting the NRF2/GPX4 signal axis to induce ferroptosis of drug-resistant human epithelial ovarian cancer cells. Biochem Biophys Res Commun. 2023 Jul 12;665:178-186. doi: 10.1016/j.bbrc.2023.04.111. Epub 2023 Apr 29.
Ref 9 MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Nov 28;47(11):1512-1521. doi: 10.11817/j.issn.1672-7347.2022.210800.
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Ref 11 Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4. Neoplasma. 2021 Jan;68(1):165-173. doi: 10.4149/neo_2020_200707N705. Epub 2020 Oct 7.
Ref 12 Long non-coding RNA ADAMTS9-AS1 attenuates ferroptosis by Targeting microRNA-587/solute carrier family 7 member 11 axis in epithelial ovarian cancer. Bioengineered. 2022 Apr;13(4):8226-8239. doi: 10.1080/21655979.2022.2049470.
Ref 13 circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis. BMB Rep. 2023 Mar;56(2):184-189. doi: 10.5483/BMBRep.2022-0175.
Ref 14 CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14(ARF) degradation. Cell Death Differ. 2022 Apr;29(4):758-771. doi: 10.1038/s41418-021-00890-0. Epub 2021 Nov 6.
Ref 15 PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer. Redox Biol. 2021 Jun;42:101928. doi: 10.1016/j.redox.2021.101928. Epub 2021 Mar 5.
Ref 16 GALNT14 regulates ferroptosis and apoptosis of ovarian cancer through theEGFR/mTOR pathway. Future Oncol. 2022 Jan;18(2):149-161. doi: 10.2217/fon-2021-0883. Epub 2021 Oct 13.
Ref 17 PML-Regulated Mitochondrial Metabolism Enhances Chemosensitivity in Human Ovarian Cancers. Cell Metab. 2019 Jan 8;29(1):156-173.e10. doi: 10.1016/j.cmet.2018.09.002. Epub 2018 Sep 20.
Ref 18 Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma. Front Oncol. 2022 Oct 5;12:1021558. doi: 10.3389/fonc.2022.1021558. eCollection 2022.