Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10154)
Regulator Name Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)
Synonyms
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha; Phosphoinositide 3-kinase alpha; Phosphoinositide-3-kinase catalytic alpha polypeptide; Serine/threonine protein kinase PIK3CA
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Gene Name PIK3CA
Gene ID 5290
Regulator Type Protein coding
Uniprot ID P42336
Sequence
MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQ
LLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFA
IGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKH
IYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLK
LCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMD
CFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGI
YHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHC
PLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWF
SSVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPL
SEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAME
LLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTN
QRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILK
QEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLW
LNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLS
IGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRS
CAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDF
LIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIA
YIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALN

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Family PI3/PI4-kinase family
Function
Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain- containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others. Plays a role in the positive regulation of phagocytosis and pinocytosis.

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HGNC ID
HGNC:8975
KEGG ID hsa:5290
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PIK3CA can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Browse Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Responsed Drug Curcumin Investigative
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 HCT-8 cells Ileocecal adenocarcinoma Homo sapiens CVCL_2478
Response regulation Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Cardiomyopathy ICD-11: BC43
 Disease Info 
Responsed Drug Lapatinib Investigative
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model
 CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
Response regulation Lapatinib (LAP) inhibited the cell viability and exacerbated cell injury induced by doxorubicin, as well as increased cell apoptosis. LAP aggravated Dox-induced cardiotoxicity by promoting oxidative stress and ferroptosis in cardiomyocytes via PI3K/AKT-mediated mitochondrial dysfunction. Moreover, GPX4 expression was decreased and ASCL4 level was higher following DOX treatment or the combination therapy of LAP and DOX.
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [3]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Parkinson disease ICD-11: 8A00
 Disease Info 
Responsed Drug Thioctic acid Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 PC12 cells Adrenal gland pheochromocytoma Rattus norvegicus CVCL_0481
Response regulation a-Lipoic acid (a-LA) suppressed cell viability decline and mitigated ferroptosis in an MPP-induced PC12 cell model of parkinson's disease (PD) via activating the PI3K/Akt/Nrf2 pathway. These results discovered a novel a-LA-based therapy for PD patients, and activating the PI3K/Akt/Nrf2 pathway might be developed as a promising therapeutic approach for PD.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [5]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice weighing between 20 and 23 g were selected and 5 x 106 Hep-G2 cells were subcutaneously injected into their backs. The mice were subsequently divided into the following four groups: control (n = 5), FNDC5 overexpressing (n = 5), FNDC5 overexpressing followed by treatment with the PI3K inhibitor LY294002 (MCE, China), and FNDC5 knockdown (n = 5). Seven days after cell injection, sorafenib (30 mg/kg) was administered to all mice via intraperitoneal injection every alternate day for 4 weeks. The mice in the third group were intraperitoneally injected with LY294002 (25 mg/kg) diluted with DMSO twice a week for 4 weeks.

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Response regulation FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response in Hepatocellular Carcinoma Cells, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [4]
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Responsed Drug Ropivacaine Approved
 Drug Info 
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 Target of This Regulator [6]
Responsed Disease Nervous system disease ICD-11: 8E7Z
 Disease Info 
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Necroptosis hsa04217
Citrate cycle hsa00020
Cell Process Cell ferroptosis
Cell apoptosis
Cell necrosis
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
661W cells Normal Mus musculus CVCL_6240
RGC-5 cells Normal Mus musculus CVCL_4059
C6 cells Malignant glioma Rattus norvegicus CVCL_0194
In Vivo Model
Whole cerebral neocortices were removed from the rat fetuses, and incubated in 0.03% trypsin in Earles balanced salt solution (EBSS) without Ca2 + or Mg2 + for 90 min at 37. Subsequently, the cortices washed with fresh EBSS, transferred into culture medium (12.5% F-12 growth media (Sigma), 12.5% heat inactivated horse serum (Hyclone), 30 U/ml Penicillin, 0.03 mg/ml Streptomycin solution (both Sigma), 2.5 mM glutamine (Sigma), 10 mM HEPES (Omega) in DMEM with high glucose (4500 g/l, Sigma) and dissociated by trituration.

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Response regulation Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases. The PI3K (PIK3CA) inhibitor protects cells by inducing partial restoration of depleted glutathione levels and accumulation of intracellular amino acids, whereas the Flt3 inhibitor prevents lipid peroxidation, a key mechanism of glutamate-mediated toxicity.
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) Protein coding
 Regulator Info 
Responsed Drug Curcumin Investigative
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 HCT-8 cells Ileocecal adenocarcinoma Homo sapiens CVCL_2478
Response regulation Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway.
Parkinson disease [ICD-11: 8A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) Protein coding
 Regulator Info 
Responsed Drug Thioctic acid Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 PC12 cells Adrenal gland pheochromocytoma Rattus norvegicus CVCL_0481
Response regulation a-Lipoic acid (a-LA) suppressed cell viability decline and mitigated ferroptosis in an MPP-induced PC12 cell model of parkinson's disease (PD) via activating the PI3K/Akt/Nrf2 pathway. These results discovered a novel a-LA-based therapy for PD patients, and activating the PI3K/Akt/Nrf2 pathway might be developed as a promising therapeutic approach for PD.
Cardiomyopathy [ICD-11: BC43]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) Protein coding
 Regulator Info 
Responsed Drug Lapatinib Investigative
 Drug Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model
 CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
Response regulation Lapatinib (LAP) inhibited the cell viability and exacerbated cell injury induced by doxorubicin, as well as increased cell apoptosis. LAP aggravated Dox-induced cardiotoxicity by promoting oxidative stress and ferroptosis in cardiomyocytes via PI3K/AKT-mediated mitochondrial dysfunction. Moreover, GPX4 expression was decreased and ASCL4 level was higher following DOX treatment or the combination therapy of LAP and DOX.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [5]
Target Regulator Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) Protein coding
 Regulator Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Mice weighing between 20 and 23 g were selected and 5 x 106 Hep-G2 cells were subcutaneously injected into their backs. The mice were subsequently divided into the following four groups: control (n = 5), FNDC5 overexpressing (n = 5), FNDC5 overexpressing followed by treatment with the PI3K inhibitor LY294002 (MCE, China), and FNDC5 knockdown (n = 5). Seven days after cell injection, sorafenib (30 mg/kg) was administered to all mice via intraperitoneal injection every alternate day for 4 weeks. The mice in the third group were intraperitoneally injected with LY294002 (25 mg/kg) diluted with DMSO twice a week for 4 weeks.

    Click to Show/Hide
Response regulation FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response in Hepatocellular Carcinoma Cells, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [4]
Target Regulator Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) Protein coding
 Regulator Info 
Responsed Drug Ropivacaine Approved
 Drug Info 
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.

    Click to Show/Hide
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.
Nervous system disease [ICD-11: 8E7Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [6]
Target Regulator Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Necroptosis hsa04217
Citrate cycle hsa00020
Cell Process Cell ferroptosis
Cell apoptosis
Cell necrosis
In Vitro Model
 HT22 cells Normal Mus musculus CVCL_0321
661W cells Normal Mus musculus CVCL_6240
RGC-5 cells Normal Mus musculus CVCL_4059
C6 cells Malignant glioma Rattus norvegicus CVCL_0194
In Vivo Model
Whole cerebral neocortices were removed from the rat fetuses, and incubated in 0.03% trypsin in Earles balanced salt solution (EBSS) without Ca2 + or Mg2 + for 90 min at 37. Subsequently, the cortices washed with fresh EBSS, transferred into culture medium (12.5% F-12 growth media (Sigma), 12.5% heat inactivated horse serum (Hyclone), 30 U/ml Penicillin, 0.03 mg/ml Streptomycin solution (both Sigma), 2.5 mM glutamine (Sigma), 10 mM HEPES (Omega) in DMEM with high glucose (4500 g/l, Sigma) and dissociated by trituration.

    Click to Show/Hide
Response regulation Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases. The PI3K (PIK3CA) inhibitor protects cells by inducing partial restoration of depleted glutathione levels and accumulation of intracellular amino acids, whereas the Flt3 inhibitor prevents lipid peroxidation, a key mechanism of glutamate-mediated toxicity.
Thioctic acid [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [3]
Drug for Ferroptosis Suppressor
Response Target Nuclear factor erythroid 2-related factor 2 (NFE2L2) Suppressor; Marker
 Target Info 
Responsed Disease Parkinson disease ICD-11: 8A00
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 PC12 cells Adrenal gland pheochromocytoma Rattus norvegicus CVCL_0481
Response regulation a-Lipoic acid (a-LA) suppressed cell viability decline and mitigated ferroptosis in an MPP-induced PC12 cell model of parkinson's disease (PD) via activating the PI3K/Akt/Nrf2 pathway. These results discovered a novel a-LA-based therapy for PD patients, and activating the PI3K/Akt/Nrf2 pathway might be developed as a promising therapeutic approach for PD.
Curcumin [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
 Target Info 
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 HCT-8 cells Ileocecal adenocarcinoma Homo sapiens CVCL_2478
Response regulation Treating HCT-8 cells with curcumin significantly downregulated GSH, SLC7A11, and GPX4, while significantly increasing levels of iron, MDA, and ROS. Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway.
Lapatinib [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [2]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
 Target Info 
Responsed Disease Cardiomyopathy ICD-11: BC43
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
In Vitro Model
 CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
Response regulation Lapatinib (LAP) inhibited the cell viability and exacerbated cell injury induced by doxorubicin, as well as increased cell apoptosis. LAP aggravated Dox-induced cardiotoxicity by promoting oxidative stress and ferroptosis in cardiomyocytes via PI3K/AKT-mediated mitochondrial dysfunction. Moreover, GPX4 expression was decreased and ASCL4 level was higher following DOX treatment or the combination therapy of LAP and DOX.
Ropivacaine [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [4]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
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.

    Click to Show/Hide
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.
References
Ref 1 Curcumin Represses Colorectal Cancer Cell Proliferation by Triggering Ferroptosis via PI3K/Akt/mTOR Signaling. Nutr Cancer. 2023;75(2):726-733. doi: 10.1080/01635581.2022.2139398. Epub 2022 Nov 8.
Ref 2 Lapatinib induces mitochondrial dysfunction to enhance oxidative stress and ferroptosis in doxorubicin-induced cardiomyocytes via inhibition of PI3K/AKT signaling pathway. Bioengineered. 2022 Jan;13(1):48-60. doi: 10.1080/21655979.2021.2004980.
Ref 3 -Lipoic acid alleviates ferroptosis in the MPP(+) -induced PC12 cells via activating the PI3K/Akt/Nrf2 pathway. Cell Biol Int. 2021 Feb;45(2):422-431. doi: 10.1002/cbin.11505. Epub 2020 Dec 8.
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 FNDC5 Causes Resistance to Sorafenib by Activating the PI3K/Akt/Nrf2 Pathway in Hepatocellular Carcinoma Cells. Front Oncol. 2022 Mar 22;12:852095. doi: 10.3389/fonc.2022.852095. eCollection 2022.
Ref 6 Cellular protection using Flt3 and PI3K inhibitors demonstrates multiple mechanisms of oxidative glutamate toxicity. Nat Commun. 2014 Apr 17;5:3672. doi: 10.1038/ncomms4672.