Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0385)
Name
Polyphyllin III
Drug Type
Small molecule
Full List of Ferroptosis Target Related to This Drug
Cystine/glutamate transporter (SLC7A11)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Regulator Krueppel-like factor 4 (KLF4) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Hs-578T cells Invasive breast carcinoma Homo sapiens CVCL_0332
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
HBL-100 cells Normal Homo sapiens CVCL_4362
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
In Vivo Model
MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 106 cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day.

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Response regulation Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis.
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Driver
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
Hs-578T cells Invasive breast carcinoma Homo sapiens CVCL_0332
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
T-47D cells Invasive breast carcinoma Homo sapiens CVCL_0553
HBL-100 cells Normal Homo sapiens CVCL_4362
BT-549 cells Invasive breast carcinoma Homo sapiens CVCL_1092
MDA-MB-453 cells Breast adenocarcinoma Homo sapiens CVCL_0418
In Vivo Model
MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 106 cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm3, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day.

    Click to Show/Hide
Response regulation Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis.
References
Ref 1 Polyphyllin -Induced Ferroptosis in MDA-MB-231 Triple-Negative Breast Cancer Cells can Be Protected Against by KLF4-Mediated Upregulation of xCT. Front Pharmacol. 2021 May 10;12:670224. doi: 10.3389/fphar.2021.670224. eCollection 2021.