Ginsenoside (20)S-APPT induces ferroptosis in hepatocellular carcinoma and cholangiocarcinoma by targeting FSP1
文献类型：期刊论文
| 作者 | Liu, Fan-yu7,8; Yang, Yuan-jie7,8; Wang, Xue-long6; Hong, Yan8; Ou-Yang, Xiao-peng5,8; Chang, Lu4; Zhu, Nan-lin4; Huang, Ao3; Zhang, Min-min8 ; Liu, Jia2,4
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2025-06-23 |
| 页码 | 18 |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-025-01589-5 |
| 英文摘要 | Triggering ferroptosis has recently been recognized as a promising approach for cancer treatment. However, current ferroptosis inducers, such as glutathione peroxidase 4 (GPX4) inhibitors, face limitations in terms of druggability and safety. In this study, we performed a phenotypic screen of a 180-compound natural product library and identified (20S)-protopanaxatriol ((20)S-APPT), a ginsenoside derivative, as a potent ferroptosis inducer with a favorable safety profile both in vitro and in vivo. We demonstrated that (20)S-APPT induced ferroptosis by targeting the plasma membrane-localized CoQ10 oxidoreductase FSP1. FSP1 inhibition promoted ACSL4-dependent arachidonic acid oxidation and mitochondrial ROS production, thereby increasing ferroptosis. Intriguingly, we revealed that FSP1 inhibition alone was sufficient to trigger ferroptosis in a subset of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) cells. Furthermore, the combined inhibition of FSP1 and gamma-glutamylcysteine synthetase (GCS) synergistically induced ferroptosis in otherwise resistant cancer cells while sparing noncancerous cells. These results establish a previously unrecognized role for FSP1 in driving ferroptosis and highlight the therapeutic potential of cotargeting FSP1 and GCS in HCC and CCA. |
| WOS关键词 | SMALL-MOLECULE ; CELL-DEATH ; ACSL4 |
| 资助项目 | National Natural Science Foundation of China[82173831] ; Natural Science Foundation of China for Innovation Research Group[81821005] ; Shanghai Municipal Science and Technology Major Project ; Foundation of Shanghai Science and Technology Committee[21DZ2291100] ; Shandong Laboratory Program[SYS202205] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050102] ; Key R&D Program of Shandong Province[2024CXPT029] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001513729700001 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318618]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Jia; Geng, Mei-yu; Shen, Ai-jun |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310058, Peoples R China 3.Fudan Univ, Dept Liver Surg & Transplantat, Liver Canc Inst,Zhongshan Hosp, Key Lab Carcinogenesis & Canc Invas,Minist Educ, Shanghai 200032, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Belt & Rd Joint Lab Nat Prod & Drug Discovery, Shanghai 201203, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Lingang Lab, Shanghai 200031, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 8.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Fan-yu,Yang, Yuan-jie,Wang, Xue-long,et al. Ginsenoside (20)S-APPT induces ferroptosis in hepatocellular carcinoma and cholangiocarcinoma by targeting FSP1[J]. ACTA PHARMACOLOGICA SINICA,2025:18. |
| APA | Liu, Fan-yu.,Yang, Yuan-jie.,Wang, Xue-long.,Hong, Yan.,Ou-Yang, Xiao-peng.,...&Shen, Ai-jun.(2025).Ginsenoside (20)S-APPT induces ferroptosis in hepatocellular carcinoma and cholangiocarcinoma by targeting FSP1.ACTA PHARMACOLOGICA SINICA,18. |
| MLA | Liu, Fan-yu,et al."Ginsenoside (20)S-APPT induces ferroptosis in hepatocellular carcinoma and cholangiocarcinoma by targeting FSP1".ACTA PHARMACOLOGICA SINICA (2025):18. |
入库方式： OAI收割
来源：上海药物研究所
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