Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis

作者：Fang Zheng, Yeshu Wang, Qunfang Zhang, Qiuyuan Chen, Chun-Ling Liang, Huazhen Liu, Feifei Qiu, Yuchao Chen, Haiding Huang, Weihui Lu, Zhenhua Dai · 发表于：Frontiers in Pharmacology · 年份：2023 · DOI：10.3389/fphar.2023.1145407 · 被引用次数：44 · 研究领域：Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research、Cancer, Lipids, and Metabolism

Background: Ferroptosis is a new form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides and membrane damages. Recent studies have identified an important role for cancer cell ferroptosis in antitumor therapy. On the other hand, polyphyllin I (PPI) has been reported to exert antitumor effects on some types of cancers. However, it remains unknown whether or not PPI regulates cancer cell ferroptosis. Methods: Two types of human gastric cancer cells (AGS and MKN-45) were used to establish tumor xenograft models in nude mice that were treated with polyphyllin I (PPI) to observe tumor growth, while cells also were cultured for in vitro studies. Ferroptosis, based on the intracellular ROS/lipid ROS production and accumulation of ferrous ions, was detected using a fluorescence microscope and flow cytometer, while the expression of NRF2/FTH1 was measured using Western blotting assays. Results: Here we found that PPI inhibited the gastric cancer growth in vivo and in vitro while increasing the intracellular reactive oxygen species (ROS)/lipid peroxides and ferrous ions in the gastric cancer cells. PPI also decreased the levels of nuclear factor erythroid 2-related factor 2 (NRF2) and ferritin heavy chain 1 (FTH1) in gastric cancer cells in vitro . Moreover, liproxstain-1, an inhibitor of cell ferroptosis, mostly reversed the cell ferroptosis and tumor growth arrest induced by PPI. Finally, the effects of PPI on cancer cell ferroptosis were dimi...