Phillyrin sensitizes lung cancer cells to ferroptosis through inhibiting FTH1/SLC7A11 axis

作者：Xu Tang, Jiajia Teng, Keyin Lu · 发表于：International Journal of Clinical Pharmacology and Therapeutics · 年份：2023 · DOI：10.5414/cp204475 · 被引用次数：10 · 研究领域：Ferroptosis and cancer prognosis、Cancer, Lipids, and Metabolism、Trace Elements in Health

, has been explored as a potential anticancer agent in some cancer types. However, it is unclear whether and how PHN could promote the death of non-small cell lung cancer (NSCLC) cells by inducing ferroptosis. Our study showed for the first time that PHN induced cell death and attenuated cell proliferation in NSCLC cells in vitro and in vivo. Functional assays showed that ferroptosis was the predominant form that contributed to PHN-induced cell death of NSCLC cells. Mechanistically, NSCLC cells exposed to PHN had a decreased ferritin heavy chain 1 (FTH1) and SLC7A11 protein expression. Exogenetic overexpression of FTH1 substantially abrogated the tumor-inhibiting effects of PHN and further upregulated the expression of SLC7A11 in NSCLC cells. In conclusion, our findings suggest that the natural product PHN exerted its antitumor activity in NSCLC by promoting ferroptosis, and the FTH1/SLC7A11 axis plays an indispensable role in PHN-induced ferroptotic cell death.