坏死性下垂
程序性细胞死亡
未折叠蛋白反应
化学
细胞凋亡
癌细胞
细胞生物学
活性氧
活力测定
钙
生物化学
癌症研究
生物
癌症
有机化学
遗传学
作者
Hao Kuang,Xianjun Sun,Ying Li,Meng Tang,Yan Wei,Yingying Shi,Ruibin Li,Guohui Xiao,Jinlin Kang,Fen Wang,Peng Jin,Hui Xu,Fuxiang Zhou
出处
期刊:FEBS Journal
[Wiley]
日期:2023-04-16
卷期号:290 (14): 3664-3687
被引量:17
摘要
Ferroptosis, featuring an iron-dependent peroxidation of lipids, is a novel form of programmed cell death that may hold great potential in cancer therapy. Our study found that palmitic acid (PA) inhibited colon cancer cell viability in vitro and in vivo, in conjunction with an accumulation of reactive oxygen species and lipid peroxidation. The ferroptosis inhibitor Ferrostatin-1 but not Z-VAD-FMK (a pan-caspase inhibitor), Necrostatin-1 (a potent necroptosis inhibitor), or CQ (a potent inhibitor of autophagy), rescued the cell death phenotype induced by PA. Subsequently, we verified that PA induces ferroptotic cell death through excess iron as cell death was inhibited by iron chelator deferiprone (DFP), while it was exacerbated by a supplement of ferric ammonium citrate. Mechanistically, PA affects intracellular iron content by inducing endoplasmic reticulum (ER) stress leading to ER calcium release and regulating transferrin (TF) transport through increasing cytosolic calcium levels. Furthermore, we observed that cells with high expression of CD36 were more vulnerable to PA-induced ferroptosis. Altogether, our findings reveal that PA engages in anti-cancer properties by activating ER stress/ER calcium release/TF-dependent ferroptosis, and PA might serve as a compound to activate ferroptosis in colon cancer cells with high CD36 expression.
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