期刊
CANCER SCIENCE
卷 108, 期 11, 页码 2187-2194出版社
WILEY
DOI: 10.1111/cas.13380
关键词
Cell death; glutathione peroxidase; iron; Ras; reactive oxygen species
类别
资金
- Institute for Molecular and Cellular Regulation, Gunma University [16034, 16035]
- Gunma University Medical Innovation project
- Grants-in-Aid for Scientific Research [17J40226, 17K08528] Funding Source: KAKEN
In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOX) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA-mediated silencing of ALOX15 significantly decreased both erastin-induced and RSL3-induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds. Immunofluorescence analyses revealed that the ALOX15 protein consistently localizes to cell membrane during the course of ferroptosis. Importantly, treatments of cells with ALOX15-activating compounds accelerated cell death at low, but not high doses of erastin and RSL3. These observations suggest that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据