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Dichloroacetate attenuates the stemness of colorectal cancer cells via trigerring ferroptosis through sequestering iron in lysosomes
Author(s) -
Sun Jie,
Cheng Xiuqin,
Pan Shubo,
Wang Liangjing,
Dou Wenhuan,
Liu Jie,
Shi Xiaohua
Publication year - 2021
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.23057
Subject(s) - colorectal cancer , cancer research , cancer stem cell , downregulation and upregulation , stem cell , cell , mouse model of colorectal and intestinal cancer , chemistry , cancer , cancer cell , viability assay , programmed cell death , cell growth , medicine , biology , microbiology and biotechnology , biochemistry , apoptosis , gene
Colorectal cancer stem cell (CSC) has been regarded to be the root of colorectal cancer progression. However, there is still no effective therapeutic method targeting colorectal CSC in clinical application. Here, we investigated the effects of dichloroacetate (DCA) on colorectal cancer cell stemness. We showed that DCA could reduce colorectal cancer cell stemness in a dose‐dependent manner, which is evident by the decreased expression of stemness markers, tumor cell sphere‐formation and cell migration ability. In addition, it was found that DCA trigerred the ferroptosis of colorectal CSC, which is characterized as the upregulation of iron concentration, lipid peroxides, and glutathione level, and decreased cell viability. Mechanistic studies demonstrated that DCA could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA‐mediated attenuation on colorectal cancer cell stemness. Taken together, this work suggests that DCA might be a colorectal CSC‐killer.