Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis.

Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis. Eur J Pharm Sci. 2020 Jul 01;:105450 Authors: Xu X, Zhang X, Wei C, Zheng D, Lu X, Yang Y, Luo A, Zhang K, Duan X, Wang Y Abstract Recent studies have revealed the critical roles of ferroptosis in different physiological and pathological processes, however, its effects on the progression of colorectal cancer stem cells (CSCs) are still unclear. Here, we found that colorectal CSCs exhibited a remarkably lower level of reactive oxygen species (ROS), a higher level of cysteine, glutathione and SLC7A11 compared to colorectal cancer cells. Knockout of SLC7A11 increased the ROS level and reduced the levels of cysteine and glutathione, subsequently attenuating the viability of colorectal CSCs. Erastin, an inhibitor of SLC7A11, was found to hold a remarkably stronger cytotoxic effect on colorectal CSCs via in vitro and in vivo experiments. Finally, it was found that Erastin attenuated the chemoresistance of colorectal CSCs. This work indicates that colorectal CSCs are more sensitive to ferroptosis, which could be targeted to attenuate colorectal cancer progression and chemoresistance. PMID: 32621966 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research