Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines.

ABSTRACT: Sorafenib, a protein kinase inhibitor approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma, has been repeatedly reported to induce ferroptosis by possibly involving inhibition of the cystine/glutamate antiporter, known as system x_c^-. Using a combination of well-defined genetically engineered tumor cell lines and canonical small molecule ferroptosis inhibitors, we now provide unequivocal evidence that sorafenib does not induce ferroptosis in a series of tumor cell lines unlike the cognate system x_c^- inhibitors sulfasalazine and erastin. We further show that only a subset of tumor cells dies by ferroptosis upon sulfasalazine and erastin treatment, implying that certain cell lines appear to be resistant to system

SUBMITTER: Zheng J 

PROVIDER: S-EPMC8277867 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature