2021年7月
Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines
Cell Death & Disease
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- 巻
- 12
- 号
- 7
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41419-021-03998-w
- 出版者・発行元
- Springer Science and Business Media LLC
<title>Abstract</title>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 xc−. 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 xc− 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 xc− inhibition, while others undergo ferroptosis-independent cell death. From these findings, we conclude that sorafenib does not qualify as a <italic>bona fide</italic> ferroptosis inducer and that ferroptosis induced by system xc− inhibitors can only be achieved in a fraction of tumor cell lines despite robust expression of SLC7A11, the substrate-specific subunit of system xc−.
- リンク情報
- ID情報
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- DOI : 10.1038/s41419-021-03998-w
- eISSN : 2041-4889