論文 - 詳細
| RRC ID | 66998 |
|---|---|
| 著者 | Zheng J, Sato M, Mishima E, Sato H, Proneth B, Conrad M. |
| タイトル | Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines. |
| ジャーナル | Cell Death Dis |
| 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 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 bona fide 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-. |
| 巻・号 | 12(7) |
| ページ | 698 |
| 公開日 | 2021-7-13 |
| DOI | 10.1038/s41419-021-03998-w |
| PII | 10.1038/s41419-021-03998-w |
| PMID | 34257282 |
| PMC | PMC8277867 |
| MeSH | Amino Acid Transport System y+ / antagonists & inhibitors Amino Acid Transport System y+ / genetics Amino Acid Transport System y+ / metabolism Animals Antineoplastic Agents / pharmacology* Cell Line, Tumor Drug Resistance, Neoplasm Ferroptosis / drug effects* HEK293 Cells Humans Mice Neoplasms / drug therapy* Neoplasms / genetics Neoplasms / metabolism Neoplasms / pathology Piperazines / pharmacology Protein Kinase Inhibitors / pharmacology* Sorafenib / pharmacology* Sulfasalazine / pharmacology |
| IF | 6.304 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16F10(RCB2630) |