CYP2E1 overexpression protects COS-7 cancer cells against ferroptosis.

Ferroptosis is a recently described form of regulated cell death initiated by the iron-mediated one-electron reduction of lipid hydroperoxides (LOOH). Cytochrome P450 2E1 (CYP2E1) induction, a consequence of genetic polymorphisms or/and gene induction by xenobiotics, may promote ferroptosis by contributing to the cellular pool of LOOH. However, CYP2E1 induction also increases the transcription of anti-ferroptotic genes that regulate the activity of glutathione peroxidase 4 (GPX4), the main ferroptosis inhibitor.