Sensitization of cancer cells to ferroptosis coincident with cell cycle arrest.

ABSTRACT: Ferroptosis is a non-apoptotic form of cell death that can be triggered by inhibiting the system x_c^- cystine/glutamate antiporter or the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). We have investigated how cell cycle arrest caused by stabilization of p53 or inhibition of cyclin-dependent kinase 4/6 (CDK4/6) impacts ferroptosis sensitivity. Here, we show that cell cycle arrest can enhance sensitivity to ferroptosis induced by covalent GPX4 inhibitors (GPX4i) but not system x_c^- inhibitors. Greater sensitivity to GPX4i is associated with increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids (PUFA-PLs). Higher PUFA-PL abundance upon cell cycle arrest involves reduced expression of membrane-bound O-acyltr

SUBMITTER: Rodencal J 

PROVIDER: S-EPMC10925838 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature