Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade.

ABSTRACT: Dietary methionine interventions are beneficial to apoptosis-inducing chemotherapy and radiotherapy for cancer, while their effects on ferroptosis-targeting therapy and immunotherapy are unknown. Here we show the length of time methionine deprivation affects tumoral ferroptosis differently. Prolonged methionine deprivation prevents glutathione (GSH) depletion from exceeding the death threshold by blocking cation transport regulator homolog 1 (CHAC1) protein synthesis. Whereas, short-term methionine starvation accelerates ferroptosis by stimulating CHAC1 transcription. In vivo, dietary methionine with intermittent but not sustained deprivation augments tumoral ferroptosis. Intermittent methionine deprivation also sensitizes tumor cells against CD8⁺ T cell-mediated cytotoxicity an

SUBMITTER: Xue Y 

PROVIDER: S-EPMC10409767 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature