biostudies-literatureSwamynathan MMNCI NIH HHSeadk9167https://www.ebi.ac.uk/biostudies/studies/S-EPMC11975464biostudies-literatureUnknown386(6720)Men taking antioxidant vitamin E supplements have increased prostate cancer (PC) risk. However, whether pro-oxidants protect from PC remained unclear. In this work, we show that a pro-oxidant vitamin K precursor [menadione sodium bisulfite (MSB)] suppresses PC progression in mice, killing cells through an oxidative cell death: MSB antagonizes the essential class III phosphatidylinositol (PI) 3-kinase VPS34-the regulator of endosome identity and sorting-through oxidation of key cysteines, pointing to a redox checkpoint in sorting. Testing MSB in a myotubular myopathy model that is driven by loss of <i>MTM1</i>-the phosphatase antagonist of VPS34-we show that dietary MSB improved muscle histology and function and extended life span. These findings enhance our understanding of pro-oxidant selScience (New York, N.Y.)Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.PMC11975464R01 CA193256P30 CA045508R01 CA275128R01 CA188134R01 CA190092U01 CA210240R01 CA229699R01 CA137050U01 CA224013Liu JMinicozzi FSpokaite SChakrabarty RPHicks JBChandel NSSwamynathan MMKim STEgeblad MWilkinson JEGineste CNowak DGZhao XRivera KTuveson DATrotman LCMathew GPark YDiermeier SDCifani PAlmeida ASDessus ANAlsudani HCheng EGhosh DChang KKendall JReczek CRKuang SGong GQJanowitz TWigler MReiss DGimotty PAWatrud KECox HWee TLHerzka TWilliams RLDoherty MRPappin DJKlingbeil OVakoc CRLaporte JLocasale JWfalseDietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.Men taking antioxidant vitamin E supplements have increased prostate cancer (PC) risk. However, whether pro-oxidants protect from PC remained unclear. In this work, we show that a pro-oxidant vitamin K precursor [menadione sodium bisulfite (MSB)] suppresses PC progression in mice, killing cells through an oxidative cell death: MSB antagonizes the essential class III phosphatidylinositol (PI) 3-kinase VPS34-the regulator of endosome identity and sorting-through oxidation of key cysteines, pointing to a redox checkpoint in sorting. Testing MSB in a myotubular myopathy model that is driven by loss of <i>MTM1</i>-the phosphatase antagonist of VPS34-we show that dietary MSB improved muscle histology and function and extended life span. These findings enhance our understanding of pro-oxidant sel2024-01-01T00:00:00Z2024 Oct2026-06-02T04:17:38.136Z2025-07-05T03:04:47.268ZS-EPMC119754643944694810.1126/science.adk9167