The Central Role Of Nadph Depletion In Mnte-2-Pyp-Induced Prostate Cancer Cell Growth Inhibition

•This study demonstrates that the combination of MnTE-2-PyP and radiation enhances energy demands which alters oxidative phosphorylation, glycolysis and glucose uptake in prostate cancer cells.•MnTE-2-PyP inhibits key enzymes in the pentose phosphate pathway, which results in reduced NADPH levels in prostate cancer cells.•Treatment with MnTE-2-PyP and radiation causes changes in the sphingomyelin/ceramide pathways as compared to irradiated alone prostate cancer cells.•We postulate that the increase in sphingomyelin synthesis is in response to lipid peroxidation observed in prostate cancer cells treated with MnTE-2-PyP and radiation to repair the damaged membranes.