S‐Methyl Methanethiosulfonate, the Main Human Metabolite of S‐Methyl‐L‐Cysteine Sulfoxide, Alters Energy Metabolism in Prostate Cancer Cells

ABSTRACT Cruciferous and allium vegetables contain the sulfur compound S‐methyl‐L‐cysteine‐sulfoxide (SMCSO). Considering SMCSO is found at a higher abundance compared to the glucosinolates, there are limited reports on its effect on health, with the majority of the evidence on the beneficial effects on glucose metabolism in rodent models. In the current study, we investigated the metabolic effects of SMCSO and its metabolite, S‐methyl methanethiosulfonate (MMTSO), on prostate cancer metabolism. DU145 prostate cancer cells were cultured in 5.5 mM (basal), 10 mM (intermediate) and 25 mM (high) glucose concentrations in the presence of SMCSO or MMTSO (100 µM). Using Seahorse technology, MMTSO but not SMCSO reduced mitochondrial metabolism, mitochondrial ATP, and the percentage of oxidative phosphorylation and increased the fatty acid dependency of DU145 cells. Transcriptomic and metabolomic analyses observed cellular and energy metabolism pathways and immune response changes. These data show that MMTSO alters several features of energy metabolism in DU145 prostate cancer cells, shifting them towards a non‐cancerous phenotype. These data are consistent with the notion that MMTSO may contribute to the beneficial effects of a broccoli‐rich diet and metabolic effects of prostate cancer.