In cancer cells, glucose is primarily metabolized to pyruvate and then to lactate in the cytosol. By allowing the conversion of pyruvate to acetyl-CoA in mitochondria, melatonin reprograms glucose metabolism in cancer cells to a normal cell phenotype. Acetyl-CoA in the mitochondria also serves as a necessary co-factor for the rate-limiting enzyme in melatonin synthesis, thus ensuring melatonin production in mitochondria of normal cells.
Keywords: Warburg effect; free radicals; lactate metabolism; oxidative phosphorylation; oxidative stress; pyruvate dehydrogenase complex; pyruvate dehydrogenase kinase; reactive oxygen species.