Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis

摘要: Melatonin has the ability to intervene in initiation, progression and metastasis of some experimental cancers. A large variety potential mechanisms have been advanced describe metabolic molecular events associated with melatonin’s interactions cancer cells. There is one perturbation that common a number solid tumors accounts for cells actively proliferate, avoid apoptosis, readily metastasize, i.e., they use cytosolic aerobic glycolysis (the Warburg effect) rapidly generate necessary ATP required high demands are several drugs, referred as glycolytic agents, cause abandon shift more conventional mitochondrial oxidative phosphorylation synthesis normal In doing so, agents also inhibit growth. Herein, we hypothesize melatonin functions an inhibitor using mechanisms, downregulation enzyme (pyruvate dehydrogenase kinase) interferes conversion pyruvate acetyl CoA mitochondria, do other drugs. halts proliferative activity cells, reduces their metastatic causes them undergo apoptosis. This hypothesis discussed relation previously published reports. Whereas synthesized mitochondria this synthetic capability not present cell because depressed CoA; rate limiting synthesis, arylalkylamine-N-acetyltransferase. Finally, switch glucose oxidation from cytosol explains how become resistant chemotherapies re-sensitized same treatment when applied.