Circadian and non-circadian melatonin: Influence on glucose metabolism in cancer cells

• Autores: Reiter, Russel; Sharma, Ramaswamy; Ma, Qiang; Rosales Corral, Sergio; Manucha, Walter Ariel Fernando
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: AEROBIC GLYCOLYSIS; ANGIOGENESIS; CANCER METASTASIS; GLUCOSE METABOLISM; HYPOXIA INDUCIBLE FACTOR-1Α; PYRUVATE DEHYDROGENASE KINASE
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

This review considers the role of melatonin as an oncostatic agent and particularly as to how it relates to the mechanisms by which melatonin regulates glucose metabolism in cancer cells. Many tumor cells adopt a means of glucose utilization that is different from that of normal cells. Thus, these cancer cells rapidly take up and metabolize glucose and after it is converted to pyruvate, they accelerate the production of lactate which is abundantly released into the circulation. The change in metabolism that cancer cells makes is referred to as the Warburg effect, or aerobic glycolysis. The switch to aerobic glycolysis affords cancer cells major advantages in terms of an accelerated rate of ATP production and the synthesis of abundant molecular building blocks required for rapid proliferation, invasion, and metastasis. In normal cells, the bulk of the pyruvate formed is shunted into the mitochondria for conversion to acetyl-CoA. Melatonin forces cancer cells to abandon aerobic glycolysis and function with a normal cell phenotype. The oncostatic agent, melatonin, does this by upregulating the enzyme, pyruvate dehydrogenase complex, that ensures pyruvate to acetyl-CoA metabolism; this is presumably achieved by the direct or indirect inhibition of pyruvate dehydrogenase kinase, which normally downregulates pyruvate dehydrogenase complex. By depriving cancer cells of aerobic glycolysis, melatonin converts them to a normal cell phenotype which reduces the rapid cell proliferation and aggressive nature of cancer cells.
Fil: Reiter, Russel. University Of Lodz; Argentina
Fil: Sharma, Ramaswamy. No especifíca;
Fil: Ma, Qiang. No especifíca;
Fil: Rosales Corral, Sergio. Instituto Mexicano del Seguro Social; México
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina