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

Russel J. Reiter, Ramaswamy Sharma, Qiang Ma, Sergio Rosales-Corral, Walter Manucha

Research output: Contribution to journalArticlepeer-review

Abstract

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 healthy 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 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 is both produced and released in a circadian manner from the pineal gland and likely by the mitochondria of all normal cells in a non-circadian manner. In cancer cells, melatonin forces them to abandon aerobic glycolysis and function phenotypically as a normal cell by upregulating the enzyme, pyruvate dehydrogenase complex, that catalyzes pyruvate to acetyl-CoA; 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 reverts them to a normal cell phenotype thereby reducing the rapid cell proliferation and aggressive nature of cancer cells.

Original languageEnglish (US)
Pages (from-to)85-98
Number of pages14
JournalJournal of Current Science and Technology
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2020
Externally publishedYes

Keywords

  • Aerobic glycolysis
  • Angiogenesis
  • Cancer metastasis
  • Glucose metabolism
  • Hypoxia inducible factor-1α
  • Pyruvate dehydrogenase kinase

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Circadian and non-circadian melatonin: Influences on glucose metabolism in cancer cells'. Together they form a unique fingerprint.

Cite this