Understanding the role of melatonin in cancer metabolism

Abstract

Oncogenes alters metabolic pathways while the resulted metabolites, in turn,
 modifies the expression and production of oncogenes or tumor suppressors. Metabolic
 reprogramming has been considered as a consequence of oncogenes’ activity more
 than a phenotypic change of cancer cells. Currently, three different metabolic
 alterations for cancer cells, i.e. an increased ability to acquire nutrients,
 preferred metabolic pathways or differentiation pathways, have been described.
 Melatonin is a molecule which has been extensively investigated since it was
 discovered more than 60 years ago. From the aggregation of melanophores to
 antioxidant chain reactions, melatonin has been proposed to be an important
 molecule affecting the physiology of mammals but also the biology of
 unicellular organisms. Thus, the decrease in melatonin synthesis in humans with
 age has been related to several diseases including neurodegeneration and
 cancer. For many years, it has been believed that melatonin crosses biological
 membranes easily to exert its functions. However, this notion has been
 challenged by recent discovery that majority of melatonin might cross biological
 membranes through glucose transporters. This initial observation has generated a
 new important idea about melatonin’s function, that is, the membrane transportation
 of melatonin and glucose by the same transporter in cancer cells would be a new
 promising mechanism of this indole by either reprogramming glucose metabolism,
 impeding nutrients uptake or assigning preferred metabolic pathways in cancer
 cells. In this review, we will focus the role of melatonin as an
 antiproliferative agent, and its connection with metabolic changes due to
 melatonin competition with glucose.