Melatonin in cell fate decisions: Mechanistic perspectives and therapeutical potential

Abstract

Melatonin, an indolamine derived from the amino-acid tryptophan via synthesis of serotonin, is secreted by the pineal gland in cyclical periods. In mammals, melatonin is involved in physiological processes, such as sleep/wake regulation in the circadian cycle. It has antioxidant oncostatic and anti-inflammatory properties, functions as an immunomodulator, and stimulates bone metabolism. In particular, the antitumor effects of melatonin, have been studied in multiple cancer cell types including melanoma, breast and prostate cancer, lymphoma, ovarian and colorectal cancer. This chapter summarizes the numerous observations about melatonin anticancer effects in both in vivo and in vitro studies published in recent years as well as the action mechanisms of melatonin involved in its anticarcinogenic activity focusing on the signalling pathways that regulate programmed cell death. In the majority of studies, melatonin has shown to inhibit development and/or growth of various experimental animal tumors and human cancer cell lines in vitro promoting apoptosis in contrast to the obvious inhibition of apoptotic processes in normal cells (focused in immune cells and neurons). Furthermore, if melatonin uniformly induced apoptosis in cancer cells, the findings could have important clinical utility given that many tumors show resistance to drug treatment due to their resistance to undergo apoptosis.