Melatonin, an indolamine derived from the amino-acid tryptophan, participates in diverse physiological functions and has
great functional versatility related to the regulation of circadian rhythms and seasonal behaviour, sexual development, retinal physiology,
tumour inhibition, as an antioxidant, immunomodulatory and anti-aging properties. In relation to its oncostatic properties, there is
evidence that tumor initiation, promotion or progression may be restrained by the night-time physiological surge of melatonin in the
blood or extracellular fluid. In addition, depressed nocturnal melatonin concentrations or nocturnal excretion of the main melatonin
metabolite, 6-sulfatoxymelatonin, were found in individuals with various tumor types. In the majority of studies, melatonin was shown to
inhibit development and/or growth of various experimental animal tumors and some human cell lines in vitro. Many tumors do not
respond to drug treatment due to their resistance to undergo apoptosis thereby contributing to the development of cancer. Thus, given the
importance of the apoptotic program in cancer treatment, the role of melatonin in influencing apoptosis in tumor cells attracted attention
because it seems that it actually promotes apoptosis in most tumor cells, in contrast to the obvious inhibition of apoptotic processes in
normal cells. Thus, this paper is also intended to provide to the reader an up-date of all the researches that have been carried out to date,
which investigate the proapoptotic effects of melatonin in experimental preclinical models of cancer (in vitro and in vivo) and the
underlying proposed action mechanism of this effects. If melatonin uniformly induces apoptosis in cancer cells, the findings could have
important clinical implications to improve the quality of live while preventing the appearance of cancer.
Keywords: Apoptosis, cancer cells, cancer therapy, caspase activation, cell cycle, cell death, extrinsic apoptotic pathway, intrinsic apoptotic pathway, melatonin, tumor.
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