Melatonin as an Anti-Cancer Molecule: A Retrospective Perspective

Etymologically, melatonin (N-acetyl-5-methoxytryptamine) can be traced back to the origin of life. The first origin of melatonin was detected in cyano-bacteria. As considering the endosymbiont hypothesis, cyanobacteria were engulfed by the animal and plant cells. Later on, these bacteria performed the roles of mitochondria and chloroplastids in animals and plant cells respectively. Inner matrices of these organelles are having melatonin and probable function of this intraorganelle melatonin is to protect the organelles from the detrimental effects from free radicals (Reactive Oxygen Species; ROSs and Reactive Nitrogen Species; RNSs). In higher animals, melatonin is synthesized and secreted by the pineal gland mainly during the night, since light exposure suppresses its production. Other than pineal gland, melatonin is secreted from several different organs like retina, gastro-intestinal tract. The secretion of this hormone is regulated by several environmental factors like photo-period, temperature, humidity etc. Melatonin can exert its function either by as a free molecule or by its membrane bound receptors MT1 and MT2 respectively. Modulations of melatonin receptors results in stimulation of apoptosis, regulation of pro-survival signaling, inhibition on angiogenesis, metastasis, and induction of epigenetic alteration. Melatonin could also be utilized as adjuvant of cancer therapies, through reinforcing the therapeutic effects and reducing the side effects of chemotherapies or radiation. Melatonin could be an excellent candidate for prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer and colorectal cancer. This review summarized the anticancer efficacy of melatonin, based on the results of epidemiological, experimental and clinical studies.