Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Melatonin is a natural substance ubiquitously distributed and present in almost all living species, from unicellular organisms to humans. Melatonin is synthesized not only in the pineal gland but also in most tissues in the body where it may have a cytoprotective function via paracrine or autocrine effects. Melatonin is effective in suppressing neoplastic growth in a variety of tumors. The mechanisms involved include antiproliferative effects via modulation of cell cycle, ability to induce apoptosis in cancer cells, anti-angiogenic and antimetastatic effects, anti-estrogenic activity, the capacity to decrease telomerase activity, immune modulation, and direct and indirect antioxidant effects. Besides these oncostatic properties, melatonin deserves to be considered in the treatment of cancer for two other reasons. First, because its hypnotic-chronobiotic properties, melatonin use that can allow the clinician to effectively address sleep disturbances, a major co-morbidity in cancer. Second, because melatonin’s anxiolytic and antidepressant effects, it has a possible application in two other major co-morbidities seen in cancer patients, i.e. depression and anxiety. This report summarizes the possible mechanisms involved in melatonin oncostasis and reviews what is known about the clinical application of melatonin as an adjuvant therapy in cancer patients.