The Potential Oncostatic Effects of Melatonin against Prostate Cancer

Melatonin is an endogenous indolamine, synthesized and secreted from the pineal gland. The environmental light-dark cycle is the primary regulator of melatonin synthesis. Darkness during the subjective night induces noradrenaline secretion, which stimulates pinealocytes for melatonin production. Melatonin exhibits anticancer effects and different physiological functions through the membrane-bound G-protein-coupled MT1 and MT2 receptors. Impaired circadian activity, indoor or outdoor light pollution, shift work, night work, and jet lag suppress normal melatonin synthesis. Decreased melatonin concentration causes impaired anticancer effects that adversely affect the progression of different cancers, including prostate. Melatonin differentially regulates the cell cycle, cell survival, and metabolism in malignant cells in contrast to normal prostate epithelial cells. Melatonin promotes the nuclear exclusion of androgen receptors without suppressing the expression of this receptor. This indirect effect blocks the androgenic response in prostate cancer cells. It acts as a cytostatic and cytotoxic agent, prevents cell proliferation, and activates an apoptotic response. Melatonin also inhibits HIF-1α activity and the expression of vascular endothelial growth factors to suppress angiogenesis. This indolamine restricts alteration of metabolic activity, invasion, and metastasis. Melatonin has therapeutic importance. It decreases the side effects of anticancer treatment and mitigates adverse effects after prostatectomy and radiotherapy. Melatonin blocks the recurrence of prostate cancer as well as hormone-refractory effects during androgen deprivation therapy. The present review discusses the multifaceted effects of melatonin against prostate cancer.