An Overview of the Neuroendocrine Regulation of Experimental Tumor Growth by Melatonin and Its Analogues and the Therapeutic Use of Melatonin in Oncology

Scientific support for melatonin as a physiological, neuroendocrine regulator of a wide spectrum of carcinogenic processes and as a therapeutic anticancer agent in experimental and clinical settings continues to increase. In the experimental setting, melatonin and some of its analogues have efficacy in inhibiting the growth of a wide variety of solid neoplasms, particularly those related to hormone-responsive tumors. This is due primarily to a cytostatic action of melatonin although, under certain experimental conditions, melatonin may have cytotoxic effects as well. Based on its chronobiologic properties, melatonin is most efficacious in vivo when administered near the end of the light phase prior to the rise in endogenous melatonin secreted by the pineal gland Numerous in vitro studies and some in vivo investigations have provided valuable insights into the potential mechanisms underlying melatonin’s action as an oncostatic hormone. These mechanisms include melatonin modulation of hormone receptor expression and regulation, signal transduction events, transcriptional control, genomic interactions, redox processes, and metabolic activities. Melatonin has also been tested in a number of clinical trials for its therapeutic efficacy as either a single agent or, more commonly, in combination with established chemo- or radiotherapeutic approaches.