Melanogenesis is a key parameter of differentiation in melanocytes and melanoma cells; therefore, searches for factors regulating this pathway are strongly desired. Herein, we investigated the effects of melatonin, a ubiquitous physiological mediator that is found throughout animals and plants. In mammals, the pineal gland secretes this indoleamine into the blood circulation to exert an extensive repertoire of biological activities. In vitro assessment indicated that melatonin arrests cell viability in highly pigmented MNT-1 melanoma cells, amelanotic Sk-Mel-28 melanoma as well as normal human melanocytes. Moreover, electron paramagnetic resonance (EPR) spectroscopy demonstrated that melatonin reduced melanin content. Alterations of melanogenesis by selected inhibitors, i.e., N-phynelthiourea or kojic acid were, interestingly, antagonized by melatonin while exogenously applied L-DOPA enhanced melanin synthesis as well as tyrosinase activity. Additionally, analysis using transmission electron microscopy showed that melatonin, particularly at higher dose of 10–3 M, triggered the appearance of premelanosomes (stage I-II of melanosome) and cells synthesize de novo endogenous melatonin (LC-MS). In conclusion, these studies show a regulatory capacity of melatonin in melanogenesis suggesting it could be an agent useful for treatment of pigmentary disorders.

Melatonin regulates melanin synthesis in human melanogenic cells