Pro-oxidant effect of melatonin in tumour leucocytes: relation with its cytotoxic and pro-apoptotic effects

Melatonin has many effects on a wide range of physiological functions and is involved in a number of pathological events including oncostatic and neoplastic processes. The tissue protective actions of melatonin are attributed to its well-known antioxidant activity though melatonin might also exert pro-oxidant effects, particularly in tumour cells. This study evaluated the pro-oxidant effects of melatonin in tumour cell lines of human haematopoietic origin. Melatonin treatment is able to stimulate production of intracellular reactive oxygen species (ROS), as revealed by the increase in rhodamine-123 fluorescence, which was associated with significant cytotoxicity and activation of caspase activities. Furthermore, pre-treatment of cells with well-known antioxidants, such as N-acetyl-L-cysteine (NAC), trolox, PEG-catalase and reduced glutathione (GSH), reversed the effects of melatonin on both intracellular ROS production, as on the cytotoxicity and caspase activation. This pro-oxidant action of melatonin may assist in limiting tumour cell growth.