Melatonin cytotoxicity in human leukemia cells: relation with its pro‐oxidant effect

Abstract

Melatonin has a variety of functions in human physiology and is involved in a number of pathological events including neoplastic processes. The tissue protective actions of melatonin are attributed to its antioxidant activity though, under certain conditions, melatonin might also exert oxidant effects, particularly in cancer cells. This study evaluated the effects of 10(-5) and 10(-3) m concentrations of melatonin on human leukemia cells. Moderate cytotoxic effects of melatonin at 10(-3) m concentrations were observed in CMK, Jurkat and MOLT-4 cells which was associated with significant reactive oxygen species (ROS) generation. Melatonin treatment was not associated with significant cytotoxicity in HL-60 cells, although the generation of ROS was significantly increased. K562 and Daudi cells did not appear to be effected by melatonin treatment. Cellular membrane lipid peroxidation was not influenced by melatonin with the exception of CMK cells. Cell cycle kinetics were not affected in melatonin-treated samples, again with the exception of CMK cells which showed increased apoptosis. Melatonin, therefore, induces the production of ROS that may be associated with cytotoxicity depending on the concentration of melatonin in some leukemia cells and does not appear to stimulate leukemia cell growth. These pro-oxidant actions of melatonin may assist in limiting leukemic cell growth.

Melatonin decreases cell proliferation, impairs myogenic differentiation and triggers apoptotic cell death in rhabdomyosarcoma cell lines

“…Whereas in normal cells melatonin and its metabolites act as efficient radical scavengers (63), it has been suggested that changes in the oxidative status account for the ability of melatonin to induce apoptosis in cancer cells (62,64,65). In this regard, a correlation between the increase in ROS production and the induction of melatonin-driven apoptosis has been reported in several cell lines (66). Consistent with this evidence, we have preliminarily observed a reduction in the melatonin cytotoxic effect by pretreating RMS cells with vitamin E (data not shown), a lipid-soluble antioxidant molecule.…”

Melatonin and the aging brain

“…The evidence for a direct effect rests on the fact that melatonin can act as a powerful free radical scavenger in isolated cell-free systems (Beyer et al, 1998;Tan et al, 2002). Skaper et al (1999), Cheung (2003) There are however reports that melatonin can act in a prooxidant in such systems Buyukavci et al, 2006). Melatonin is present within brain at a concentration (around 4 pM) that is only 5% of that found in serum , and -unless it were to be highly concentrated in a localized area -can make little scavenging contribution in comparison to predominant antioxidant species such as glutathione (present in millimolar amounts) and a-tocopherol (5 mM, Sanchez-Moreno et al, 2004).…”

Promising Role of Melatonin as Neuroprotectant in Neurodegenerative Pathology

“…Protective effect of melatonin against cytotoxic effect of O 2 molecule has also been reported in cerebellar granular cells [50,51]. However, contradictory reports have showed that melatonin has some pro-oxidant capability [49,[52][53][54]. Studies in cell lines have showed that the pro-oxidant capacity of melatonin could be utilized in the treatment of cancer [54][55][56][57].…”