Cytotoxic and apoptotic effects of melatonin hormone on NB4 leukemic cells

Introduction: Given to the fact that the high toxicity and side effects of chemotherapeutic drugs have limited their clinical use, it is not surprising that novel therapeutic drugs with less toxicity and more efficacy have entered into the novel protocols. Relatively, Melatonin, a main product of pineal gland, not only plays a key role in the regulation of circadian rhythm, but also exerts anti-proliferative and apoptotic effects on a wide range of tumors. The aim of this study was to evaluate the anti-proliferative and apoptotic effects of melatonin in acute promyelocytic leukemia-derived cell line NB4. Materials and Methods: NB4 cells were exposed to the increasing concentrations of the melatonin drug (0.5, 1, and 2 mM). Subsequently, metabolic activity, induction of apoptosis, caspase-3 activity, ROS production and apoptosis-related target genes were investigated using MTT assay, Annexin-V/PI staining, caspase-3 activity kit, cellular ROS assay kit and RQ-PCR analysis, respectively. Results: Our data delineated that melatonin resulted in the reduction of metabolic activity of NB4 cells in a dose- and time-dependent manner (P<0.05). Furthermore, melatonin increased the percentage of apoptotic cells (P<0.05) probably through induction of caspase-3 activity, increment in the intracellular level of ROS and alteration in the expression level of Bcl-2, survivin and Bax. Conclusion: The results of this study clearly indicated the anti-leukemic effect of melatonin in NB4 cells and is a promising as a candidate drug in the treatment of APL.