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Melatonin enhances hydrogen peroxide-induced apoptosis in human promyelocytic leukaemia HL-60 cells

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Abstract

Melatonin is an indoleamine secreted by the pineal gland that shows multiple tasks. This ubiquitously acting free radical scavenger has recently been shown to stimulate the production of reactive oxygen species (ROS) in tumour cells, making them undergo apoptosis, whilst it prevents apoptosis in healthy cells. The mechanisms by which melatonin exerts these dual actions are, however, not yet clearly understood. Thus, the aim of this study was to further investigate how melatonin can enhance oxidative stress-induced apoptosis in a leukaemia cell line. The results show that melatonin increased the apoptotic effects of H2O2 in human myeloid HL-60 cells as assessed by cellular viability, mitochondrial permeability transition induction, mitochondrial membrane depolarization, ROS generation, caspases 3, 8 and 9 activity, phosphatidylserine externalization, and DNA fragmentation techniques. When healthy leucocytes were exposed to H2O2, melatonin increased the viability of the cells. Taken together, the findings indicate that melatonin is a potential physiological tool capable of protecting healthy cells from chemotherapy-induced ROS production as well as inducing tumour cell death. Because cancer cells manifest increased oxidative stress as a result of their elevated metabolism, the use of melatonin may be useful in impairing their ROS buffering capacity.

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Acknowledgments

This study was supported by the Junta de Extremadura (PRI07-A024) and the Ministerio de Ciencia e Innovación-Fondo Europeo de Desarrollo Regional grants (BFU2007-60091 and BFU2010-15049). I. Bejarano and S.D. Paredes are the beneficiaries of grants from the Consejería de Economía, Comercio e Innovación-Fondo Social Europeo (Junta de Extremadura, PRE06070 and REI09009, respectively). J. Espino is a beneficiary of a grant from the Ministerio de Ciencia e Innovación (AP2009-0753).

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Authors and Affiliations

  1. Department of Physiology, Faculty of Science, Neuroimmunophysiology and Chrononutrition Research Group, University of Extremadura, Avda. de Elvas, s/n, 06006, Badajoz, Spain

    Ignacio Bejarano, Javier Espino, Ana M. Marchena, Carmen Barriga, Sergio D. Paredes, Ana B. Rodríguez & José A. Pariente

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  1. Ignacio Bejarano
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  2. Javier Espino
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  3. Ana M. Marchena
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  4. Carmen Barriga
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  6. Ana B. Rodríguez
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  7. José A. Pariente
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Correspondence to Ignacio Bejarano.

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Bejarano, I., Espino, J., Marchena, A.M. et al. Melatonin enhances hydrogen peroxide-induced apoptosis in human promyelocytic leukaemia HL-60 cells. Mol Cell Biochem 353, 167–176 (2011). https://doi.org/10.1007/s11010-011-0783-8

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