Melatonin provokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pathway activation
Article first published online: 10 AUG 2005
Journal of Pineal Research
Volume 39, Issue 4, pages 425–431, November 2005
How to Cite
Trubiani, O., Recchioni, R., Moroni, F., Pizzicannella, J., Caputi, S. and Di Primio, R. (2005), Melatonin provokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pathway activation. Journal of Pineal Research, 39: 425–431. doi: 10.1111/j.1600-079X.2005.00270.x
- Issue published online: 10 AUG 2005
- Article first published online: 10 AUG 2005
- Received March 1, 2005; accepted June 24, 2005.
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Abstract: Apoptosis is an important cell suicide programme involved in physiological and pathological processes. Apoptosis can be induced in different ways depending on cell type and acquired signal. Melatonin, the major secretory product of the pineal gland, participates in many important physiological functions and displays a remarkable functional versatility exhibiting antioxidant, oncostatic, anti-aging, and immunomodulatory properties. Recently, it has been shown that, in addition to pineal gland, human lymphoid cells are an important physiological source of melatonin and that may be involved in the regulation of the immune system. In this work, we examine the effect of melatonin on RAMOS-1 human leukaemic cells. Cell growth and viability, DNA fragmentation and JC-1, and annexin V expression have been determined. To elucidate the mechanism of action of melatonin, Western blot analyses for Bcl-2 and caspase-3 expression, and cytochrome c release were carried out. The results suggest that the apoptotic effect of melatonin is associated with cell-cycle arrest, downregulation of Bcl-2, mitochondrial membrane depolarization, cytochrome c release and activation of caspase-3. The intrinsic (mitochondrial dependent) pathway of caspase activation is the ‘point of no return’ commitment to cell death. Taken together, our study indicates that melatonin may play a role as potential therapeutic drug in specific lymphoproliferative diseases.