Melatonin provokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pathway activation.
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.
Trubiani
Oriana
O
Dipartimento di Scienze Odontostomatologiche, Università di Chieti-Pescara, Via dei Vestini, Chieti, Italy. trubiani@unich.it
Recchioni
Rina
R
Moroni
Fausto
F
Pizzicannella
Jacopo
J
Caputi
Sergio
S
Di Primio
Roberto
R
D017304:Annexin A5 / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000503:physiopathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045304:Cytochromes c / Q000096:biosynthesis; D015536:Down-Regulation; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D008550:Melatonin