Melatonin reduces pancreatic tumor cell viability by altering mitochondrial physiology.
Melatonin reduces proliferation in many different cancer cell lines. Thus, melatonin is considered a promising antitumor agent, promoting apoptosis in tumor cells while preserving viability of normal cells. Herein, we examined the effects of melatonin on the pancreatic AR42J tumor cell line. We have analyzed cytosolic-free Ca(2+) concentration ([Ca(2+) ](c) ), mitochondrial-free Ca(2+) concentration ([Ca(2+) ](m) ), mitochondrial membrane potential (Ψm), mitochondrial flavin adenine dinucleotide (FAD) oxidative state, cellular viability and caspase-3 activity. Our results show that melatonin induced transient changes in [Ca(2+) ](c) and [Ca(2+) ](m) . Melatonin also induced depolarization of Ψm and led to a reduction in the level of oxidized FAD. In addition, melatonin reduced AR42J cell viability. Finally, we found a Ca(2+) -dependent caspase-3 activation in response to melatonin. Collectively, these data support the likelihood that melatonin reduces viability of tumor AR42J cells via its action on mitochondrial activity and caspase-3 activation.
Department of Physiology, Cell Physiology Research Group, University of Extremadura, Caceres, Spain. agmateos@unex.es
Antonio
A
Gonzalez
Angel
A
del Castillo-Vaquero
Alvaro
A
Miro-Moran
Jose A
JA
Tapia
Gines M
GM
Salido
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats
D053148:Caspase 3; D008550:Melatonin; D002118:Calcium