期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 218, 期 3, 页码 265-273出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2006.11.012
关键词
apoptosis; caspase-3; osteosarcoma cells; paroxetine; MAPKs; SSRIs
Selective scrotonin reuptake inhibitors (SSRIs), a group of antidepressants, are generally used for treatment of various mood and anxiety disorders. There has been much research showing the anti-tumor and cytotoxic activities of some antidepressants; but the detailed mechanisms were unclear. In Cultured human osteosarcoma cells (MG63), paroxetine reduced cell viability in a concentration- and time-dependent manner. Paroxetine caused apoptosis as assessed by propidium iodide-stained cells and increased caspase-3 activation. Although immunoblotting data revealed that paroxetine could activate the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terrninal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Paroxetine also induced [Ca2+](i) increases which involved the mobilization of intracellular Ca2+ stored in the endoplasmic reticulum and Ca2+ influx from extracellular medium, However, pretreatment with BAPTA/AM, a Ca2+ chelator, to prevent paroxetine-induced [Ca2+](i) increases did not protect 2 cells from death. The results suggest that in MG63 cells, paroxetine caused Ca2+-independent apoptosis via inducing p38 MAPK-associated caspase-3 activation. (c) 2006 Published by Elsevier Inc.
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