期刊
CANCER LETTERS
卷 315, 期 2, 页码 112-121出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.07.032
关键词
Vorinostat; Apoptosis; Caspase-3; P38 MAPK; Breast cancer
类别
资金
- [20790940]
Vorinostat is a histone deacetylase inhibitor that effectively suppresses cancer-cell proliferation by inducing cell-cycle arrest and/or apoptosis. We now show the involvement of p38 mitogen-activated protein kinase (MAPK) in the regulation of vorinostat-induced apoptosis in MDA-MB-231 human breast cancer cells. Vorinostat induced the hyperacetylation of histone H3, which correlated to apoptosis induction. Vorinostat-induced apoptosis occurred in parallel with the phosphorylation of p38 MAPK and the dephosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Knockdown of p38 MAPK prominently abrogated apoptosis induction and was accompanied by decreased caspase-3 cleavage. These findings support the notion that the activation of the p38 MAPK pathway followed by caspase-3 cleavage is responsible for vorinostat-induced apoptosis in MDA-MB-231 cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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