Requirement of p38 MAPK for a cell-death pathway triggered by vorinostat in MDA-MB-231 human breast cancer cells

Norihisa Uehara, Sayaka Kanematsu, Hisanori Miki, Katsuhiko Yoshizawa, Airo Tsubura

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)112-121
Number of pages10
JournalCancer Letters
Volume315
Issue number2
DOIs
Publication statusPublished - Feb 28 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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