Histone Deacetylases and their Inhibitors as Potential Therapeutic Drugs for cholangiocarcinoma - Cell Line findings

Ruethairat Sriraksa, Temduang Limpaiboon
2013 Asian Pacific Journal of Cancer Prevention  
Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213,
more » ... ll lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as determined by sulforhodamine assay. IC 50 and IC 20 were then analyzed for each agent and cell line. Moreover, 20 ) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic alternative therapeutic strategy in effective treatment of CCA.
doi:10.7314/apjcp.2013.14.4.2503 fatcat:6penqslinzcbxjan63eieyd3mm