Abstract 5376: Expression of histone deacetylases (HDACs) 1, 2, 3 and 7 in pancreatic cancer cell lines: The role of indole-3-carbinol.

Abstract

Abstract Pancreatic cancer has the poorest prognosis of most cancers, mainly due to its resistant phenotype. Early or late biomarkers are greatly needed in this cancer. Scientists have shown that epigenetic mechanisms may be involved in the etiology and progression of pancreatic cancer. Epigenetic changes involve modification of the DNA through hyper- and hypo-methylation, histone modification and modulation in expression of microRNAs. Histone deacetylases modify tails on the histones, which can result in repressive chromatin formation and inactivation of specific genes. This study, using real-time PCR, examined the level of HDACs 1, 2, 3 and 7 in four pancreatic cancer cell lines (BXPC, CFPAC,ASPC and MIA). The highest level of expression of HDAC 1 and 3 was found in CFPAC and MIA cells compared to BXPC and ASPC cells. Indole-3 carbinol, in previously published studies from our laboratory, have shown several anti-cancer activities, including the re-expression of p16 in MIA cells (Lyn-Cook et al, 2010 Anticancer Res., 30:4907-4914). The current study demonstrated that indole-3-carbinol at concentrations of 20 μM and 100 μM significantly decreased expression of HDAC 3 by 2-fold and 3-fold in MIA cells, respectively. Results further showed that indole-3 carbinol decreased expression of HDAC 1 in CFPAC cells and HDAC 7 in BXPC cells by 2-fold. No change in expression was shown in any of the cell lines on HDAC 2. This study showed that indole-3-carbinol may exert histone deacetylase inhibitory effects. Further studies are needed to confirm these results. Specific HDACs as potential targets for pancreatic cancer are growing among the scientific community. HDACs are known to be regulators of growth, differentiation and cell death and dysfunction of transcriptional repression mediated by HDACs may lead to the development of cancer. Citation Format: Beverly D. Lyn-Cook, Li Pang, Lascelles E. Lyn-Cook, Beverly Word, George Hammons. Expression of histone deacetylases (HDACs) 1, 2, 3 and 7 in pancreatic cancer cell lines: The role of indole-3-carbinol. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5376. doi:10.1158/1538-7445.AM2013-5376