Abstract 2007: Epigenetic reactivation of CCN5/WISP2 by combined effect of green tea polyphenol and epigenetic modulators in highly aggressive breast cancer cells

Abstract

Abstract CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. One of the major functions of the CCN5 protein is to block aggressive behavior, such as the mesenchymal-to-epithelial transition (MET) of cancer cells. CCN5/WISP-2 is constitutively expressed in less aggressive human breast cancer cells, whereas its expression is undetected in the highly aggressive breast cancer cells. Dietary green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), is believed to be an anticancer agent in part through its regulation of epigenetic processes. Our studies were aimed to address the epigenetic mechanisms of CCN5 reactivation by EGCG in highly aggressive breast cancer cells. In our current studies, we found that EGCG can reactivate CCN5 expression in highly aggressive breast cancer cell line (MDA-MB-231) and augments mesenchymal-epithelial transition process by modulating multiple EMT regulators. Combination studies using EGCG with the epigenetic modulators including the histone deacetylase (HDAC) inhibitor, trichostatin (TSA) and the DNA methyltransferase (DNMT) inhibitor such as 5-aza-2’-deoxycytidine (5- aza), revealed a synergistic effect of reactivation of CCN5 expression in highly aggressive breast cancer cells. Our findings help to assess the key mechanisms of EGCG chemoprevention and therapy by impacting epigenetic pathways toward aggressive breast tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2007. doi:10.1158/1538-7445.AM2011-2007