The Polycomb Group (PcG) proteins are epigenetic suppressors of gene expression that play a key role in promoting cell survival. This suppression is achieved via the action of two multiprotein PcG complexes - PRC2 (eed) and PRC1 (Bmi-1). These complexes act to modulate gene expression by increasing histone methylation and reducing acetylation - ultimately leading to a closed chromatin conformation and gene silencing. Activity of these proteins is associated with increased cell proliferation and survival. We show increased expression of key PcG proteins in immortalized keratinocytes and skin cancer cell lines. We examine the role of two key PcG proteins, Bmi-1 and Ezh2, and the impact of the active agent in green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), on the function of these regulators. EGCG treatment of SCC-13 cells reduces Bmi-1 and Ezh2 level and this is associated with reduced cell survival. The reduction in survival is associated with a global reduction in histone H3-K27-trimethylation (H3 K27-3M), a hallmark of PRC2 complex action. This change in PcG protein expression is associated with reduced expression of key proteins that enhance progression through the cell cycle (cdk1, cdk2, cdk4, cyclin D1, cyclin E, cyclin A, and cyclin B1) and increased expression of proteins that inhibit cell cycle progression (p21 and p27). Apoptosis is also enhanced, as evidenced by increased caspase 9, 8 and 3 cleavage and increased PARP cleavage. EGCG treatment also increases Bax and suppresses Bcl-xL expression. Vector-mediated enhanced Bmi-1 expression reverses these EGCG-dependent changes. These findings suggest that green tea polyphenols reduce skin tumor cell survival by influencing PcG-mediated epigenetic regulatory mechanisms.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4913.