Abstract 2020: SAHA and EGCG affect metastatic potential to varying degrees in three triple-negative breast cancer cell lines

Although triple-negative breast cancers (TNBC) have distinct molecular aberrations, tumors of the same histological grade may have dramatically different responses to the same therapy. TNBC tumors are basal-like, aggressive, and harbor a proclivity to metastasize to the brain and lungs. By modifying the cancer epigenome we have shown it is possible to reduce the metastatic potential of triple-negative breast cancer. Suberoylanilide hydroxamic acid (SAHA, clinically Vorinostat) is a histone deacetylase (HDAC) inhibitor, and epigallocatechin-3-gallate (EGCG) is a green tea polyphenol that acts as a DNA methyltransferase (DNMT) inhibitor. In combination, we found that 3 μM SAHA and 5 μM EGCG alter mammosphere formation, and the expression of E-cadherin and N-cadherin, which are genes involved in the epithelial-to-mesenchymal transition (EMT). Epigenetic enzyme activity was also assessed to determine if SAHA and EGCG were capable of modulating the functionality of DNMTs and HDACs. Because our previous work has identified a decrease in cellular viability with the combination of SAHA and EGCG, we aimed to investigate the effect on cell cycle arrest and genes involved in cell cycle progression. Our prior findings have indicated that the combination of SAHA and EGCG decreases the expression level of miR-221/222, which is known to directly inhibit translation of p27 and PTEN. p27 is involved in regulating the transition from G1 to S phase, and with the combination of SAHA and EGCG the expression of p27 was significantly increased, suggesting potential cell cycle arrest between G1 and S phase. Because the PTEN/Akt pathway plays a role in progression from G1 to S phase through p-Akt, we also investigated changes in the expression of PTEN with SAHA and EGCG. Together our findings are reflective of tumor heterogeneity; despite the same breast cancer subtype they respond differently to chemotherapeutics. Further studies will include research into specific epigenetic modifications associated with the epithelial-like reversion seen in this project. Citation Format: Kayla A. Lewis. SAHA and EGCG affect metastatic potential to varying degrees in three triple-negative breast cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2020.