Abstract
Pathways of proliferation, apoptosis, and migration are interconnected. This crosstalk has implications in embryonic development and differentiation, as well as cancer. cIAP2 is an inhibitor of apoptosis that has the ability to indirectly activate genes involved in the epithelial-to-mesenchymal transition (EMT) through controlling ERK/MAPK, TGF-beta, and NF-kappa beta pathways. In this study we used two epigenome-modifying compounds: SAHA, which is a histone deacetylase (HDAC) inhibitor, and EGCG, which is a DNA methyltransferase (DNMT) inhibiting green tea polyphenol. We found that SAHA and EGCG were capable of reducing the migration of four breast cancer cell lines across a fibronectin (FN) matrix. Since cIAP2 can upregulate the expression of FN through TGF-beta, we also investigated the expression of cIAP2 in breast cancer cells with the treatment of SAHA and EGCG and found reduced levels of cIAP2. We conducted apoptosis assays to determine if the decrease in cIAP2 resulted in an increase in breast cancer cell apoptosis. Finally, we evaluated the effects of SAHA and EGCG on mammosphere formation. Mammospheres result when EMT is induced in immortalized or cancerous breast cells. We found that mammosphere formation decreased with the administration of SAHA and EGCG. These findings demonstrate the ability of SAHA and EGCG to reduce breast cancer cell migration while increasing apoptosis through interconnected pathways. Future studies will explore the specific epigenetic modifications associated with the decrease in cIAP2 expression.
Citation Format: Kayla A. Lewis, Trygve O. Tollefsbol. SAHA and EGCG reduce breast cancer migration, possibly through modulation of cIAP2 [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B046.
