SAHA and EGCG Promote Apoptosis in Triple-negative Breast Cancer Cells, Possibly through the Modulation of cIAP2

Abstract

Background/Aim: Inhibition of apoptosis is one of the hallmarks of cancer, and anti-apoptotic genes are often targets of genetic and epigenetic alterations. Cellular inhibitor of apoptosis 2 (cIAP2) has a role in degrading caspases by linking them to ubiquitin molecules, and is upregulated in triple-negative breast cancer (TNBC). Previous studies have demonstrated that cIAP2 may play a role in the epithelial-to-mesenchymal transition (EMT). Materials and Methods: Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was administered to triple-negative breast cancer (TNBC) cells alone or in combination with epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor isolated from green tea. Results: The compounds were able to decrease the expression of cIAP2 while increasing the expression of pro-apoptotic caspase 7. There were also changes in histone modifications, suggesting a role of epigenetic mechanisms in these changes in expression of cIAP2. These changes resulted in an increase in apoptosis. SAHA and EGCG were also capable of limiting TNBC cell migration across a fibronectin (FN) matrix. Conclusion: SAHA and EGCG reduce the metastatic potential of TNBC by inducing the apoptotic pathway.