Histone deacetylase inhibitor suberoyl bis-hydroxamic acid suppresses cell proliferation and induces apoptosis in breast cancer cells

Abstract

Suberoyl bis-hydroxamic acid (SBHA) is a histone deacetylase inhibitor that has shown anticancer activity against numerous types of human cancer. The aim of the current study was to explore the effects of SBHA on the proliferation and apoptosis of breast cancer cells. MCF-7 breast cancer cells were treated with different concentrations of SBHA and tested for cell viability, apoptosis and gene expression changes. The results showed that SBHA significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner, as determined using a Cell Counting kit-8 assay. SBHA-treated MCF-7 cells showed G0/G1 cell-cycle arrest, coupled with elevated expression levels of p21 and p27 proteins. Hoechst 33258 staining revealed cell shrinkage, chromosomal condensation and nuclear fragmentation in MCF-7 cells treated with SBHA. Flow cytometric analysis of Annexin V-stained cells showed that SBHA treatment induced apoptotic cell death in a concentration-dependent manner. Western blot analysis confirmed the upregulation of Bax and the downregulation of Bcl-2 by SBHA. In conclusion, these results indicate that SBHA exerts cytotoxic effects against human breast cancer cells, which involves the modulation of p21, p27 and Bcl-2 family proteins, consequently leading to cell-cycle arrest and apoptosis.