The role and possible molecular mechanism of valproic acid in the growth of MCF-7 breast cancer cells

Aim To investigate the role of valproic acid (VPA), a class I selective histone deacetylase inhibitor, on Michigan Cancer Foundation (MCF)-7 breast cancer cells, named and explore its possible molecular mechanism. Methods MCF-7 cells were cultured with sodium valproate (0.5-4.0 mmol/L) for 24 h, 48 h, and 72 h in vitro, respectively. The cell viability, apoptosis, and cell cycle were examined. The activities and protein expressions of caspase-3, caspase-8, and caspase-9 were subsequently assayed. Finally, mRNA and protein expressions of cyclin A, cyclin D1, cyclin E, and p21 were analyzed. Results Sodium valproate suppressed MCF-7 cell growth, induced cell apoptosis, and arrested G1 phase in a time- and concentration-dependent manner, with the relative cell viabilities decreased, cell apoptosis ratios increased, and percentage of G1 phase enhanced (P < 0.05). Increased activity of caspase-3 and caspase-9, but not caspase-8, and increased protein levels were found under sodium valproate (2.0 mmol/L, 48h). P21 was up-regulated and cyclin D1 was down-regulated at both mRNA and protein levels under sodium valproate (2.0 mmol/L, 48h)(P < 0.05), although cyclin E and cyclin A remained changed. Conclusion These results indicate that VPA can suppress the growth of breast cancer MCF-7 cells by inducing apoptosis and arresting G1 phase. Intrinsic apoptotic pathway is dominant for VPA-induced apoptosis. For G1 phase arrest, p21 up-regulation and down-regulation of cyclin D1 may be the main molecular mechanism.