The effects of the histone deacetylase inhibitor valproic acid on cell cycle, growth suppression and apoptosis in multiple myeloma.

The aim of this study was to evaluate the effects of valproic acid (VPA), as a histone deacetylase inhibitor, on myeloma cell lines and on sorted human bone marrow multiple myeloma cells. VPA induced accumulation of acetylated histones, potently inhibited proliferation in a dose-dependent manner and induced apoptosis in all myeloma cell lines tested as well as in sorted primary multiple myeloma cells. Cell cycle analysis indicated an arrest in G0/1 phase in response to VPA. Accumulation of p21 and reduced levels of cyclin D1 were detected. The production of vascular endothelial growth factor was significantly inhibited by VPA. These results provide the framework for clinical trials.