[MS-275, a histone deacetylase inhibitor, induces apoptosis and alters survivin gene expression in human myeloma cell line U266]

Abstract

Background and objective: Histone deacetylase inhibitors (HDACi) exert antitumor effects through the induction of apoptosis. This study was to investigate the effects of HDACi on survivin gene expression, cell proliferation and apoptosis in human myeloma cell line U266.

Methods: U266 cells were exposed to different concentrations of MS-275, a histone deacetylase inhibitor, at different time courses. Cell viability was measured using the trypan blue exclusion assay. Changes in cell morphology were observed with Wright-Giemsa staining. Cell cycle was analyzed using flow cytometry. Protein expressions of poly (ADP-ribose) polymerase (PARP), caspase-3, survivin, P21 and CDK4 were detected by Western blot.

Results: MS-275 inhibited the growth of U266 cells in a dose-and time-dependent manner. After exposure to 1.39 micromol/L MS-275 for 48 h, the cell cycle was arrested at the G0/G1 phase, and the cell viability was decreased by 50%. After the treatment with 2 micromol/L MS-275 for 24 h and 36 h, the ratios of U266 cells at the G0/G1 phase were increased to 66.39% and 89.80%, respectively. Obvious changes in morphology of U266 were observed under microscopy. Cleaved PARP appeared, along with an increased protein level of P21 and a decrease of survivin and CDK4 levels in U266 cells treated with MS-275.

Conclusion: MS-275 could suppress the proliferation, induce apoptosis and reduce the expression of survivin in human myeloma cell line U266, which may be associated with the down-regulation of survivin.