SB939 efficiently induce breast cell lines cycle arrest and apoptosis and the mechanism

Objective To investigate the effects of SB939,a potent histone deacetylase (HDAC)inhibitor,on proliferation,cycle arrest and apoptosis of breast cancer cell lines T47D and MDA-MB-231 in vitro and its potential regulating mechanism.Methods Cells were treated with different concentrations of SB939.Cell proliferation was measured by using methyl thiazol tetrazolium (MTT) assay.Cell cycle rate was examined by proliferation index (PI) staining.Apoptotic rate of cells were detected by Annexin V/PIdouble-staining.The expression of proteins,such as poly ADP-ribose polymerase (PARP),were analyzed by Western blotting.The mRNA level of p21 and Cyclin B1 were detected by Real-time polymerase chain reaction (Real-time PCR).Results Along with the increase of SB939 concentration,the inhibition of SB939 on T47D and MDA-MB-231 cell proliferation were obvious enhancement 50％ inhibitory concentration ( IC50 ) were (2.721 ± 0.320 ),(5.647 ± 0.470) μmol/L; Flow cytometry showed cells in G2/M phase significantly increased ( P＜0.05).After cells exposed to SB939 ( 1 μmol/L) for 24 h,G2/Mphase rates were ( 21.20 ± 1.90 ) ％,( 28.35 ± 2.25 ) ％.The rates of apoptotic cells were ( 37.60 ±1.34 ) ％,( 34.40 ± 1.77 ) ％,significantly increased as compared to the control cells ( P ＜ 0.05 ); Western blotting showed that the expression of cleaved PARP,bax and p21 were increased while B lymphocytes/leukemia-2 ( bcl-2),cdc2,Cyclin B 1 were down-regulated; The Real-time PCR suggested that the relative mRNA level of p21 was increased and Cyclin B1 was decreased.Conclusion SB939 in vitro can significantly inhibit proliferation,induce cell cycle arrest and apoptosis on breast cancer cell lines,which was in a dose-dependent manner. Key words: Breast Neoplasms; Cell cycle; Apoptosis