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Histone deacetylase inhibitors (HDACis) have shown significant antiproliferativeand apoptotic properties in various types of cancer cells, including prostatecancer cells, and are therefore being evaluated as a treatment modality. However,the mechanism by which sodium butyrate (SB) induces apoptosis is not completelyunderstood. We focused on SB which exists in the intestine and is therefore expectedto have less adverse effects. In this study, three prostate cancer cell lines(LNCaP, DU145 and PC-3) were treated in vitro with different concentrations ofSB. Cell proliferation was studied by the XTT assay; cell cycle analysis and inductionof apoptosis were studied by laser scanning cytometry. Western blot analysis wasused to study p21, p27, CDK2, CDK4, CDK6, caspase-3, caspase-7, Fas, FADD, TRADD,Bcl-2 and Bax protein expression. SB inhibited cell growth and induced apoptosisin a concentration-dependent manner in human prostate cancer cells (LNCaP, DU145and PC-3). Western blot analysis showed dose-dependent increases of p21 levelsin DU145 and PC-3 cells, and dose-dependent decreases of CDK2, CDK4, CDK6 andprocaspase-3 protein levels in all three prostate cancer cell lines. Bcl-xL wassignificantly down-regulated in DU145 cells, and Bcl-2 was significantly down-regulatedin PC-3 and LNCaP cells. No significant changes were observed in procaspase-7,TRADD and Bax expression, although slight decreases in Fas and FADD expressionwere seen in all three prostate cancer cell lines. Analysis of cell morphologyusing laser scanning microscopy detected condensed and fragmented nuclei. In conclusion,SB induces G1 and G2 arrest by increasing p21 expression resulting in CDK2, CDK4and CDK6 down-regulation. SB potently induced apoptosis, which was accompaniedby DNA fragmentation, down-regulated Bcl-2 in LNCaP and PC-3 cells, Bcl-xL inDU145 cells, and down-regulated procaspase-3, but not procaspase-7, in these humanprostate cancer cell lines. These results suggest that SB may serve as a new modalityfor the treatment of hormone refractory prostate cancer.

Growth of human prostate cancer cells is significantly suppressed in vitro with sodium butyrate through apoptosis