Phenylbutyrate attenuates the expression of Bcl-X-L, DNA-PK, caveolin-1, and VEGF in prostate cancer cells

Phenylbutyrate (PB) is a histone deacetylase inhibitor that has been shown to Induce differentiation and apoptosis In various cancer cell lines. Altho ugh these effects are most likely due to modulation of gene expression, the specific genes and gene products responsible for the effects of PB are not well characterized. In this study, we used cDNA expression arrays and West ern blot to assess the effect that PB has on the expression of various canc er and apoptosis-regulatory gene products. We show that PB attenuates the e xpression of the apoptosis antagonist Bcl-X-L, the double-strand break repa ir protein DNA-dependent protein kinase, the prostate progression marker ca veolin-1, and the pro-angiogenic vascular endothelial growth factor. Furthe rmore, PB was found to act in synergy with ionizing radiation to induce apo ptosis in prostate cancer cells. Taken together, our results point to the p ossibility that PS may be an effective antiprostate cancer agent when used in combination with radiation or chemotherapy and for the inhibition of can cer progression.