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. Although 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 Western blot to assess the effect that PB has on the expression of various cancer and apoptosis-regulatory gene products. We show that PB attenuates the expression of the apoptosis antagonist Bcl-X(L), the double-strand break repair protein DNA-dependent protein kinase, the prostate progression marker caveolin-1, and the pro-angiogenic vascular endothelial growth factor. Furthermore, PB was found to act in synergy with ionizing radiation to induce apoptosis in prostate cancer cells. Taken together, our results point to the possibility that PB may be an effective anti-prostate cancer agent when used in combination with radiation or chemotherapy and for the inhibition of cancer progression.
Goh
M
M
Section of Urology, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0396, USA.
Chen
F
F
Paulsen
M T
MT
Yeager
A M
AM
Dyer
E S
ES
Ljungman
M
M
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D003035:Cobalt / Q000494:pharmacology; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000502:physiology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010654:Phenylbutyrates / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009687:Nuclear Proteins; D010654:Phenylbutyrates; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051020:bcl-X Protein; D003035:Cobalt; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C018021:cobaltous chloride