title: Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells.
abstract: We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA. mlin@unmc.edu
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chou
authors.forename: Nagendra K
authors.initials: NK
authors.lastname: Chaturvedi
authors.forename: Shougiang
authors.initials: S
authors.lastname: Ouyang
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Lin
authors.forename: Dharam
authors.initials: D
authors.lastname: Kaushik
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Isaac
authors.initials: I
authors.lastname: Kim
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Lin
mesh_terms: D000135:Acid Phosphatase; D000970:Antineoplastic Agents / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000135:Acid Phosphatase; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D017027:Protein Tyrosine Phosphatases; D018719:Erb-b2 Receptor Tyrosine Kinases; D014635:Valproic Acid; C428439:prostatic acid phosphatase