title: Does valproic acid induce neuroendocrine differentiation in prostate cancer?
abstract: Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. Here, we investigate whether VPA treatment induces neuroendocrine differentiation of Prostate Cancer (PCa). A tissue microarray of VPA-treated and untreated tumor xenografts and cell lines of human PCa (LNCaP, C4-2, DU145, and PC-3) were generated and were analyzed by immunohistochemical analysis (IHC) for NE markers chromogranin A (CgA), synaptophysin, and NCAM (neural cell adhesion molecule). Western blot analysis for CgA was performed to confirm the results of the TMA. IHC analysis did not reveal any induction of CgA, synaptophysin, or NCAM in any xenograft after VPA treatment in vivo. In vitro, VPA treatment induced little synaptophysin expression in C4-2 and PC-3 cells and NCAM expression in LNCaP and PC-3 cells. In the case of CgA, VPA treatment decreased its expression in vitro in a dose-dependent manner, as determined by western blot analysis. Thus our data demonstrates that VPA does not induce NE differentiation of PCa cells in the physiologically relevant in vivo setting.
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Marburg 205A, 600 North Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Sidana
authors.forename: Muwen
authors.initials: M
authors.lastname: Wang
authors.forename: Wasim H
authors.initials: WH
authors.lastname: Chowdhury
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Shabana
authors.initials: S
authors.lastname: Shabbeer
authors.forename: George
authors.initials: G
authors.lastname: Netto
authors.forename: Michael
authors.initials: M
authors.lastname: Carducci
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Lupold
authors.forename: Ronald
authors.initials: R
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D053379:Chromogranin A / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D013194:Staining and Labeling; D016708:Synaptophysin / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D053379:Chromogranin A; D019006:Neural Cell Adhesion Molecules; D016708:Synaptophysin; D014635:Valproic Acid