Document Detail


Does valproic acid induce neuroendocrine differentiation in prostate cancer?
MedLine Citation:
PMID:  20981253     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Abhinav Sidana; Muwen Wang; Wasim H Chowdhury; Antoun Toubaji; Shabana Shabbeer; George Netto; Michael Carducci; Shawn E Lupold; Ronald Rodriguez
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Publication Detail:
Type:  Journal Article     Date:  2010-10-25
Journal Detail:
Title:  Journal of biomedicine & biotechnology     Volume:  2011     ISSN:  1110-7251     ISO Abbreviation:  J. Biomed. Biotechnol.     Publication Date:  2011  
Date Detail:
Created Date:  2010-10-28     Completed Date:  2011-06-02     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101135740     Medline TA:  J Biomed Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  607480     Citation Subset:  IM    
Affiliation:
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Marburg 205A, 600 North Wolfe Street, Baltimore, MD 21287, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects*
Cell Line, Tumor
Chromogranin A / metabolism
Humans
Male
Mice
Mice, Nude
Neural Cell Adhesion Molecules / metabolism
Neuroendocrine Cells / pathology*
Prostatic Neoplasms / metabolism,  pathology*
Staining and Labeling
Synaptophysin / metabolism
Valproic Acid / pharmacology*
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Chromogranin A; 0/Neural Cell Adhesion Molecules; 0/Synaptophysin; 99-66-1/Valproic Acid
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