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Journal of Biomedicine and Biotechnology
Volume 2011, Article ID 607480, 10 pages
http://dx.doi.org/10.1155/2011/607480
Research Article

Does Valproic Acid Induce Neuroendocrine Differentiation in Prostate Cancer?

1James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Marburg 205A, 600 North Wolfe Street, Baltimore, MD- 21287, USA
2Minimally Invasive Urologic Center, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250100, China
3Department of Pathology, Johns Hopkins University School of Medicine, 600 Wolfe Street, Baltimore, MD 21287, USA
4Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 401 North Broadway, Baltimore, MD 21231, USA

Received 3 June 2010; Revised 28 September 2010; Accepted 30 September 2010

Academic Editor: Christian Seiser

Copyright © 2011 Abhinav Sidana et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.