The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo
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BioMed Central
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Research
The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo Michael T Buckley3, Joanne Yoon1,3, Herman Yee2,3, Luis Chiriboga2,3, Leonard Liebes3, Gulshan Ara6, Xiaozhong Qian6, Dean F Bajorin5, TungTien Sun1, Xue-Ru Wu1,4 and Iman Osman*1,3 Address: 1Urology, New York University School of Medicine, New York, USA, 2Pathology, New York University School of Medicine, New York, USA, 3Medicine, New York University School of Medicine, New York, USA, 4Veterans Affairs Medical Center, New York, USA, 5Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA and 6Curagen Corporation, Branford, USA Email: Michael T Buckley - [email protected]; Joanne Yoon - [email protected]; Herman Yee - [email protected]; Luis Chiriboga - [email protected]; Leonard Liebes - [email protected]; Gulshan Ara - [email protected]; Xiaozhong Qian - [email protected]; Dean F Bajorin - [email protected]; Tung-Tien Sun - [email protected]; XueRu Wu - [email protected]; Iman Osman* - [email protected] * Corresponding author
Published: 12 October 2007 Journal of Translational Medicine 2007, 5:49
doi:10.1186/1479-5876-5-49
Received: 14 July 2007 Accepted: 12 October 2007
This article is available from: http://www.translational-medicine.com/content/5/1/49 © 2007 Buckley et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Treatment options for patients with recurrent superficial bladder cancer are limited, necessitating aggressive exploration of new treatment strategies that effectively prevent recurrence and progression to invasive disease. We assessed the effects of belinostat (previously PXD101), a novel histone deacetylase inhibitor, on a panel of human bladder cancer cell lines representing superficial and invasive disease, and on a transgenic mouse model of superficial bladder cancer. Methods: Growth inhibition and cell cycle distribution effect of belinostat on 5637, T24, J82, and RT4 urothelial lines were assessed. Ha-ras transgenic mice with established superficial bladder cancer were randomized to receive either belinostat or vehicle alone, and assessed for bladder weight, hematuria, gene expression profiling, and immunohistochemistry (IHC). Results: Belinostat had a significant linear dose-dependent growth inhibition on all cell lines (IC50 range of 1.0–10.0 µM). The 5637 cell line, which was derived from a superficial papillary tumor, was the most sensitive to treatment. Belinostat (100 mg/kg, intraperitoneal, 5 days each week for 3 weeks) treated mice had less bladder weight (p < 0.05), and no hematuria compared with 6/10 control mice that developed at least one episode. IHC of bladder tumors showed less cell prol
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