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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2007

Open Access 01-12-2007 | Research

The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo

Authors: Michael T Buckley, Joanne Yoon, Herman Yee, Luis Chiriboga, Leonard Liebes, Gulshan Ara, Xiaozhong Qian, Dean F Bajorin, Tung-Tien Sun, Xue-Ru Wu, Iman Osman

Published in: Journal of Translational Medicine | Issue 1/2007

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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 proliferation and a higher expression of p21WAF1 in the belinostat-treated mice. Gene expression profile analysis revealed 56 genes significantly different in the treated group; these included the upregulation of p21WAF1, induction of core histone deacetylase (HDAC), and cell communication genes.

Conclusion

Our data demonstrate that belinostat inhibits bladder cancer and supports the clinical evaluation of belinostat for the treatment of patients with superficial bladder cancer.
Appendix
Available only for authorised users
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Metadata
Title
The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo
Authors
Michael T Buckley
Joanne Yoon
Herman Yee
Luis Chiriboga
Leonard Liebes
Gulshan Ara
Xiaozhong Qian
Dean F Bajorin
Tung-Tien Sun
Xue-Ru Wu
Iman Osman
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2007
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-5-49

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Keynote webinar | Spotlight on medication adherence

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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