The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo
<p>Abstract</p> <p>Background</p> <p>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 assess...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-10-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/5/1/49 |
| _version_ | 1828358879528878080 |
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| author | Liebes Leonard Chiriboga Luis Yee Herman Yoon Joanne Buckley Michael T Ara Gulshan Qian Xiaozhong Bajorin Dean F Sun Tung-Tien Wu Xue-Ru Osman Iman |
| author_facet | Liebes Leonard Chiriboga Luis Yee Herman Yoon Joanne Buckley Michael T Ara Gulshan Qian Xiaozhong Bajorin Dean F Sun Tung-Tien Wu Xue-Ru Osman Iman |
| author_sort | Liebes Leonard |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Growth inhibition and cell cycle distribution effect of belinostat on 5637, T24, J82, and RT4 urothelial lines were assessed. Ha-<it>ras </it>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).</p> <p>Results</p> <p>Belinostat had a significant linear dose-dependent growth inhibition on all cell lines (IC<sub>50 </sub>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 p21<sup>WAF1 </sup>in the belinostat-treated mice. Gene expression profile analysis revealed 56 genes significantly different in the treated group; these included the upregulation of p21<sup>WAF1</sup>, induction of core histone deacetylase (HDAC), and cell communication genes.</p> <p>Conclusion</p> <p>Our data demonstrate that belinostat inhibits bladder cancer and supports the clinical evaluation of belinostat for the treatment of patients with superficial bladder cancer.</p> |
| first_indexed | 2024-04-14T03:34:38Z |
| format | Article |
| id | doaj.art-551d122fe3fe4bc7a4fa6871d4ca6f8a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-14T03:34:38Z |
| publishDate | 2007-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-551d122fe3fe4bc7a4fa6871d4ca6f8a2022-12-22T02:14:49ZengBMCJournal of Translational Medicine1479-58762007-10-01514910.1186/1479-5876-5-49The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivoLiebes LeonardChiriboga LuisYee HermanYoon JoanneBuckley Michael TAra GulshanQian XiaozhongBajorin Dean FSun Tung-TienWu Xue-RuOsman Iman<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Growth inhibition and cell cycle distribution effect of belinostat on 5637, T24, J82, and RT4 urothelial lines were assessed. Ha-<it>ras </it>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).</p> <p>Results</p> <p>Belinostat had a significant linear dose-dependent growth inhibition on all cell lines (IC<sub>50 </sub>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 p21<sup>WAF1 </sup>in the belinostat-treated mice. Gene expression profile analysis revealed 56 genes significantly different in the treated group; these included the upregulation of p21<sup>WAF1</sup>, induction of core histone deacetylase (HDAC), and cell communication genes.</p> <p>Conclusion</p> <p>Our data demonstrate that belinostat inhibits bladder cancer and supports the clinical evaluation of belinostat for the treatment of patients with superficial bladder cancer.</p>http://www.translational-medicine.com/content/5/1/49 |
| spellingShingle | Liebes Leonard Chiriboga Luis Yee Herman Yoon Joanne Buckley Michael T Ara Gulshan Qian Xiaozhong Bajorin Dean F Sun Tung-Tien Wu Xue-Ru Osman Iman The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo Journal of Translational Medicine |
| title | The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo |
| title_full | The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo |
| title_fullStr | The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo |
| title_full_unstemmed | The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo |
| title_short | The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo |
| title_sort | histone deacetylase inhibitor belinostat pxd101 suppresses bladder cancer cell growth in vitro and in vivo |
| url | http://www.translational-medicine.com/content/5/1/49 |
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