Document Detail


Combination of suberoylanilide hydroxamic acid and ritonavir is effective against renal cancer cells.
MedLine Citation:
PMID:  20630573     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To investigate the combined effect of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) and the protease inhibitor ritonavir on renal cancer cells. METHODS: Renal cancer cells (769P, 786O, A498, ACHN, Caki-1) and renal proximal tubule epithelial cells were treated with SAHA (0-5 μM) with or without ritonavir (0-50 μM). Cell viability, clonogenecity, and changes in cell cycle were evaluated. The expression of acetylated histone, retinoblastoma protein (Rb), phosphorylated Rb, histone deacetylases, X-linked inhibitor of apoptosis, survivin, and active caspase 3 was assessed using Western blot analysis. RESULTS: SAHA induced histone acetylation and Rb dephosphorylation and inhibited cell growth in a time- and dose-dependent manner. SAHA and ritonavir combined inhibited cell proliferation effectively and promoted histone acetylation and Rb dephosphorylation but only slightly affected renal proximal tubule epithelial cell survival. The combination induced the accumulation of the sub-G(1) fraction, decreased the expression of X-linked inhibitor of apoptosis and survivin, and increased active caspase 3, thus inducing apoptosis. It also inhibited the expression of histone deacetylases. CONCLUSIONS: Combination therapy using SAHA and ritonavir inhibited the proliferation of renal cancer cells effectively, perhaps by inhibiting both histone deacetylase function and expression. It might be a useful new regimen for treating renal cancer.
Authors:
Akinori Sato; Takako Asano; Akio Horiguchi; Keiichi Ito; Makoto Sumitomo; Tomohiko Asano
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Publication Detail:
Type:  Journal Article     Date:  2010-07-13
Journal Detail:
Title:  Urology     Volume:  76     ISSN:  1527-9995     ISO Abbreviation:  Urology     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366151     Medline TA:  Urology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  764.e7-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan. zenpaku@ndmc.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / administration & dosage*
Drug Screening Assays, Antitumor
Drug Therapy, Combination
HIV Protease Inhibitors / administration & dosage*
Hydroxamic Acids / administration & dosage*
Kidney Neoplasms / drug therapy*,  pathology
Ritonavir / administration & dosage*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/HIV Protease Inhibitors; 0/Hydroxamic Acids; 0/Ritonavir; 149647-78-9/vorinostat

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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