Document Detail


Antitumor activity of a novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma.
MedLine Citation:
PMID:  21865079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aberrant regulation of epigenetic systems including histone acetylation contributes to inappropriate gene expression in cancer cells. In this study, we investigated the antitumor effects of the novel histone deacetylase inhibitor (S)-HDAC42 in oral squamous cell carcinoma (OSCC) cells. The antiproliferative effect of (S)-HDAC42 was multifold higher than that of suberoylanilide hydroxamic acid in a panel of oral squamous carcinoma cell lines examined. (S)-HDAC42 mediated caspase-dependent apoptosis by targeting multiple signaling pathways relevant to cell cycle progression and survival. We demonstrated that (S)-HDAC42 downregulated the levels of phospho-Akt, cyclin D1, and cyclin-dependent kinase 6, accompanied by increased p27 and p21 expression. In addition, (S)-HDAC42 suppressed NF-κB signaling by blocking tumor necrosis factor-α-induced nuclear translocation, and activated reactive oxygen species generation. Finally, (S)-HDAC42 exhibited high potency in suppressing OSCC tumor growth in a Ca922 xenograft nude mouse model. Together, these findings underscore the translational value of (S)-HDAC42 in fostering new therapeutic strategies for OSCC.
Authors:
Li-Yuan Bai; Chang-Fang Chiu; Shiow-Lin Pan; Aaron M Sargeant; Tzong-Ming Shieh; Ying-Chu Wang; Jing-Ru Weng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-23
Journal Detail:
Title:  Oral oncology     Volume:  47     ISSN:  1879-0593     ISO Abbreviation:  Oral Oncol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-28     Completed Date:  2012-02-24     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1127-33     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Carcinoma, Squamous Cell / drug therapy*
Cell Line, Tumor
Cyclin D1 / metabolism
Cyclin-Dependent Kinase 6 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Female
Histone Deacetylase Inhibitors / pharmacology*
Hydroxamic Acids / pharmacology*
Mice
Mice, Nude
Mouth Neoplasms / drug therapy*
NF-kappa B / metabolism
Phenylbutyrates / pharmacology*
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / metabolism
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects
Tumor Necrosis Factor-alpha / drug effects
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/NF-kappa B; 0/OSU-HDAC42 compound; 0/Phenylbutyrates; 0/Reactive Oxygen Species; 0/Tumor Necrosis Factor-alpha; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 149647-78-9/vorinostat; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.22/Cyclin-Dependent Kinase 6

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


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