Document Detail


Histone deacetylase inhibition and blockade of the glycolytic pathway synergistically induce glioblastoma cell death.
MedLine Citation:
PMID:  18483381     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: High-grade gliomas are difficult to treat due to their location behind the blood-brain barrier and to inherent radioresistance and chemoresistance. EXPERIMENTAL DESIGN: Because tumorigenesis is considered a multistep process of accumulating mutations affecting distinct signaling pathways, combinations of compounds, which inhibit nonoverlapping pathways, are being explored to improve treatment of gliomas. Histone deacetylase inhibitors (HDI) have proven antitumor activity by blocking cell proliferation, promoting differentiation, and inducing tumor cell apoptosis. RESULTS: In this report, we show that the HDIs trichostatin A, sodium butyrate, and low nanomolar doses of LAQ824 combined with the glycolysis inhibitor 2-deoxy-d-glucose induce strong apoptosis in cancer cell lines of brain, breast, and cervix in a p53-independent manner. HDIs up-regulate p21, which is blocked by concomitant administration of 2-deoxy-d-glucose. CONCLUSIONS: We propose simultaneous blockade of histone deacetylation and glycolysis as a novel therapeutic strategy for several major cancers.
Authors:
Vivian Egler; Serdar Korur; Mike Failly; Jean-Louis Boulay; Roland Imber; Maria M Lino; Adrian Merlo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  14     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-16     Completed Date:  2008-08-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3132-40     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Neuro-oncology, Department of Research and Surgery, University Hospitals, Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects*
Brain Neoplasms / drug therapy*
Butyrates / pharmacology
Cell Line, Tumor
Deoxyglucose / pharmacology
Drug Synergism
Enzyme Inhibitors / pharmacology
Glioblastoma / drug therapy*
Glycolysis / drug effects*
Histone Deacetylase Inhibitors*
Histone Deacetylases / drug effects
Humans
Hydroxamic Acids / pharmacology
Chemical
Reg. No./Substance:
0/Butyrates; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/LAQ824; 154-17-6/Deoxyglucose; 58880-19-6/trichostatin A; EC 3.5.1.98/Histone Deacetylases

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


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