Document Detail


Valproic acid as a therapeutic agent for head and neck squamous cell carcinomas.
MedLine Citation:
PMID:  18398612     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSES: Here we investigate if valproic acid (VA) can enhance the efficacy of commonly used therapies for head and neck squamous cell carcinomas (HNSCC) and the molecular mechanisms that may be related to its anticancer effects. METHODS: Proliferation and viability of distinct cell types subjected to VA treatment alone or in combination regimens were measured through BrdU incorporation and LDH release, respectively. Molecular markers compatible with histone deacetylase inhibitory activity of VA were assessed through western blots assays in lysates obtained from cultured cells and tumour biopsies. RESULTS: Treatment of all cell types with VA resulted in a dose-dependent increase in histone H3 acetylation and p21 expression, as well as dose-dependent cytostasis. In contrast, the cytotoxic response to VA was variable and did not correlate with cytostasis, histone acetylation or p21 induction. The variability in response to VA was also observed in tumour biopsy samples collected from patients prior to and following a 1 week oral course of VA. In addition, we found that a combination of a clinically achievable concentration of VA plus cisplatin caused a threefold to sevenfold increase in cisplatin cytotoxicity in vitro. CONCLUSIONS: VA acts as a histone deacetylase inhibitor (HDI) in SCC cells and normal human keratinocytes (HKs), potentiates the cytotoxic effect of cisplatin in SCC cell lines and decreases the viability of SCC cells as opposed to HKs. Taken together, the results provide initial evidence that VA might be a valuable drug in the development of better therapeutic regimens for HNSCC.
Authors:
Rafael B Erlich; Danny Rickwood; William B Coman; Nicholas A Saunders; Alexander Guminski
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-09
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  63     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2008-12-23     Completed Date:  2009-01-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  381-9     Citation Subset:  IM    
Affiliation:
Epithelial Pathobiology Group, Cancer Biology Programme, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia.
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Aged
Antineoplastic Agents / pharmacology,  therapeutic use*
Blotting, Western
Carcinoma, Squamous Cell / drug therapy*,  pathology
Cell Proliferation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Drug Synergism
Female
Head and Neck Neoplasms / drug therapy*,  pathology
Histones / metabolism
Humans
Keratinocytes / drug effects
Male
Middle Aged
Valproic Acid / pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Histones; 99-66-1/Valproic Acid

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


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