Valproic acid as a therapeutic agent for head and neck squamous cell carcinomas

Erlich, Rafael B., Rickwood, Danny, Coman, William B., Saunders, Nicholas A. and Guminski, Alexander (2009) Valproic acid as a therapeutic agent for head and neck squamous cell carcinomas. Cancer Chemotherapy and Pharmacology, 63 3: 381-389. doi:10.1007/s00280-008-0747-1

Author Erlich, Rafael B.
Rickwood, Danny
Coman, William B.
Saunders, Nicholas A.
Guminski, Alexander
Title Valproic acid as a therapeutic agent for head and neck squamous cell carcinomas
Journal name Cancer Chemotherapy and Pharmacology   Check publisher's open access policy
ISSN 0344-5704
Publication date 2009-02-01
Year available 2008
Sub-type Article (original research)
DOI 10.1007/s00280-008-0747-1
Open Access Status Not yet assessed
Volume 63
Issue 3
Start page 381
End page 389
Total pages 9
Place of publication New York , U.S.A.
Publisher Springer
Language eng
Subject C1
111204 Cancer Therapy (excl. Chemotherapy and Radiation Therapy)
920102 Cancer and Related Disorders
Abstract 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. 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. 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. 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.
Keyword Valproic acid
Histone-deacetylase inhibitor
Combination therapy
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 455929
Institutional Status UQ
Additional Notes Received: 17 January 2008 Accepted: 17 March 2008 Published online: 9 April 2008

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 01 Apr 2009, 21:33:23 EST by Kylie Hengst on behalf of UQ Diamantina Institute