The effect of valproic acid in combination with irradiation and temozolomide on primary human glioblastoma cells

Hosein, Abdel Nasser, Lim, Yi Chieh, Day, Bryan, Stringer, Brett, Rose, Stephen, Head, Richard, Cosgrove, Leah, Sminia, Peter, Fay, Michael and Martin, Jennifer H. (2015) The effect of valproic acid in combination with irradiation and temozolomide on primary human glioblastoma cells. Journal of Neuro-Oncology, 122 2: 263-271. doi:10.1007/s11060-014-1713-x


Author Hosein, Abdel Nasser
Lim, Yi Chieh
Day, Bryan
Stringer, Brett
Rose, Stephen
Head, Richard
Cosgrove, Leah
Sminia, Peter
Fay, Michael
Martin, Jennifer H.
Title The effect of valproic acid in combination with irradiation and temozolomide on primary human glioblastoma cells
Journal name Journal of Neuro-Oncology   Check publisher's open access policy
ISSN 0167-594X
1573-7373
Publication date 2015-04
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s11060-014-1713-x
Volume 122
Issue 2
Start page 263
End page 271
Total pages 9
Place of publication Springer New York
Publisher New York, NY United States
Collection year 2016
Language eng
Abstract Glioblastoma multiforme (GBM) has nearly uniformly fatal with a median survival of less than 2 years. While there have not been any novel anti-GBM therapeutics approved for many years, there has been the gradual accumulation of clinical data suggesting that the widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong survival in GBM patients. This pre-clinical study aimed to determine the potential clinical utility of VPA in the treatment of GBM. Primary GBM cells were treated with VPA as a monotherapy and in combination with temozolomide and irradiation. At clinically achievable concentrations, VPA was shown to be effective as a monotherapy agent in the five primary lines tested. VPA was then used as a sensitizing agent to in vitro radiation and showed significant augmentation of in vitro irradiation therapy. In addition, when VPA, radiation and temozolomide were combined an additive, rather than synergistic effect was noted. Gene expression profiling demonstrated close clustering of triple treated cells with VPA mono-treated cells while untreated cells clustered closer with TMZ-irradiation dual treated cells. These microarray data suggest a dominant role of VPA at the gene expression level when combining these different treatment options. Moreover, in an in vivo tumor transplantation model, we were able to demonstrate an increase in animal survival when cells were pre-treated with irradiation-VPA and when triple treated. These findings provide a significant rationale for the investigation of VPA in the treatment of GBM patients.
Keyword Glioblastoma
Valproic acid
Radiosensitisation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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