Recommend Epigenetics to your librarian today. Download form here.
Sign up for Table of Contents Alerts.
The official journal of the Epigenetics Society.
Email this page
Print this page
Short Report
The Epigenetic Modifier, Valproic Acid, Enhances Radiation Sensitivity
Tom C. Karagiannis, Harikrishnan Kn and Assam El-Osta
volume 1 | issue 3
july/august/september 2006Pages: 131 - 137
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
Valproic acid is an established therapeutic for a variety of seizure disorders and in
certain cases for depression and anxiety. In addition, valproic acid has been shown to
possess histone deacetylase inhibition activity and is currently being investigated as
an anti-cancer agent, either alone or in combination with other conventional cancer
therapies such as ionizing radiation. In this study, we investigated whether valproic
acid modulates cellular responses to radiation in human erythroleukemic, K562 cells.
Hyperacetylation of nuclear histones 3 and 4 was used to correlate the effects of
valproic acid to inhibition of histone deacetylase activity, clonogenic survival,
apoptosis and apoptosis. The findings from the clonogenic survival and caspase
induction assays indicated that pre-treatment of cells with valproic acid for 24 hours,
markedly enhanced radiation induced cell-death and apoptosis in K562 cells,
respectively. Mechanisms involving drug-mediated cytotoxicity and changes in cell
cycle distribution were associated with the radiation sensitizing properties of valproic
acid, particularly at the higher concentrations. Overall, our findings are consistent
with the general consensus that HDAC inhibitors efficiently sensitize cancer cells to
the effects of ionizing radiation and support the idea of developing clinically relevant
combinations of HDAC inhibitors and radiotherapy.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.