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Radiosensitisation of glioblastoma cells using a histone deacetylase inhibitor (SAHA) comparing carbon ions with X-rays

Barazzuol, L, Jeynes, JCG, Merchant, MJ, Wera, AC, Barry, M, Kirkby, Karen and Suzuki, M (2014) Radiosensitisation of glioblastoma cells using a histone deacetylase inhibitor (SAHA) comparing carbon ions with X-rays International Journal of Radiation Biology, 91 (1). pp. 90-98.

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Abstract

Purpose: Prognosis for patients with glioblastoma (GBM) remains poor, and new treatments are needed. Here we used a combination of two novel treatment modalities: Carbon ions and a histone deacetylase inhibitor (HDACi). We compared these to conventional X-rays, measuring the increased effectiveness of carbon ions as well as radiosensitization using HDACi. Materials and methods: Suberoylanilide hydroxamic acid (SAHA) was used at a non-toxic concentration of 0.5 mM in combination with 85 keVum-1 carbon ions, and 250 kVp X-rays for comparison. Effects were assayed using clonogenic survival, gH2AX foci repair kinetics and measuring chromatin decondensation. Results: Dose toxicity curves showed that human GBM LN18 cells were more sensitive to SAHA compared to U251 cells at higher doses, but there was little effect at low doses. When combined with radiation, clonogenic assays showed that the Sensitizer Enhancement Ratio with carbon ions at 50% survival (SER50) was about 1.2 and 1.5 for LN18 and U251, respectively, but was similar for X-rays at about 1.3. The repair half-life of gH2AX foci was slower for cells treated with SAHA and was most noticeable in U251 cells treated with carbon ions where after 24 h, more than double the number of foci remained in comparison to the untreated cells. Hoechst fluorescent dye incorporation into the nucleus showed significant chromatin decondensation and den- sity homogenization with SAHA treatment for both cell lines. Conclusion: Our results suggest a vital role of histone deacety- lases (HDAC) in the modulation of DNA damage response and support the use of SAHA for the treatment of GBM through the combination with heavy ion therapy.

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences > Electronic Engineering
Authors :
NameEmailORCID
Barazzuol, LUNSPECIFIEDUNSPECIFIED
Jeynes, JCGUNSPECIFIEDUNSPECIFIED
Merchant, MJUNSPECIFIEDUNSPECIFIED
Wera, ACUNSPECIFIEDUNSPECIFIED
Barry, MUNSPECIFIEDUNSPECIFIED
Kirkby, KarenK.Kirkby@surrey.ac.ukUNSPECIFIED
Suzuki, MUNSPECIFIEDUNSPECIFIED
Date : 21 July 2014
Identification Number : 10.3109/09553002.2014.946111
Copyright Disclaimer : This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Radiation Biology on 21 July 2014, available online: http://www.tandfonline.com/10.3109/09553002.2014.946111
Depositing User : Jonathan Jeynes
Date Deposited : 25 Feb 2015 18:05
Last Modified : 04 Aug 2017 12:46
URI: http://epubs.surrey.ac.uk/id/eprint/805781

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