Tesson, M., Anselmi, G., Bell, C. and Mairs, R. (2017) Cell cycle specific radiosensitisation by the disulfiram and copper complex. Oncotarget, 8(39), pp. 65900-65916. (doi: 10.18632/oncotarget.19539) (PMID:29029481) (PMCID:PMC5630381)
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Abstract
The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Treatment with 0.1 and 0.3 μM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c) and UVW cells, respectively. The increased potency of ionising radiation treatment induced by DSF:Cu and/or gemcitabine was determined by clonogenic assay. Treatment with 0.3 μM DSF:Cu resulted in greater radiation kill, exemplified by dose enhancement factor values of 2.64 and 2.84 in SKN-BE(2c) and UVW cells, respectively. Although DSF:Cu failed to sensitise S phase cells to irradiation, we observed that DSF:Cu radiosensitisation was potentiated by the S phase-specific cytotoxic drug gemcitabine. The efficacy of the combination treatment consisting of DSF:Cu, gemcitabine and ionising radiation was scheduledependent. Together, these results describe cell cycle specific radiosensitisation by DSF:Cu. The well-established toxicity profiles of DSF and gemcitabine should facilitate their evaluation as a combination treatment in patients undergoing radiotherapy.
Item Type: | Articles |
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Additional Information: | This work was supported by the joined Action Medical Research and Neuroblastoma UK grant GN2196. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Tesson, Dr Mathias and Mairs, Professor Robert |
Authors: | Tesson, M., Anselmi, G., Bell, C., and Mairs, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Oncotarget |
Publisher: | Impact Journals |
ISSN: | 1949-2553 |
ISSN (Online): | 1949-2553 |
Published Online: | 25 July 2017 |
Copyright Holders: | Copyright © 2017 Tesson et al. |
First Published: | First published in Oncotarget 8(39): 65900-65916 |
Publisher Policy: | Reproduced under a Creative Commons license |
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