Cell cycle specific radiosensitisation by the disulfiram and copper complex

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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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
Additional Information:This work was supported by the joined Action Medical Research and Neuroblastoma UK grant GN2196.
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 (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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