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
