Journal article
Increasing intracellular bioavailable copper selectively targets prostate cancer cells
MA Cater, HB Pearson, K Wolyniec, P Klaver, M Bilandzic, BM Paterson, AI Bush, PO Humbert, S La Fontaine, PS Donnelly, Y Haupt
ACS Chemical Biology | AMER CHEMICAL SOC | Published : 2013
DOI: 10.1021/cb400198p
Abstract
The therapeutic efficacy of two bis(thiosemicarbazonato) copper complexes, glyoxalbis[N4-methylthiosemicarbazonato]CuII [CuII(gtsm)] and diacetylbis[N4-methylthiosemicarbazonato]CuII [Cu II(atsm)], for the treatment of prostate cancer was assessed in cell culture and animal models. Distinctively, copper dissociates intracellularly from CuII(gtsm) but is retained by CuII(atsm). We further demonstrated that intracellular H2gtsm [reduced Cu II(gtsm)] continues to redistribute copper into a bioavailable (exchangeable) pool. Both CuII(gtsm) and CuII(atsm) selectively kill transformed (hyperplastic and carcinoma) prostate cell lines but, importantly, do not affect the viability of primary prostate..
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Funding Acknowledgements
This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC) (M.A.C., A.I.B., P.S.D., S.L., and Y.H.), the CASS Foundation (M.A.C.), the Australian Research Council (ARC) (P.S.D.), the Prostate Cancer Foundation of Australia (MAC., Y.H.), the VESKI award (Y.H.), and the Victorian Cancer Agency (CAPTIV) (Y.H.). We thank J. Camakaris (University of Melbourne) for providing reagents and J. Finnie, Senior Veterinary Pathologist (University of Adelaide) for histopathological examinations. We also thank K Hale and L. Dawes from the Peter MacCallum Animal Facility for technical support.