Metal-Binding Drugs for Cancer Therapy - Merlot, Angelica;Richardson, Des
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Under normal circumstances, cellular metal homeostasis is tightly regulated. However, in malignancies, there is evidence that tumours possess alterations in the processing of biologically important transition metal ions, e.g., iron and copper. The de-regulation of metal homeostasis in cancer cells reveals a particular vulnerability to metal-depletion, which can be manipulated therapeutically by the use of novel chelators. The chelators, Dp44mT and Bp4eT, have recently been shown to be highly effective in terms of inhibiting tumour growth. Although studies have evaluated their mechanisms of…mehr

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Produktbeschreibung
Under normal circumstances, cellular metal homeostasis is tightly regulated. However, in malignancies, there is evidence that tumours possess alterations in the processing of biologically important transition metal ions, e.g., iron and copper. The de-regulation of metal homeostasis in cancer cells reveals a particular vulnerability to metal-depletion, which can be manipulated therapeutically by the use of novel chelators. The chelators, Dp44mT and Bp4eT, have recently been shown to be highly effective in terms of inhibiting tumour growth. Although studies have evaluated their mechanisms of action, the mechanism by which these agents are initially transported into cells to induce cytotoxicity is unknown and thus was investigated herein. These studies demonstrated that 14C-Bp4eT enter cells via a non-saturable linear uptake process, suggestive of passive diffusion, while the uptake of 14C-Dp44mT was saturable, indicating a carrier/receptor-mediated transport mechanism. Moreover, investigations also demonstrated that, unlike Bp4eT, the interactions of Dp44mT with HSA enhances chelator uptake into human cancer cells, increasing drug delivery and improving its anti-tumour efficacy.
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Autorenporträt
Dr. Angelica M. Merlot,B.Med.Sci.(Hons), Ph.D., NHMRC Peter Doherty Postdoctoral Research Fellow, University of Sydney, Sydney, Australia.Prof. Des R. Richardson,B.Sc., M.Sc., Ph.D., D.Sc. (UWA), F.F.Sc., FRCPath (UK), NHMRC Senior Principal Research Fellow, Director, Molecular Pharmacology and Pathology Program, University of Sydney.