Cu-DEDC and Cu-PDTC (DEDC = diethyl-dithiocarbamate; PDTC = pyrrolidine-dithiocarbamate) are interesting complexes displaying potent proteasome-inhibitory and apoptosis-inducing activities. Using the corresponding 64Cu-labeled compound, as chemical probes, we investigated the accumulation of these 64Cu-complexes in human normal (HEK293) and cancer (MCF-7) cells under a range of conditions, working both in carrier-added (64Cu/Cu) and carrier-free conditions (64Cu). Selective accumulation of the 64Cu-complexes was found in tumour cells. For both 64Cu-complexes a linear increase of the %cell-uptake was observed and did not reach a plateau even in carrier-added conditions where high concentration of compounds (100 ?M) was used. No variation of the %cell-uptake was observed in temperature-dependent experiments suggesting for these compounds a passive uptake mechanism. The complexes were effluxed from the cells in the form of ionic Cu. These data clearly support the model in which the ligand acts as an ionophore for the metal ion. Actually, the intracellular metal accumulation is maximized when the cells were treated with the Cu-complexes; copper and ligand follow different uptake kinetics and reach different intracellular concentrations. Thus, copper overload originated by the complex dissociation was responsible for the cytotoxic effects. This research was supported by MIUR (PRIN 20097FJHPZ-004 and FIRB RBAP114AMK "RINAME").
Cu-64-dithiocarbamate compounds for theragnostic applications: Preliminary in-vitro studies
Salvarese N;Bolzati C
2014
Abstract
Cu-DEDC and Cu-PDTC (DEDC = diethyl-dithiocarbamate; PDTC = pyrrolidine-dithiocarbamate) are interesting complexes displaying potent proteasome-inhibitory and apoptosis-inducing activities. Using the corresponding 64Cu-labeled compound, as chemical probes, we investigated the accumulation of these 64Cu-complexes in human normal (HEK293) and cancer (MCF-7) cells under a range of conditions, working both in carrier-added (64Cu/Cu) and carrier-free conditions (64Cu). Selective accumulation of the 64Cu-complexes was found in tumour cells. For both 64Cu-complexes a linear increase of the %cell-uptake was observed and did not reach a plateau even in carrier-added conditions where high concentration of compounds (100 ?M) was used. No variation of the %cell-uptake was observed in temperature-dependent experiments suggesting for these compounds a passive uptake mechanism. The complexes were effluxed from the cells in the form of ionic Cu. These data clearly support the model in which the ligand acts as an ionophore for the metal ion. Actually, the intracellular metal accumulation is maximized when the cells were treated with the Cu-complexes; copper and ligand follow different uptake kinetics and reach different intracellular concentrations. Thus, copper overload originated by the complex dissociation was responsible for the cytotoxic effects. This research was supported by MIUR (PRIN 20097FJHPZ-004 and FIRB RBAP114AMK "RINAME").I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
