Gold(III) - Dithiocarbamato complexes induce cancer cell death triggered by thioredoxin redox system inhibition and activation of ERK pathway

Daniela Saggioro, Maria Pia Rigobello, Lucia Paloschi, Alessandra Folda, Stephen A. Moggach, Simon Parsons, Luca Ronconi, Dolores Fregona, Alberto Bindoli

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Although gold compounds are now recognized as promising anticancer agents, so far only gold(I) derivatives have been investigated for this purpose, whereas the use of gold(III) complexes has been hampered by their poor stability under physiological conditions. We have therefore carried out studies on selected gold(III) anticancer agents, showing enhanced stability due to the presence of chelating dithiocarbamato ligands. We found that they induce cancer cell death through both apoptotic and nonapoptotic mechanisms. They also inhibit thioredoxin reductase activity, generate free radicals, modify some mitochondrial functions, and increase ERK1/2 phosphorylation. Based on our results, we propose and discuss a working model suggesting that deregulation of the thioredoxin reductase/thioredoxin redox system is a major mechanism involved in the anticancer activity of the investigated gold(III)-dithiocarbamato complexes.

Original languageEnglish
Pages (from-to)1128-1139
Number of pages12
JournalChemistry and Biology
Issue number10
Publication statusPublished - Oct 2007

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