Dithiocarbamate-based coordination compounds as potent proteasome inhibitors in human cancer cells

Daniela      Buac; Sara      Schmitt; George      Ventro; Fathima      Rani Kona; Q.      Ping Dou

Abstract

Dithiocarbamates are a class of metal-chelating compounds with various applications in medicine. They have been used for the treatment of bacterial and fungal infections, possible treatment of AIDS, and most recently cancer. Their anti-tumor effects can in part be attributed to their ability to complex tumor cellular copper, leading to binding to and inhibition of the proteasome and in turn initiating tumor cell-specific apoptosis. Current chemotherapeutic agents are highly toxic and therefore their efficacy in the eradication of tumors is greatly limited. As a result many scientists have joined the quest for novel targeted therapies in hopes of reducing toxicity while maximizing potency and proteasome inhibition has become an attractive therapy in this regard. Here we discuss the origins, mechanism, and evolution of dithiocarbamates as potent proteasome inhibitors and therefore anti-cancer agents.

Keywords: Cancer therapy, Ubiquitin-Proteasome System, Apoptosis, Metal Complexes, Disulfiram, Antabuse, Proteasome inhibitors, UPS inhibitors.