Gold(III) complexes sensitize mitochondria of tumor cells to permeability transition

The unquestionable therapeutic success of the anticancer drug cis-platin and its second- and third-generation analogues has triggered, during the past fifty years, the development of several metal-based potential chemotherapeutic drugs. Among all, gold complexes of the type [AuX2(dtc)] (X = Cl, Br; dtc = various dithiocarbamates), have been gaining increasing attention due to their capability to strongly inhibit tumor cells growth by exploiting mechanisms of action different from those recognized for the clinically-established platinum drugs. As known, survival of tumor cells is favored by mitochondrial changes that make death induction harder in a variety of stress conditions. These changes likely involve mitochondria, and include the inhibition of permeability transition pore (PTP) opening through a variety of kinase signaling pathways. Here, we present new biological findings for gold(III)-containing molecules showing a potent anticancer activity coupled with a peculiar selectivity toward cancer cells. The gold(III)-complexes are able to induce oxidative stress and tumor cell death favoring the PTP opening. Therefore, they target a specific hallmark of cancer cells, such as the resistance to apoptosis. These findings pave the way for a novel strategy allowing to hit crucial mechanisms that shield the neoplasms from the toxicity of many anti-tumor strategies, and identify the gold(III)-dithiocarbamates as a promising chemotherapeutic drugs.