Disulfiram, Metals, and Melanoma

摘要

Melanoma is one of the deadliest types of cancer, having ahigh recurrence rate but no effective chemotherapy (1, 2). It isthe eighth most common U.S. malignancy, and recent years haveseen significant increases in the incidence rate of melanoma andespecially of early stage melanomas (3-6). Disulfiram (DSF) isan FDA-approved drug used in alcohol-aversion therapy forover 50 years (Figure 1); it is a potent inhibitor of aldehydedehydrogenase and people treated with this drug have a violentand noxious reaction upon imbibing alcoholic spirits (7). Recent reports from several labs have shown DSF to have high andselective toxicity towards melanoma cancer in vitro (8, 9). Cellviability studies show that this toxicity is dependent on the pres-ence of metal ions and suggests that the active agent is likely a Cucomplex, bis(diethyldithiocarbamate)Cu(II) or Cu(deDTC)_2,which is formed in situ (10).