J Appl Biomed 12:301-308, 2014 | DOI: 10.1016/j.jab.2014.04.002

Diethyldithiocarbamate complexes with metals used as food supplements show different effects in cancer cells

Jindrich Sedlacek^a,*, Luisa M.D.R.S. Martins^b,c, Petr Danek^a, Armando J.L. Pombeiro^c, Boris Cvek^a

^a Department of Cell Biology & Genetics, Palacky University, Olomouc, Czech Republic

^b Chemical Engineering Department, ISEL, Lisboa, Portugal

^c Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Technical University of Lisbon, Lisboa, Portugal

Diethyldithiocarbamate (ditiocarb), a metabolite of the old anti-alcoholic drug disulfiram (Antabuse), forms proteasome-inhibiting metal complexes with copper or zinc that suppress cancer cells both in vitro and in vivo. The drug has been used in a clinical trial (NCT00742911) along with copper gluconate as a dietary supplement in patients with cancer spreading to the liver. In this study, we demonstrate the effect of synthetic complexes of disulfiram with four various metals (Mn, Fe, Cr and Cu) used as food supplements. These complexes may be spontaneously formed in the blood during the use of disulfiram with divalent metals and thus may suppress the growth of cancer in vivo. The cytotoxic effect of the compounds and the compounds' ability to inhibit the cellular proteasome were tested in the osteosarcoma cell line U2OS. After 48 h, copper and manganese complexes exhibited cytotoxic effect on the cell line, in sharp contrast to both iron and chromium complexes.

Keywords: Disulfiram; Dietary supplements; Dithiocarbamate-metal complexes; Cancer; Proteasome; Copper; Manganese

Received: April 14, 2014; Accepted: April 16, 2014; Published: November 1, 2014  Show citation