Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells

Author(s): Zdenek Skrott, Boris Cvek

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 12 , Issue 12 , 2012

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Abstract:

The idea of “repurposing” of existing drugs provides an effective way to develop and identify new therapies. Disulfiram (Antabuse), a drug commonly used for the treatment of alcoholism, shows promising anticancer activity in both preclinical and clinical studies. In the human body, disulfiram is rapidly converted to its reduced metabolite, diethyldithiocarbamate. If copper ions are available, a bis(diethyldithiocarbamate)-copper(II) complex is formed. Disulfiram´s selective anticancer activity is attributed to the copper(II) complex´s ability to inhibit the cellular proteasome. It is assumed that the complex inhibits the proteasome by a mechanism that is distinct to the clinically used drug bortezomib, targeting the 19S rather than the 20S proteasome. This difference could be explained by inhibition of the JAMM domain of the POH1 subunit within the lid of the 19S proteasome.

Keywords: Breast cancer, Copper, Disulfiram, JAMM domain, Proteasome.

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Article Details

VOLUME: 12
ISSUE: 12
Year: 2012
Published on: 03 September, 2012
Page: [1184 - 1192]
Pages: 9
DOI: 10.2174/138955712802762068
Price: $65

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