Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22931589
DOI
10.2174/138955712802762068
PII: MRMC-EPUB-20120827-9
Knihovny.cz E-resources
- MeSH
- Bortezomib MeSH
- Ditiocarb chemistry MeSH
- Proteasome Inhibitors chemistry pharmacology therapeutic use MeSH
- Coordination Complexes chemistry pharmacology therapeutic use MeSH
- Boronic Acids chemistry pharmacology therapeutic use MeSH
- Humans MeSH
- Copper chemistry MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms drug therapy metabolism pathology MeSH
- Oxidative Stress drug effects MeSH
- Proteasome Endopeptidase Complex chemistry metabolism MeSH
- Antineoplastic Agents chemistry pharmacology therapeutic use MeSH
- Pyrazines chemistry pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Bortezomib MeSH
- Ditiocarb MeSH
- Proteasome Inhibitors MeSH
- Coordination Complexes MeSH
- Boronic Acids MeSH
- Copper MeSH
- Proteasome Endopeptidase Complex MeSH
- Antineoplastic Agents MeSH
- Pyrazines MeSH
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.
References provided by Crossref.org
Diethyldithiocarbamate-copper complex ignites the tumor microenvironment through NKG2D-NKG2DL axis
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