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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals

Author(s): B. Cvek and Z. Dvorak

Volume 13 , Issue 30 , 2007

Page: [3155 - 3167] Pages: 13

DOI: 10.2174/138161207782110390

Price: $65

Abstract

Dithiocarbamates and their complexes with transition metals have been used as common pesticides, vulcanizing or analytical agents for decades. These compounds are one of the most reported inhibitors of nuclear factor-κB (NF-κB) signaling cascade. Recently, it has been found that dithiocarbamates are very potent inhibitors of proteasome. NF-κB plays a central role in the immune system and is described as a major actor in many of human cancers mainly because of its protective effects against apoptosis. Molecular mechanisms involved in regulation and function of NF-κB pathway have been elucidated recently. In particular, pivotal zinc containing proteins that alter NF-κB signal transduction were recognized. Additionally, proteasome system was found to be a key player in NF-κB pathway and is an attractive target for anticancer drug development. Collectively, the capability of dithiocarbamates to inhibit NF-κB and proteasome makes these compounds promising anticancer agents. This review focuses on the biological activity of dithiocarbamate coordination compounds with regard to their possible molecular targets in NF-κB signaling and proteasome (JAMM domain proteins). Future research should aim to find the most suitable dithiocarbamate coordination compounds for treatment of cancer and other diseases.

Keywords: Disulfiram, Diethyldithiocarbamate (DDTC), Pyrrolidinedithiocarbamate (PDTC), Metal dithiocarbamates, NF-κB, Proteasome, JAMM


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