Table of Contents
Metal-Based Drugs
Volume 2010 (2010), Article ID 317581, 9 pages
http://dx.doi.org/10.1155/2010/317581
Review Article

Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters

Moores Cancer Center and Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA

Received 9 August 2010; Accepted 7 December 2010

Academic Editor: Giovanni Natile

Copyright © 2010 Paolo Abada and Stephen B. Howell. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Platinum drugs are an important class of cancer chemotherapeutics. However, the use of these drugs is limited by the development of resistance during treatment with decreased accumulation being a common mechanism. Both Cu transporters CTR1 and CTR2 influence the uptake and cytotoxicity of cisplatin. Although it is structurally similar to CTR1, CTR2 functions in a manner opposite to that of CTR1 with respect to Pt drug uptake. Whereas knockout of CTR1 reduces Pt drug uptake, knockdown of CTR2 enhances cisplatin uptake and cytotoxicity. CTR2 is subject to transcriptional and posttranscriptional regulation by both Cu and cisplatin; this regulation is partly dependent on the Cu chaperone ATOX1. Insight into the mechanisms by which CTR1 and CTR2 regulate sensitivity to the Pt-containing drugs has served as the basis for novel pharmacologic strategies for improving their efficacy.