Table of Contents
Metal-Based Drugs
Volume 2010, Article ID 430939, 7 pages
http://dx.doi.org/10.1155/2010/430939
Review Article

Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy

1Department of Radiation Oncology, Institute of Clinical Medicine, Medical College and Hospital, National Cheng Kung University, Tainan 70428, Taiwan
2Department of Molecular Pathology, The University of Texas-MD Anderson Cancer Center, 7453 Fannin Boulevard, Houston, TX 77054, USA

Received 14 July 2010; Accepted 25 August 2010

Academic Editor: Zhe-Sheng Chen

Copyright © 2010 Helen H. W. Chen and Macus Tien Kuo. 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

Three mechanisms have been proposed for the role of glutathione (GSH) in regulating cisplatin (CDDP) sensitivities that affects its ultimate cell-killing ability: (i) GSH may serve as a cofactor in facilitating multidrug resistance protein 2- (MRP2-) mediated CDDP efflux in mammalian cells, since MRP2-transfected cells were shown to confer CDDP resistance; (ii) GSH may serve as a redox-regulating cytoprotector based on the observations that many CDDP-resistant cells overexpress GSH and γ-glutamylcysteine synthesis (γ-GCS), the rate-limiting enzyme for GSH biosynthesis; (iii) GSH may function as a copper (Cu) chelator. Elevated GSH expression depletes the cellular bioavailable Cu pool, resulting in upregulation of the high-affinity Cu transporter (hCtr1) which is also a CDDP transporter. This has been demonstrated that overexpression of GSH by transfection with γ-GCS conferred sensitization to CDDP toxicity. This review describes how these three models were developed and critically reviews their importance to overall CDDP cytotoxicity in cancer cell treatments.