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

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 MR...

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Detalles Bibliográficos
Autores principales: Chen, Helen H. W., Kuo, Macus Tien
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946579/
https://www.ncbi.nlm.nih.gov/pubmed/20885916
http://dx.doi.org/10.1155/2010/430939
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author Chen, Helen H. W.
Kuo, Macus Tien
author_facet Chen, Helen H. W.
Kuo, Macus Tien
author_sort Chen, Helen H. W.
collection PubMed
description 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.
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spelling pubmed-29465792010-09-30 Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy Chen, Helen H. W. Kuo, Macus Tien Met Based Drugs Review Article 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. Hindawi Publishing Corporation 2010 2010-09-14 /pmc/articles/PMC2946579/ /pubmed/20885916 http://dx.doi.org/10.1155/2010/430939 Text en Copyright © 2010 H. H. W. Chen and M. T. Kuo. https://creativecommons.org/licenses/by/3.0/ 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.
spellingShingle Review Article
Chen, Helen H. W.
Kuo, Macus Tien
Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy
title Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy
title_full Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy
title_fullStr Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy
title_full_unstemmed Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy
title_short Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy
title_sort role of glutathione in the regulation of cisplatin resistance in cancer chemotherapy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946579/
https://www.ncbi.nlm.nih.gov/pubmed/20885916
http://dx.doi.org/10.1155/2010/430939
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