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Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters
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....
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Formato: | Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025362/ https://www.ncbi.nlm.nih.gov/pubmed/21274436 http://dx.doi.org/10.1155/2010/317581 |
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author | Abada, Paolo Howell, Stephen B. |
author_facet | Abada, Paolo Howell, Stephen B. |
author_sort | Abada, Paolo |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3025362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-30253622011-01-27 Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters Abada, Paolo Howell, Stephen B. Met Based Drugs Review Article 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. Hindawi Publishing Corporation 2010 2011-01-09 /pmc/articles/PMC3025362/ /pubmed/21274436 http://dx.doi.org/10.1155/2010/317581 Text en Copyright © 2010 P. Abada and S. B. Howell. 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 Abada, Paolo Howell, Stephen B. Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters |
title | Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters |
title_full | Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters |
title_fullStr | Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters |
title_full_unstemmed | Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters |
title_short | Regulation of Cisplatin Cytotoxicity by Cu Influx Transporters |
title_sort | regulation of cisplatin cytotoxicity by cu influx transporters |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025362/ https://www.ncbi.nlm.nih.gov/pubmed/21274436 http://dx.doi.org/10.1155/2010/317581 |
work_keys_str_mv | AT abadapaolo regulationofcisplatincytotoxicitybycuinfluxtransporters AT howellstephenb regulationofcisplatincytotoxicitybycuinfluxtransporters |