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Combined effects of GSTP1 and MRP1 in melanoma drug resistance
Glutathione-S-transferase Pi1 (GSTP1) and multidrug resistance protein 1 (MRP1) are overexpressed in melanoma, a skin cancer notoriously resistant to all current modalities of cancer therapy. To investigate the involvement of these detoxifying enzymes in the drug resistance of melanoma, an inducible...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2005
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361556/ https://www.ncbi.nlm.nih.gov/pubmed/15999103 http://dx.doi.org/10.1038/sj.bjc.6602681 |
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author | Depeille, P Cuq, P Passagne, I Evrard, A Vian, L |
author_facet | Depeille, P Cuq, P Passagne, I Evrard, A Vian, L |
author_sort | Depeille, P |
collection | PubMed |
description | Glutathione-S-transferase Pi1 (GSTP1) and multidrug resistance protein 1 (MRP1) are overexpressed in melanoma, a skin cancer notoriously resistant to all current modalities of cancer therapy. To investigate the involvement of these detoxifying enzymes in the drug resistance of melanoma, an inducible (Tet-On™ system) antisense (AS) RNA strategy was used to specifically inhibit GSTP1 expression in A375 cells, a human melanoma cell line expressing high levels of GSTP1 and MRP1. Stable transfectant clones were established and analysed for GSTP1 inhibition by AS RNA. The clone A375-ASPi1, presenting a specific 40% inhibition of GSTP1 expression in the presence of doxycycline, was selected. Lowering the GSTP1 level significantly increased (about 3.3-fold) the sensitivity of A375-ASPi1 cells to etoposide. Inhibitors of glutathione synthesis (BSO), GSTs (curcumin, ethacrynic acid), and also of MRPs (MK571, sulphinpyrazone) improved the sensitising effect of GSTP1 AS RNA. All these inhibitors had stronger sensitising effects in control cells expressing high GSTP1 level (A375-ASPi1 cells in the absence of doxycycline). In conclusion, GSTP1 can act in a combined fashion with MRP1 to protect melanoma cells from toxic effects of etoposide. |
format | Text |
id | pubmed-2361556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23615562009-09-10 Combined effects of GSTP1 and MRP1 in melanoma drug resistance Depeille, P Cuq, P Passagne, I Evrard, A Vian, L Br J Cancer Translational Therapeutics Glutathione-S-transferase Pi1 (GSTP1) and multidrug resistance protein 1 (MRP1) are overexpressed in melanoma, a skin cancer notoriously resistant to all current modalities of cancer therapy. To investigate the involvement of these detoxifying enzymes in the drug resistance of melanoma, an inducible (Tet-On™ system) antisense (AS) RNA strategy was used to specifically inhibit GSTP1 expression in A375 cells, a human melanoma cell line expressing high levels of GSTP1 and MRP1. Stable transfectant clones were established and analysed for GSTP1 inhibition by AS RNA. The clone A375-ASPi1, presenting a specific 40% inhibition of GSTP1 expression in the presence of doxycycline, was selected. Lowering the GSTP1 level significantly increased (about 3.3-fold) the sensitivity of A375-ASPi1 cells to etoposide. Inhibitors of glutathione synthesis (BSO), GSTs (curcumin, ethacrynic acid), and also of MRPs (MK571, sulphinpyrazone) improved the sensitising effect of GSTP1 AS RNA. All these inhibitors had stronger sensitising effects in control cells expressing high GSTP1 level (A375-ASPi1 cells in the absence of doxycycline). In conclusion, GSTP1 can act in a combined fashion with MRP1 to protect melanoma cells from toxic effects of etoposide. Nature Publishing Group 2005-07-25 2005-07-05 /pmc/articles/PMC2361556/ /pubmed/15999103 http://dx.doi.org/10.1038/sj.bjc.6602681 Text en Copyright © 2005 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Translational Therapeutics Depeille, P Cuq, P Passagne, I Evrard, A Vian, L Combined effects of GSTP1 and MRP1 in melanoma drug resistance |
title | Combined effects of GSTP1 and MRP1 in melanoma drug resistance |
title_full | Combined effects of GSTP1 and MRP1 in melanoma drug resistance |
title_fullStr | Combined effects of GSTP1 and MRP1 in melanoma drug resistance |
title_full_unstemmed | Combined effects of GSTP1 and MRP1 in melanoma drug resistance |
title_short | Combined effects of GSTP1 and MRP1 in melanoma drug resistance |
title_sort | combined effects of gstp1 and mrp1 in melanoma drug resistance |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361556/ https://www.ncbi.nlm.nih.gov/pubmed/15999103 http://dx.doi.org/10.1038/sj.bjc.6602681 |
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