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Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.

Resistance to chemotherapy is a major problem in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). Important factors involved are drug detoxification by glutathione (GSH) and reduced drug accumulation due to active transport out of the cell by so-called 'multidrug re...

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Autores principales: Welters, M. J., Fichtinger-Schepman, A. M., Baan, R. A., Flens, M. J., Scheper, R. J., Braakhuis, B. J.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149938/
https://www.ncbi.nlm.nih.gov/pubmed/9484811
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author Welters, M. J.
Fichtinger-Schepman, A. M.
Baan, R. A.
Flens, M. J.
Scheper, R. J.
Braakhuis, B. J.
author_facet Welters, M. J.
Fichtinger-Schepman, A. M.
Baan, R. A.
Flens, M. J.
Scheper, R. J.
Braakhuis, B. J.
author_sort Welters, M. J.
collection PubMed
description Resistance to chemotherapy is a major problem in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). Important factors involved are drug detoxification by glutathione (GSH) and reduced drug accumulation due to active transport out of the cell by so-called 'multidrug resistance-related proteins'. We have studied a panel of eight HNSCC cell lines showing differences in sensitivity to the anti-cancer drug cisplatin. Our previous studies indicated that the IC50 values were inversely correlated with the intracellular accumulation of platinum (Pt). In the present study, cellular GSH levels were found not to be related to the IC50 values. The expression levels of the enzymes glutathione S-transferase (GST) alpha, mu, and pi, the multidrug resistance-related proteins P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and the lung resistance protein (LRP) were determined semiquantitatively by means of immunocytochemistry. The levels of the GSTs, P-gp and LRP were not found to be correlated with the IC50 values of the HNSCC cell lines. Surprisingly, however, an inverse correlation was found between MRP levels and IC50 values. The MRP expression levels were in agreement with the results of the MRP functional assay, based on the transport of calcein across the cell membrane as performed for two of the cell lines. Further studies should prove whether other pump mechanisms or DNA repair are involved in the cisplatin accumulation and the subsequent HNSCC cell growth inhibition.
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spelling pubmed-21499382009-09-10 Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines. Welters, M. J. Fichtinger-Schepman, A. M. Baan, R. A. Flens, M. J. Scheper, R. J. Braakhuis, B. J. Br J Cancer Research Article Resistance to chemotherapy is a major problem in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). Important factors involved are drug detoxification by glutathione (GSH) and reduced drug accumulation due to active transport out of the cell by so-called 'multidrug resistance-related proteins'. We have studied a panel of eight HNSCC cell lines showing differences in sensitivity to the anti-cancer drug cisplatin. Our previous studies indicated that the IC50 values were inversely correlated with the intracellular accumulation of platinum (Pt). In the present study, cellular GSH levels were found not to be related to the IC50 values. The expression levels of the enzymes glutathione S-transferase (GST) alpha, mu, and pi, the multidrug resistance-related proteins P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and the lung resistance protein (LRP) were determined semiquantitatively by means of immunocytochemistry. The levels of the GSTs, P-gp and LRP were not found to be correlated with the IC50 values of the HNSCC cell lines. Surprisingly, however, an inverse correlation was found between MRP levels and IC50 values. The MRP expression levels were in agreement with the results of the MRP functional assay, based on the transport of calcein across the cell membrane as performed for two of the cell lines. Further studies should prove whether other pump mechanisms or DNA repair are involved in the cisplatin accumulation and the subsequent HNSCC cell growth inhibition. Nature Publishing Group 1998-02 /pmc/articles/PMC2149938/ /pubmed/9484811 Text en 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 Research Article
Welters, M. J.
Fichtinger-Schepman, A. M.
Baan, R. A.
Flens, M. J.
Scheper, R. J.
Braakhuis, B. J.
Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.
title Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.
title_full Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.
title_fullStr Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.
title_full_unstemmed Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.
title_short Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.
title_sort role of glutathione, glutathione s-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2149938/
https://www.ncbi.nlm.nih.gov/pubmed/9484811
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