Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.

We have characterised sites of photodamage catalysed by the cationic photosensitiser tetrabromorhodamine 123, using P388 murine leukaemia cells and a subline (P388/ADR) which has a multidrug resistance phenotype and hyperexpresses mdr1 mRNA for P-glycoprotein. Fluorescence emission spectra were cons...

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Detalles Bibliográficos
Autores principales: Kessel, D., Woodburn, K.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1995
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033570/
https://www.ncbi.nlm.nih.gov/pubmed/7841045
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author Kessel, D.
Woodburn, K.
author_facet Kessel, D.
Woodburn, K.
author_sort Kessel, D.
collection PubMed
description We have characterised sites of photodamage catalysed by the cationic photosensitiser tetrabromorhodamine 123, using P388 murine leukaemia cells and a subline (P388/ADR) which has a multidrug resistance phenotype and hyperexpresses mdr1 mRNA for P-glycoprotein. Fluorescence emission spectra were consistent with sensitiser localisation in hydrophobic regions of the P388 cell, and in more aqueous loci in P388/ADR. Subsequent irradiation resulted in photodamage to the P388 cells, resulting in loss of viability. In contrast, P388/ADR cells were unaffected except for an irreversible inhibition of P-glycoprotein, leading to enhanced accumulation of daunorubicin and rhodamine 123 and a corresponding increase in daunorubicin cytotoxicity. These results are consistent with the premise that substrates for P-glycoprotein are confined to membrane loci associated with the transporter, and indicate a very limited migration of cytotoxic photo-products in a cellular environment. IMAGES:
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spelling pubmed-20335702009-09-10 Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent. Kessel, D. Woodburn, K. Br J Cancer Research Article We have characterised sites of photodamage catalysed by the cationic photosensitiser tetrabromorhodamine 123, using P388 murine leukaemia cells and a subline (P388/ADR) which has a multidrug resistance phenotype and hyperexpresses mdr1 mRNA for P-glycoprotein. Fluorescence emission spectra were consistent with sensitiser localisation in hydrophobic regions of the P388 cell, and in more aqueous loci in P388/ADR. Subsequent irradiation resulted in photodamage to the P388 cells, resulting in loss of viability. In contrast, P388/ADR cells were unaffected except for an irreversible inhibition of P-glycoprotein, leading to enhanced accumulation of daunorubicin and rhodamine 123 and a corresponding increase in daunorubicin cytotoxicity. These results are consistent with the premise that substrates for P-glycoprotein are confined to membrane loci associated with the transporter, and indicate a very limited migration of cytotoxic photo-products in a cellular environment. IMAGES: Nature Publishing Group 1995-02 /pmc/articles/PMC2033570/ /pubmed/7841045 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
Kessel, D.
Woodburn, K.
Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.
title Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.
title_full Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.
title_fullStr Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.
title_full_unstemmed Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.
title_short Selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.
title_sort selective photodynamic inactivation of a multidrug transporter by a cationic photosensitising agent.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033570/
https://www.ncbi.nlm.nih.gov/pubmed/7841045
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