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Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins

Most of the substances used as fluorescent probes to study drug transport and the effect of efflux blockers in multidrug resistant cells have many drawbacks, such as toxicity, unspecific background, accumulation in mitochondria. New fluorescent compounds, among which Bodipy‐FL‐verapamil (BV), have b...

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Autores principales: Rosati, Anna, Candussio, Luigi, Crivellato, Enrico, Klugmann, Fiora Bartoli, Giraldi, Tullio, Damiani, Daniela, Michelutti, Angela, Decorti, Giuliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611116/
https://www.ncbi.nlm.nih.gov/pubmed/15371652
http://dx.doi.org/10.1155/2004/576173
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author Rosati, Anna
Candussio, Luigi
Crivellato, Enrico
Klugmann, Fiora Bartoli
Giraldi, Tullio
Damiani, Daniela
Michelutti, Angela
Decorti, Giuliana
author_facet Rosati, Anna
Candussio, Luigi
Crivellato, Enrico
Klugmann, Fiora Bartoli
Giraldi, Tullio
Damiani, Daniela
Michelutti, Angela
Decorti, Giuliana
author_sort Rosati, Anna
collection PubMed
description Most of the substances used as fluorescent probes to study drug transport and the effect of efflux blockers in multidrug resistant cells have many drawbacks, such as toxicity, unspecific background, accumulation in mitochondria. New fluorescent compounds, among which Bodipy‐FL‐verapamil (BV), have been therefore proposed as more useful tools. The uptake of BV has been evaluated by cytofluorimetry and fluorescence microscopy using cell lines that overexpress P‐glycoprotein (P388/ADR and LLC‐PK1/ADR) or MRP (multidrug resistance‐related protein) (PANC‐1) and clinical specimens from patients. The effect of specific inhibitors for P‐glycoprotein (verapamil and vinblastine) or MRP (MK571 and probenecid) has been also studied. BV intracellular concentrations were significantly lower in the two P‐glycoprotein overexpressing cell lines in comparison with the parental lines. In addition, verapamil and vinblastine increased the intracellular concentrations of the dye; MK571 and probenecid, two MRP inhibitors, increased BV levels in PANC‐1 cells, that express this protein. These findings were confirmed in clinical specimens from patients. Fluorescence microscopy revealed a faint fluorescence emission in P‐glycoprotein or MRP expressing cell lines; however, treatment with specific inhibitors significantly increased the fluorescence. BV is a useful tool for studying multidrug resistance proteins with different techniques such as cytofluorimetry and fluorescence microscopy, but does not discriminate between P‐glycoprotein and MRP. In comparison with other classic fluorescent probes, the assay with this dye is extremely rapid, simple, not toxic for cells, devoid of fluorescent background, and can be useful in the clinical settings.
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spelling pubmed-46111162016-01-12 Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins Rosati, Anna Candussio, Luigi Crivellato, Enrico Klugmann, Fiora Bartoli Giraldi, Tullio Damiani, Daniela Michelutti, Angela Decorti, Giuliana Cell Oncol Other Most of the substances used as fluorescent probes to study drug transport and the effect of efflux blockers in multidrug resistant cells have many drawbacks, such as toxicity, unspecific background, accumulation in mitochondria. New fluorescent compounds, among which Bodipy‐FL‐verapamil (BV), have been therefore proposed as more useful tools. The uptake of BV has been evaluated by cytofluorimetry and fluorescence microscopy using cell lines that overexpress P‐glycoprotein (P388/ADR and LLC‐PK1/ADR) or MRP (multidrug resistance‐related protein) (PANC‐1) and clinical specimens from patients. The effect of specific inhibitors for P‐glycoprotein (verapamil and vinblastine) or MRP (MK571 and probenecid) has been also studied. BV intracellular concentrations were significantly lower in the two P‐glycoprotein overexpressing cell lines in comparison with the parental lines. In addition, verapamil and vinblastine increased the intracellular concentrations of the dye; MK571 and probenecid, two MRP inhibitors, increased BV levels in PANC‐1 cells, that express this protein. These findings were confirmed in clinical specimens from patients. Fluorescence microscopy revealed a faint fluorescence emission in P‐glycoprotein or MRP expressing cell lines; however, treatment with specific inhibitors significantly increased the fluorescence. BV is a useful tool for studying multidrug resistance proteins with different techniques such as cytofluorimetry and fluorescence microscopy, but does not discriminate between P‐glycoprotein and MRP. In comparison with other classic fluorescent probes, the assay with this dye is extremely rapid, simple, not toxic for cells, devoid of fluorescent background, and can be useful in the clinical settings. IOS Press 2004 2004-07-14 /pmc/articles/PMC4611116/ /pubmed/15371652 http://dx.doi.org/10.1155/2004/576173 Text en Copyright © 2004 Hindawi Publishing Corporation and the authors.
spellingShingle Other
Rosati, Anna
Candussio, Luigi
Crivellato, Enrico
Klugmann, Fiora Bartoli
Giraldi, Tullio
Damiani, Daniela
Michelutti, Angela
Decorti, Giuliana
Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins
title Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins
title_full Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins
title_fullStr Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins
title_full_unstemmed Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins
title_short Bodipy-FL-Verapamil: A Fluorescent Probe for the Study of Multidrug Resistance Proteins
title_sort bodipy-fl-verapamil: a fluorescent probe for the study of multidrug resistance proteins
topic Other
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611116/
https://www.ncbi.nlm.nih.gov/pubmed/15371652
http://dx.doi.org/10.1155/2004/576173
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