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Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity

Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport an...

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Detalles Bibliográficos
Autores principales: da Graça Rocha, Gleice, Simões, Marisol, Oliveira, Rodrigo Rodrigues, Kaplan, Maria Auxiliadora Coelho, Gattass, Cerli Rocha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397494/
https://www.ncbi.nlm.nih.gov/pubmed/22837662
http://dx.doi.org/10.3390/ijms13066757
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author da Graça Rocha, Gleice
Simões, Marisol
Oliveira, Rodrigo Rodrigues
Kaplan, Maria Auxiliadora Coelho
Gattass, Cerli Rocha
author_facet da Graça Rocha, Gleice
Simões, Marisol
Oliveira, Rodrigo Rodrigues
Kaplan, Maria Auxiliadora Coelho
Gattass, Cerli Rocha
author_sort da Graça Rocha, Gleice
collection PubMed
description Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport and circumventing MDR, a great amount of work has been dedicated to identifying pharmacological inhibitors of specific ABC transporters. We recently showed that 3β-acetyl tormentic acid (3ATA) had no effect on P-gp/ABCB1 activity. Herein, we show that 3ATA strongly inhibited the activity of MRP1/ABCC1. In the B16/F10 and Ma104 cell lines, this effect was either 20X higher or similar to that observed with MK571, respectively. Nevertheless, the low inhibitory effect of 3ATA on A549, a cell line that expresses MRP1-5, suggests that it may not inhibit other MRPs. The use of cells transfected with ABCC2, ABCC3 or ABCC4 showed that 3ATA was also able to modulate these transporters, though with an inhibition ratio lower than that observed for MRP1/ABCC1. These data point to 3ATA as a new ABCC inhibitor and call attention to its potential use as a tool to investigate the function of MRP/ABCC proteins or as a co-adjuvant in the treatment of MDR tumors.
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spelling pubmed-33974942012-07-26 Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity da Graça Rocha, Gleice Simões, Marisol Oliveira, Rodrigo Rodrigues Kaplan, Maria Auxiliadora Coelho Gattass, Cerli Rocha Int J Mol Sci Article Multidrug resistance (MDR) is considered the main cause of cancer chemotherapy failure and patient relapse. The active drug efflux mediated by transporter proteins of the ABC (ATP-binding cassette) family is the most investigated mechanism leading to MDR. With the aim of inhibiting this transport and circumventing MDR, a great amount of work has been dedicated to identifying pharmacological inhibitors of specific ABC transporters. We recently showed that 3β-acetyl tormentic acid (3ATA) had no effect on P-gp/ABCB1 activity. Herein, we show that 3ATA strongly inhibited the activity of MRP1/ABCC1. In the B16/F10 and Ma104 cell lines, this effect was either 20X higher or similar to that observed with MK571, respectively. Nevertheless, the low inhibitory effect of 3ATA on A549, a cell line that expresses MRP1-5, suggests that it may not inhibit other MRPs. The use of cells transfected with ABCC2, ABCC3 or ABCC4 showed that 3ATA was also able to modulate these transporters, though with an inhibition ratio lower than that observed for MRP1/ABCC1. These data point to 3ATA as a new ABCC inhibitor and call attention to its potential use as a tool to investigate the function of MRP/ABCC proteins or as a co-adjuvant in the treatment of MDR tumors. Molecular Diversity Preservation International (MDPI) 2012-06-04 /pmc/articles/PMC3397494/ /pubmed/22837662 http://dx.doi.org/10.3390/ijms13066757 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
da Graça Rocha, Gleice
Simões, Marisol
Oliveira, Rodrigo Rodrigues
Kaplan, Maria Auxiliadora Coelho
Gattass, Cerli Rocha
Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity
title Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity
title_full Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity
title_fullStr Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity
title_full_unstemmed Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity
title_short Effects of 3β-Acethyl Tormentic Acid (3ATA) on ABCC Proteins Activity
title_sort effects of 3β-acethyl tormentic acid (3ata) on abcc proteins activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397494/
https://www.ncbi.nlm.nih.gov/pubmed/22837662
http://dx.doi.org/10.3390/ijms13066757
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