The multidrug resistance protein family

Borst, Piet; Evers, Raymond; Kool, Marcel; Wijnholds, Jan

doi:10.1016/s0005-2736(99)00167-4

Cited by 594 publications

(452 citation statements)

References 36 publications

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“…Multidrug-resistance associated proteins (MRPs) belong to the subfamily C of ATP binding cassette (ABC) superfamily, which are characterized by the ATP-dependent export of lipophilic substances conjugated to glutathione, glucuronate, or sulfate (Borst et al, 1999). The name of MRPs comes from their potential roles in clinical multidrug resistance, as overexpression of MRP transporters in tumor cells often leads to decreased cellular drug accumulation and represents a major obstacle to the treatment of disseminated cancers (Hagmann et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals

Long

Zhong

et al. 2011

Comparative Biochemistry and Physiology Part C: Toxicology &

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Section: Introductionmentioning

confidence: 99%

Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals

Long

Zhong

et al. 2011

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…The ATP-binding cassette transporter (ABC) superfamily has been implicated as a major contributor to the multidrugresistance phenotype (Klein et al, 1999). The most studied members are the P-glycoprotein (P-gp) encoded by the MDR1 gene (Ambudkar et al, 1999) and the MDR-related protein (MRP) family of the ABC protein transporters, especially the MRP1 gene (Borst et al, 1999). Currently, 48 human ABC transporters are known (Müller M (2001).…”

mentioning

confidence: 99%

Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation

Boonstra¹,

Timmer‐Bosscha

Echten-Arends

et al. 2004

Br J Cancer

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The aim of this study was to find factors that could explain the accumulation difference of mitoxantrone in the BCRP1-negative GLC4-MITO cell line compared to GLC4. Comparative genomic hybridisation (CGH) was applied to determine chromosomal differences between GLC4 and GLC4-MITO. Comparative genomic hybridisation analysis revealed gain of 2q, 6p, 9q, 13q, 14q, 15q, 19q and Xp and loss of 1p, 2q, 3p, 3q, 4q, 6q, 8q, 11p, 16p, 17q, 18p, 20p and Xq. In the over-represented chromosomal areas, seven transporter genes were identified: ABCB6, ABCB2 (TAP1), ABCB3 (TAP2), ABCF1 (ABC50), ABCC10 (MRP7), ABCA2 (ABC2) and ABCC4 (MRP4). No RNA or protein upregulation was observed for ABCB6, ABCF1, ABCC10, ABCC4, ABCB2 and ABCB3, but an increased expression was detected for ABCA2 mRNA in GLC4-MITO. ABCA2 is known to be involved in resistance to estramustine. In the MTT assay, GLC4-MITO was two-fold resistant to estramustine compared to GLC4. Coincubation with estramustine and mitoxantrone increased mitoxantrone accumulation in GLC4-MITO, while this was not affected in GLC4. This suggests that estramustine is able to block mitoxantrone efflux in GLC4-MITO cells. These data reveal that cellular reduction of mitoxantrone in a mitoxantrone-resistant cell line is associated with overexpression of ABCA2.

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“…Otra estrategia consiste en la utilización de medicamentos que no sean afines a las Pgp, tales como la ciclofosfamida y el cis-platino aunque son pocos los medicamentos disponibles con estas propiedades y no se lograría inhibir el transporte de algunos compuestos análogos (35).…”

Section: Posibles Estrategias Para Revertir El Fenotipo Mdrunclassified

Leishmania: papel de la glicoproteína P en la mediación de resistencia a medicamentos y estrategias de reversión.

et al. 2005

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Actualmente, los parásitos protozoarios son uno de los principales agentes causantes de morbilidad y mortalidad en el mundo, un problema complicado, además, por la aparición de resistencia a medicamentos en estos organismos. La resistencia a medicamentos observada en parásitos protozoarios se debe a diferentes mecanismos como la disminución de la entrada del medicamento a la célula por cambios en el transportador requerido, la pérdida de la activación del medicamento por parte del hospedero, las alteraciones en el blanco del medicamento y la expresión exagerada del transportador múltiple de medicamentos o glicoproteína P (Pgp). En esta revisión, nos centramos en: 1) el papel de las glicoproteínas P (Pgp) de la familia de proteínas ABC (ATP binding cassette) como los transportadores de múltiples medicamentos en la mediación de resistencia en protozoarios, especialmente en Leishmania, y en el desarrollo de resistencia cruzada para medicamentos estructural y funcionalmente no relacionados, y 2) en algunos conceptos relacionados con los mecanismos moduladores que podrían revertir la resistencia a medicamentos por fármacos y productos naturales. Numerosos moduladores o quimiosensibilizadores son conocidos por alterar la capacidad de las glicoproteínas P para mantener concentraciones intracelulares subtóxicas del medicamento; algunos ejemplos incluyen los bloqueadores de los canales de calcio como el verapamilo; sin embargo, se requieren altas concentraciones para una inhibición eficiente y duradera, las cuales producen efectos adversos indeseables. Por tanto, se necesitan más investigaciones relacionadas con los moduladores naturales para Pgp, los cuales podrían presentar menor toxicidad para el hospedero.Palabras clave: Leishmania, protozoos, multirresistencia, glicoproteína P, productos naturales. Leishmania: role of P glycoprotein in drug resistance and reversion strategiesProtozoan parasites are important causative agents of morbidity and mortality throughout the world -a problem further complicated by the emergence of drug resistance in these parasites. Mechanisms of drug resistance include the following: decreased uptake of the drug into the cell, loss of drug activation, alterations in the drug target, and over-expression of a well-known multiple drug transporter proteins. In this review, two critical components of resistance are stressed: (1) the role of ATP binding cassette proteins, such as P-glycoproteins, in mediating drug resistance in Leishmania and other protozoans, followed by development of cross-resistance to many structurally and functionally unrelated drugs, and (2) some concepts concerning the reversal mechanism of multidrug resistance by drugs and natural products. Several modulators or chemosensitizers alter the capacity of P-glycoproteins to maintain subtoxic intracellular drug concentrations. Calcium channel blockers such as verapamil act in this mode; however, high concentrations are required for an efficient and effective inhibition and, in addition, produce undesirable side effects. The di...

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The multidrug resistance protein family

Cited by 594 publications

References 36 publications

Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals

Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals

Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation

Leishmania: papel de la glicoproteína P en la mediación de resistencia a medicamentos y estrategias de reversión.

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