Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein

Szabolcs Tarapcsák, Gábor Szalóki, Ágnes Telbisz, Zsuzsanna Gyöngy, Krisztina Matúz, Éva Csosz, Péter Nagy, Imre J. Holb, Ralph Rühl, L. Nagy, Gábor Szabó, K. Goda

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Abstract

Retinoids - derivatives of vitamin A - are important cell permeant signaling molecules that regulate gene expression through activation of nuclear receptors. P-glycoprotein (Pgp) and ABCG2 are plasma membrane efflux transporters affecting the tissue distribution of numerous structurally unrelated lipophilic compounds. In the present work we aimed to study the interaction of the above ABC transporters with retinoid derivatives. We have found that 13-cis-retinoic acid, retinol and retinyl-acetate inhibited the Pgp and ABCG2 mediated substrate transport as well as the substrate stimulated ATPase activity of these transporters. Interestingly, 9-cis-retinoic acid and ATRA (all-trans retinoic acid), both are stereoisomers of 13-cis-retinoic acid, did not have any effect on the transporters' activity. Our fluorescence anisotropy measurements revealed that 13-cis-retinoic acid, retinol and retinyl-acetate selectively increase the viscosity and packing density of the membrane. Thus, the mixed-type inhibition of both transporters by retinol and ABCG2 by 13-cis-retinoic acid may be the collective result of direct interactions of these retinoids with the substrate binding site(s) and of indirect interactions mediated by their membrane rigidifying effects.

Original languageEnglish
Article number41376
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Feb 1 2017

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Isotretinoin
ATP-Binding Cassette Transporters
Retinoids
P-Glycoprotein
Breast Neoplasms
Vitamin A
Proteins
Stereoisomerism
Fluorescence Polarization
Membranes
Membrane Transport Proteins
Tissue Distribution
Cytoplasmic and Nuclear Receptors
Tretinoin
Viscosity
Adenosine Triphosphatases
Binding Sites
Cell Membrane
Gene Expression
retinol acetate

ASJC Scopus subject areas

  • General

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Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein. / Tarapcsák, Szabolcs; Szalóki, Gábor; Telbisz, Ágnes; Gyöngy, Zsuzsanna; Matúz, Krisztina; Csosz, Éva; Nagy, Péter; Holb, Imre J.; Rühl, Ralph; Nagy, L.; Szabó, Gábor; Goda, K.

In: Scientific Reports, Vol. 7, 41376, 01.02.2017.

Research output: Contribution to journalArticle

Tarapcsák, S, Szalóki, G, Telbisz, Á, Gyöngy, Z, Matúz, K, Csosz, É, Nagy, P, Holb, IJ, Rühl, R, Nagy, L, Szabó, G & Goda, K 2017, 'Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein', Scientific Reports, vol. 7, 41376. https://doi.org/10.1038/srep41376
Tarapcsák, Szabolcs ; Szalóki, Gábor ; Telbisz, Ágnes ; Gyöngy, Zsuzsanna ; Matúz, Krisztina ; Csosz, Éva ; Nagy, Péter ; Holb, Imre J. ; Rühl, Ralph ; Nagy, L. ; Szabó, Gábor ; Goda, K. / Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein. In: Scientific Reports. 2017 ; Vol. 7.
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