Perturbation of the lipid phase of a membrane is not involved in the modulation of MRP1 transport activity by flavonoids

Cellular & Molecular Biology Letters

Jerzy Wiśniewski³  Krystyna Michalak³  Andrzej B. Hendrich³  Joseph Molnar²  Imre Ocsovszki¹  Barbara Łania-Pietrzak³  Olga Wesołowska³ 

[1] Department of Biochemistry, University of Szeged, Szeged, Hungary$$;Institute of Medical Microbiology, University of Szeged, Szeged, Hungary$$;Department of Biophysics, Wrocław Medical University, Wrocław, Poland$$

关键词: Flavonoids;    Multidrug resistance-associated protein 1 (MRP1);    Lipid bilayer;    Carbocyanine dyes;   

DOI  :  10.2478/s11658-008-0044-3

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

The expression of transmembrane transporter multidrug resistance-associated protein 1 (MRP1) confers the multidrug-resistant phenotype (MDR) on cancer cells. Since the activity of the other MDR transporter, P-glycoprotein, is sensitive to membrane perturbation, we aimed to check whether the changes in lipid bilayer properties induced by flavones (apigenin, acacetin) and flavonols (morin, myricetin) were related to their MRP1 inhibitory activity. All the flavonoids inhibited the efflux of MRP1 fluorescent substrate from human erythrocytes and breast cancer cells. Morin was also found to stimulate the ATPase activity of erythrocyte ghosts. All flavonoids intercalated into phosphatidylcholine bilayers as judged by differential scanning calorimetry and fluorescence spectroscopy with the use of two carbocyanine dyes. The model of an intramembrane localization for flavones and flavonols was proposed. No clear relationship was found between the membrane-perturbing activity of flavonoids and their potency to inhibit MRP1. We concluded that mechanisms other than perturbation of the lipid phase of membranes were responsible for inhibition of MRP1 by the flavonoids.

【 授权许可】

Unknown