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

• Autorzy: Wesolowska O , Hendrich A.B. , Lania-Pietrzak B. , Wisniewski J. , Molnar J. , Ocsovszki I. , Michalak K.
• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

perturbation; lipid phase; membrane; modulation; multidrug resistance-associated protein 1; flavonoids; lipid bilayer; carbocyanine dye

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2009
• Tom: 14
• Numer: 2
• Opis fizyczny: p.199-221,fig.,ref.

Twórcy

autor

Wesolowska O

• Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland

autor

Hendrich A.B.

autor

Lania-Pietrzak B.

autor

Wisniewski J.

autor

Molnar J.

autor

Ocsovszki I.

autor

Michalak K.

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