Interaction of the breast cancer resistance protein with plant polyphenols.

Hiran C Cooray, Tavan Janvilisri, Hendrik W van Veen, Stephen B Hladky, Margery A Barrand

Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.

Biochemical and biophysical research communications 2004 Apr 23

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Multidrug transporters influence drug distribution in vivo and are often associated with tumour drug resistance. Here we show that plant-derived polyphenols that interact with P-glycoprotein can also modulate the activity of the recently discovered ABC transporter, breast cancer resistance protein (BCRP/ABCG2). In two separate BCRP-overexpressing cell lines, accumulation of the established BCRP substrates mitoxantrone and bodipy-FL-prazosin was significantly increased by the flavonoids silymarin, hesperetin, quercetin, and daidzein, and the stilbene resveratrol (each at 30 microM) as measured by flow cytometry, though there was no corresponding increase in the respective wild-type cell lines. These compounds also stimulated the vanadate-inhibitable ATPase activity in membranes prepared from bacteria (Lactococcus lactis) expressing BCRP. Given the high dietary intake of polyphenols, such interactions with BCRP, particularly in the intestines, may have important consequences in vivo for the distribution of these compounds as well as other BCRP substrates.

Citation

Hiran C Cooray, Tavan Janvilisri, Hendrik W van Veen, Stephen B Hladky, Margery A Barrand. Interaction of the breast cancer resistance protein with plant polyphenols. Biochemical and biophysical research communications. 2004 Apr 23;317(1):269-75