Interaction of the breast cancer resistance protein with plant polyphenols.
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.
Cooray
Hiran C
HC
Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
Janvilisri
Tavan
T
van Veen
Hendrik W
HW
Hladky
Stephen B
SB
Barrand
Margery A
MA
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001896:Boron Compounds / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D013294:Lactococcus lactis / Q000166:cytology; D008942:Mitoxantrone / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D010944:Plants / Q000737:chemistry*; D059808:Polyphenols; D011224:Prazosin / Q000031:analogs & derivatives* / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C412306:BODIPY-FL prazosin; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009363:Neoplasm Proteins; D010636:Phenols; D059808:Polyphenols; D014638:Vanadates; D008942:Mitoxantrone; D000251:Adenosine Triphosphatases; D011224:Prazosin