Resveratrol oligomers are potent MRP1 transport inhibitors.
BACKGROUND
Knowledge of the structure-activity relationships of multidrug resistance protein 1 (MRP1, ABCC1) inhibitors may aid in developing potent inhibitors that can be used to circumvent MRP1-mediated multidrug resistance.


METHODS
Six stilbenes were examined for their ability to inhibit MRP1-mediated transport of 2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein (BCPCF) from human erythrocytes and into inside-out erythrocyte membrane vesicles (IOVs). The concentrations of stilbenes decreasing BCPCF transport by 50% during 60 min of incubation at 37 degrees C (IC50) were determined from dose-response curves.


RESULTS
Stilbenes inhibited BCPCF transport in cells in the rank order (+)-alpha-viniferin (IC50 = 0.8 microM) > sophorastilbene A (IC50 = 3.1 microM) > (-)-epsilon-viniferin (IC50 = 8.9 microM) > piceatannol (IC50 = 57 microM). Resveratrol and rhaponticin were ineffective. (+)-alpha-Viniferin (IC50 = 0.8 microM), sophorastilbene A (IC50 = 3.7 microM) and (-)-epsilon-viniferin (IC50 = 3.5 microM) were also efficient BCPCF transport inhibitors in IOVs.


CONCLUSIONS
Stilbenes may efficiently inhibit MRP1-mediated organic anion transport. This inhibitory potency of stilbenes increases with oligomerisation. The membrane is not a strong barrier for the inhibitory activity of the trimeric stilbenes.
Bobrowska-Hägerstrand
Malgorzata
M
Department of Biology, Abo Akademi University, FIN-20520 Abo/Turku, Finland.
Lillås
Magdalena
M
Mrówczyñska
Lucyna
L
Wróbel
Anna
A
Shirataki
Yoshiaki
Y
Motohashi
Noboru
N
Hägerstrand
Henry
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005452:Fluoresceins / Q000493:pharmacokinetics; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
C473073:2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005452:Fluoresceins; D013267:Stilbenes; D000077185:Resveratrol