Resveratrol oligomers are potent MRP1 transport inhibitors
Bobrowska-Hägerstrand, M.; Lillås, M.; Mrówczyñska, L.; Wróbel, A.; Shirataki, Y.; Motohashi, N.; Hägerstrand, H.
Anticancer Research 26(3a): 2081-2084
2006
ISSN/ISBN: 0250-7005 PMID: 16827148 Document Number: 600740
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. Materials and 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 micro M) > sophorastilbene A (IC50=3.1 micro M) > (minus)- epsilon -viniferin (IC50=8.9 micro M) > piceatannol (IC50=57 micro M). Resveratrol and rhaponticin were ineffective. (+)- alpha -Viniferin (IC50=0.8 micro M), sophorastilbene A (IC50=3.7 micro M) and (-)- epsilon -viniferin (IC50=3.5 micro M) were also efficient BCPCF transport inhibitors in IOVs. Conclusion: 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.