title: Resveratrol oligomers are potent MRP1 transport inhibitors.
abstract: 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.
authors.affiliation: Department of Biology, Abo Akademi University, FIN-20520 Abo/Turku, Finland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bobrowska-Hägerstrand
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lillås
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mrówczyñska
authors.forename: Anna
authors.initials: A
authors.lastname: Wróbel
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shirataki
authors.forename: Noboru
authors.initials: N
authors.lastname: Motohashi
authors.forename: Henry
authors.initials: H
authors.lastname: Hägerstrand
mesh_terms: 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*
chemical_list: C473073:2',7'-bis-(carboxypropyl)-5(6)-carboxyfluorescein; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005452:Fluoresceins; D013267:Stilbenes; D000077185:Resveratrol