title: Phyllanthin and hypophyllanthin inhibit function of P-gp but not MRP2 in Caco-2 cells.
abstract: OBJECTIVE
  The purposes of this study were to investigate the inhibitory effects of two lignans, phyllanthin and hypophyllanthin, on the function of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2), using the in-vitro model of Caco-2 cells. In addition, the effect of prolonged exposure to these two compounds on the expression of active P-gp was also determined.
  
  
  METHODS
  The activity of P-gp and MRP2 was determined in the uptake assays by monitoring the intracellular accumulation of their specific substrates (calcein acetoxymethyl ester and 5(6)-carboxy-2',7'-dichlorofluorescein diacetate, respectively) with fluorescence spectroscopy.
  
  
  RESULTS
  Hypophyllanthin and phyllanthin inhibited P-gp function with comparable potencies, but neither compound affected MRP2 activity. When the lignans were washed out before addition of substrate, the inhibitory action of both compounds against P-gp function was lost. These results suggested the reversibility of the inhibition. Moreover, prolonged exposure of the Caco-2 cells to both lignans (up to 7 days) had no effect on P-gp function.
  
  
  CONCLUSIONS
  Phyllanthin and hypophyllanthin directly inhibited P-gp activity and did not interfere with MRP2 activity. It was likely that both phyllanthin and hypophyllanthin could reversibly inhibit P-gp function.
authors.affiliation: Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Naphassamon
authors.initials: N
authors.lastname: Sukhaphirom
authors.forename: Nontima
authors.initials: N
authors.lastname: Vardhanabhuti
authors.forename: Hemvala
authors.initials: H
authors.lastname: Chirdchupunseree
authors.forename: Pornpen
authors.initials: P
authors.lastname: Pramyothin
authors.forename: Suree
authors.initials: S
authors.lastname: Jianmongkol
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D005452:Fluoresceins / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005452:Fluoresceins; D017705:Lignans; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C053897:5(6)-carboxy-2',7'-dichlorofluorescein; C085925:calcein AM; C512682:hypophyllanthin; C517985:phyllanthin