Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in caco-2 cells

Biol Pharm Bull. 1998 Oct;21(10):1062-6. doi: 10.1248/bpb.21.1062.


We investigated the effect of components in grapefruit juice (GFJ) on the transport of vinblastine, a substrate of P-glycoprotein (P-gp), across Caco-2 cells. The apical to basolateral flux of [3H]vinblastine was increased in the presence of GFJ extracts. The steady-state uptake of [3H]vinblastine from the apical side was significantly increased in the presence of GFJ in a dose-dependent manner within the range of 2.5 to 50% (v/v) of GFJ. Although naringin and naringenin reduced apical efflux of [3H]vinblastine at the concentration present in GFJ and increased steady-state uptake from the apical side to 124 and 240%, respectively, the observed effect of naringin was not enough to account for the effect of GFJ and naringenin is not naturally present in GFJ. To investigate the effective components in GFJ, we examined the inhibitory effect of several organic solvent extracts of GFJ on the transport of [3H]vinblastine in Caco-2 cells. Organic solvent extracts of GFJ enhanced the apical to basolateral transcellular transport and inhibited the apical efflux. The permeability coefficient of apical to basolateral transport of [3H]vinblastine increased in the order of the ethyl acetate>diethyl ether>methylene chloride extracts of GFJ. Since the extracted amount of naringenin by ethyl acetate was less than that with the other organic solvents, the primary inhibitor in GFJ is suggested to be different from this flavonoid. The present study demonstrated the existence of inhibitory components in GFJ for the P-gp function in Caco-2 cells, which are distinct from known components such as naringin or naringenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antioxidants / pharmacology
  • Beverages*
  • Biological Transport / drug effects
  • Caco-2 Cells / drug effects*
  • Caco-2 Cells / enzymology
  • Caco-2 Cells / metabolism*
  • Cell Survival / drug effects
  • Citrus*
  • Cyclosporine / pharmacology
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Estrogen Antagonists / pharmacology
  • Flavanones*
  • Flavonoids / pharmacology
  • Food-Drug Interactions
  • Humans
  • Intestinal Absorption / drug effects
  • Mixed Function Oxygenases / metabolism
  • Plant Extracts / pharmacology*
  • Tritium
  • Vinblastine / pharmacokinetics*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Enzyme Inhibitors
  • Estrogen Antagonists
  • Flavanones
  • Flavonoids
  • Plant Extracts
  • Tritium
  • Vinblastine
  • Cyclosporine
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • naringenin
  • naringin