Inhibition of drug transport by genistein in multidrug-resistant cells expressing P-glycoprotein

Biochem Pharmacol. 1997 Jan 10;53(1):89-93. doi: 10.1016/s0006-2952(96)00657-0.


It has been claimed that the flavonoid genistein could be used to distinguish multidrug-resistant tumors expressing the multidrug resistance-associated protein (MRP) from those expressing P-glycoprotein (Pgp). Genistein would be block drug transport by MRP without affecting Pgp-mediated drug transport. However, we found that exposure to 200 microM genistein elicited an elevation in intracellular accumulation of rhodamine 123 (R123) and daunorubicin (DNR) in Pgp-expressing cell lines. Genistein inhibited R123 efflux in a rapidly reversible manner (ca. 2 min). The flavonoid also decreased photoaffinity labeling of Pgp by [3H]azidopine, a Pgp substrate. The present results show that genistein interacts with Pgp and inhibits Pgp-mediated drug transport. Hence, genistein cannot be used in simple assays to distinguish MRP- and Pgp-expressing cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP-Binding Cassette Transporters / physiology
  • Animals
  • Biological Transport / drug effects
  • Daunorubicin / pharmacokinetics
  • Drug Resistance, Multiple
  • Enzyme Inhibitors / pharmacology*
  • Genistein
  • Humans
  • Isoflavones / pharmacology*
  • Mice
  • Multidrug Resistance-Associated Proteins
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Rhodamine 123
  • Rhodamines / metabolism
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Enzyme Inhibitors
  • Isoflavones
  • Multidrug Resistance-Associated Proteins
  • Rhodamines
  • Rhodamine 123
  • Genistein
  • Protein-Tyrosine Kinases
  • Daunorubicin