Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells

Br J Cancer. 1993 Nov;68(5):939-46. doi: 10.1038/bjc.1993.458.


In tumour cells the pharmacological basis for multidrug resistance (MDR) often appears to be a reduced cellular cytostatic drug accumulation caused by the drug efflux protein, P-glycoprotein (Pgp MDR), or by other drug transporters (non-Pgp MDR). Here we report the reversal of the decreased daunorubicin (DNR) accumulation in five non-Pgp MDR cell lines (GLC4/ADR, SW-1573/2R120, HT1080/DR4, MCF7/Mitox and HL60/ADR) by genistein. Genistein inhibited the enhanced DNR efflux in the GLC4/ADR cells. In these cells the decreased VP-16 accumulation was also reversed by genistein. Three other (iso)flavonoids biochanin A, apigenin and quercetin also increased the DNR accumulation in the GLC4/ADR cells. In contrast to the effects on non-Pgp MDR cells, 200 microM genistein did not increase the reduced DNR accumulation in three Pgp MDR cell lines (SW-1573/2R160, MCF7/DOX40 and KB8-5) or in the parental cell lines. In conclusion the use of genistein provides a means to probe non-Pgp related drug accumulation defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Alkaloids / pharmacology
  • Biological Transport / drug effects
  • Carrier Proteins / physiology*
  • Daunorubicin / pharmacokinetics*
  • Doxorubicin / pharmacokinetics
  • Drug Resistance*
  • Etoposide / pharmacokinetics
  • Genistein
  • Humans
  • Hydrogen-Ion Concentration
  • Isoflavones / pharmacology*
  • Lung Neoplasms / metabolism
  • Membrane Glycoproteins / physiology*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Staurosporine
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Alkaloids
  • Carrier Proteins
  • Isoflavones
  • Membrane Glycoproteins
  • Etoposide
  • Doxorubicin
  • Genistein
  • Protein-Tyrosine Kinases
  • Staurosporine
  • Tetradecanoylphorbol Acetate
  • Daunorubicin