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

C. H M Versantvoort, G. J. Schuurhuis, H. M. Pinedo, C. A. Eekman, C. M. Kuiper, J. Lankelma, H. J. Broxterman

Research output: Contribution to journalArticlepeer-review

Abstract

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 μm 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.

Original languageEnglish (US)
Pages (from-to)939-946
Number of pages8
JournalBritish Journal of Cancer
Volume68
Issue number5
StatePublished - Nov 1993
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells'. Together they form a unique fingerprint.

Cite this