Energy-dependent processes involved in reduced drug accumulation in multidrugresistant human lung cancer cell lines without P-glycoprotein expression

Carolina H M Versantvoort, Henricus J. Broxterman, Herbert M. Pinedo, Elisabeth G E De Vries, Nicole Feller, Catharina M. Kuiper, Jan Lankelma

Research output: Contribution to journalArticlepeer-review

Abstract

Mechanisms contributing to reduced cytotoxic drug accumulation were studied in two multidrug-resistant (MDR) human lung cancer cell lines without P-glycoprotein expression. In these (non-small cell) SW-1573/ 2R120 and (small cell) GLC4/ADR MDR cells, the steady-state accumulation of [14C]daunorubicin was 30 and 12%, respectively, of that in the parent cells. When cells, at steady state, were permeabilized with digitonin, the amount of daunorubicin binding increased only in the resistant cells. The reduced accumulation of daunorubicin in the SW-1573/2R120 and GLC4/ADR cells was accompanied by a lower initial (2 min) uptake rate of this drug. No difference in initial efflux rate of daunorubicin from preloaded cells could be detected between sensitive and resistant SW-1573 cells. However, daunorubicin was extruded 5-fold faster from GLC4/ADR cells than from the parental cells. In the presence of the energy metabolism inhibitors sodium azide and deoxyglucose, the reduced daunorubicin accumulations in the SW-1573/2R120 and GLC4/ ADR MDR cells were (almost) completely reversed. The effects of these inhibitors on drug uptake were already apparent during the earliest measured time points (

Original languageEnglish (US)
Pages (from-to)17-23
Number of pages7
JournalCancer Research
Volume52
Issue number1
StatePublished - Jan 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint

Dive into the research topics of 'Energy-dependent processes involved in reduced drug accumulation in multidrugresistant human lung cancer cell lines without P-glycoprotein expression'. Together they form a unique fingerprint.

Cite this