Decreased intracellular mitoxantrone in resistant MCF-7 breast cancer cells is attributed to an energy dependent efflux
AuthorParrish, Pamela Ruth, 1965-
AdvisorDalton, William S.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractIntracellular drug accumulation was studied in two drug resistant variants of the human breast cancer MCF-7 (MCF/7) cell line selected with mitoxantrone (MCF7/Mitox) and doxorubicin (MCF7/D40). Earlier studies show that both cell lines have similar cell cycle characteristics, and both are multidrug resistant. Previously, P-glycoprotein was detected in MCF7/D40, but not in MCF7/Mitox. Both cell lines, however, display decreased drug accumulation. The P-glycoprotein chemo-modulator verapamil increased mitoxantrone accumulation 1.6 fold in MCF7/D40 cells, thus achieving identical intracellular drug levels to the MCF7/S cell line. Verapamil had little effect on drug accumulation in MCF7/Mitox cells. Rapid influx of mitoxantrone from 5 seconds to 60 seconds was not significantly different between MCF7/Mitox and MCF7/S. Influx in the MCF7/D40 cell line was greater than in the MCF7/Mitox or MCF7/S cell lines. Decreased drug accumulation was found to be at least partly due to enhanced drug efflux. Depletion of 73.9% to 88.9% of cellular ATP by sodium azide (NaN3) decreased the efflux of mitoxantrone in each cell line, thus demonstrating an energy dependence of drug efflux.