Decreased intracellular mitoxantrone in resistant MCF-7 breast cancer cells is attributed to an energy dependent efflux

Persistent Link:
http://hdl.handle.net/10150/278582
Title:
Decreased intracellular mitoxantrone in resistant MCF-7 breast cancer cells is attributed to an energy dependent efflux
Author:
Parrish, Pamela Ruth, 1965-
Issue Date:
1990
Publisher:
The University of Arizona.
Rights:
Copyright © 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.
Abstract:
Intracellular 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.
Type:
text; Thesis-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Health Sciences, Oncology.
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Graduate College
Degree Grantor:
University of Arizona
Advisor:
Dalton, William S.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleDecreased intracellular mitoxantrone in resistant MCF-7 breast cancer cells is attributed to an energy dependent effluxen_US
dc.creatorParrish, Pamela Ruth, 1965-en_US
dc.contributor.authorParrish, Pamela Ruth, 1965-en_US
dc.date.issued1990en_US
dc.publisherThe University of Arizona.en_US
dc.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.en_US
dc.description.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.en_US
dc.typetexten_US
dc.typeThesis-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectHealth Sciences, Oncology.en_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorDalton, William S.en_US
dc.identifier.proquest1342670en_US
dc.identifier.bibrecord.b26592824en_US
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