P-glycoprotein mediates profound resistance to bisantrene

Bisantrene, mitoxantrone, and anthracyclines are anthracene derivatives that interact with DNA and are used for the treatment of cancers. The mechanisms of resistance to bisantrene are unknown. Here we show that cells that overexpress low levels of P-glycoprotein or are transfected with human MDR1 h...

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Bibliographic Details
Published inOncology research Vol. 6; no. 7; p. 291
Main Authors Zhang, X P, Ritke, M K, Yalowich, J C, Slovak, M L, Ho, J P, Collins, K I, Annable, T, Arceci, R J, Durr, F E, Greenberger, L M
Format Journal Article
LanguageEnglish
Published United States 1994
Subjects
Anthracenes - pharmacology
Antibiotics, Antineoplastic - pharmacology
Antineoplastic Agents - pharmacology
ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Base Sequence
Chromosome Banding
Chromosomes, Human
Clone Cells
Colonic Neoplasms
DNA Primers
Drug Resistance, Multiple
Humans
In Situ Hybridization, Fluorescence
KB Cells
Melanoma
Molecular Sequence Data
Polymerase Chain Reaction
Recombinant Proteins - biosynthesis
Recombinant Proteins - metabolism
Transfection
Tumor Cells, Cultured
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Summary:Bisantrene, mitoxantrone, and anthracyclines are anthracene derivatives that interact with DNA and are used for the treatment of cancers. The mechanisms of resistance to bisantrene are unknown. Here we show that cells that overexpress low levels of P-glycoprotein or are transfected with human MDR1 have approximately 10-fold greater resistance to bisantrene compared to vinblastine, doxorubicin, or colchicine. Furthermore, bisantrene can be used to select for high-level P-glycoprotein-mediated multiple drug resistance in a human colon carcinoma cell line, LS 174T, and the drug blocks photoaffinity labeling of P-glycoprotein. The data suggest that bisantrene is an excellent substrate for P-glycoprotein. These findings could influence subsequent clinical evaluation of bisantrene for the treatment of cancer.
ISSN:0965-0407