Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150- to 170-kDa protein detected by photoaffinity labeling

M. M. Cornwell, A. R. Safa, R. L. Felsted, M. M. Gottesman, I. Pastan

Research output: Contribution to journalArticle

311 Scopus citations

Abstract

Multiple durg resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-restistant human KB carcinoma cell lines exhibit increased specific and saturable binding of vinblastine. To identify the molecules that bind vinblastine, membrane vesicles from multidrug-resistant cells were exposed to two analogs of vinblastine, N-(p-azido-[3,5-3H]benzoyl)-N'-(β-aminoethyl)vindesine and N-(p-azido-[3-125I]salicyl)-N'-(β-aminoethyl)vindesine, that could be photoactivated. Our studies show the specific labeling of a 150- to 170-kDa protein in membrane vesicles from two independently selected multidrug-resistant KB cell lines, which was not seen in drug-sensitive parental or revertant cell lines. The labeling of the high molecular weight protein was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at about 1 μM. Photolabeling was also inhibited by 100 μM vincristine or 100 μM verapamil but not by 100 μM colchicine or 100 μM dexamethasone. The data suggest that the 150- to 170-kDa protein may play an important role in the multidrug-resistance phenotype.

Original languageEnglish (US)
Pages (from-to)3847-3850
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number11
DOIs
StatePublished - Jan 1 1986
Externally publishedYes

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