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

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

Research output: Contribution to journalArticle

311 Citations (Scopus)

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
StatePublished - 1986
Externally publishedYes

Fingerprint

Vinblastine
Vindesine
KB Cells
Membranes
Cell Line
Neoplasms
Proteins
Colchicine
Multiple Drug Resistance
Vincristine
Verapamil
Dexamethasone
Membrane Proteins
Molecular Weight
Carcinoma
Phenotype
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150- to 170-kDa protein detected by photoaffinity labeling. / Cornwell, M. M.; Safa, Ahmad; Felsted, R. L.; Gottesman, M. M.; Pastan, I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 83, No. 11, 1986, p. 3847-3850.

Research output: Contribution to journalArticle

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AU - Pastan, I.

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