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Membrane vesicles from multidrug-resistant human carcinoma cells contain a specific 150,000-170,000 dalton protein detected by photoaffinity labeling

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:7025283
; ; ; ;
The authors have selected multidrug-resistant human KB carcinoma cells in high levels of colchicine (KB-C4) or vinblastine (KB-V1) which are cross-resistant to many other structurally unrelated chemotheraputic agents. To determine the mechanism of reduced drug accumulation, they measured /sup 3/H-vinblastine (/sup 3/H-VBL) association with membrane vesicles made from parental drug sensitive, drug-resistant and revertant cells. Membrane vesicles from highly multidrug resistant cells exhibited increased specific and saturable binding of vinblastine, (Kd = 1 ..mu..M) that was temperature dependent and trypsin sensitive. To identify the molecules which bind vinblastine, membrane vesicles were exposed to two photo-activatable analogs of vinblastine, (N-P-(azido-3,5,-(/sup 3/H)-benzoyl)-N'-..beta..-aminoethylvindisine (/sup 3/H-NAB) and N-P-(azido-3-(/sup 125/I)-solicyl)-N'-..beta..-aminoethylvindesine (/sup 125/I-NASV). The specific labeling of a 150,000-170,000 dalton protein in membrane vesicles from multidrug-resistant KB-C4 and KB-V1 cells was found. /sup 125/I-NASV labeling was inhibited by vinblastine, vincrinstine and verapamil but not by colchicine or dexamethasone. The 150,000-170,000 dalton protein may have an important role in the multidrug resistance phenotype.
Research Organization:
National Institute of Health, Bethesda, MD
OSTI ID:
7025283
Report Number(s):
CONF-8606151-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALKALOIDS
ANIMAL CELLS
ANTIMITOTIC DRUGS
ANTIPYRETICS
AROMATICS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARCINOMAS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COLCHICINE
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
MEMBRANES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOTYPE
PROTEINS
PYRROLES
RADIOISOTOPES
REACTION KINETICS
SENSITIVITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
VINBLASTINE