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Biomedical subjects

T Sumizawa

Publications and source records attributed to T Sumizawa.

56 records · Page 4Linked to original sources
PubMed1989

Correlation between reversing of multidrug resistance and inhibiting of [3H]azidopine photolabeling of P-glycoprotein by newly synthesized dihydropyridine analogues in a human cell line.

Ten synthetic dihydropyridine analogues were investigated for their ability to reverse drug resistance in a multidrug-resistant human carcinoma cell line, KB-Cl. Four dihydropyridine analogues completely reversed the resistance, three lowered the resistance, and three had little effect. The radioactive photoactive dihydropyridine calcium channel blocker, [3H]azidopine, photolabels P-glycoprotein in membrane vesicles from KB-Cl cells. This photolabeling was almost completely inhibited by excess dihydropyridine analogues that reversed or lowered drug resistance. In contrast, the labeling was not significantly inhibited by analogues that do not reverse resistance. Among other reversing agents, cepharanthine and reserpine inhibited the [3H]azidopine photolabeling, but thioridazine did not. N-Solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine slightly inhibited the labeling at 100 microM. An anticancer agent, vinblastine, also inhibited the labeling. The correlation between the reversing of the drug resistance and the inhibition of the [3H]azidopine photolabeling of P-glycoprotein by dihydropyridine analogues suggests a role for P-glycoprotein in multidrug resistance and also the reversing of the resistance by dihydropyridine analogues.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Synthetic isoprenoid photoaffinity labeling of P-glycoprotein specific to multidrug-resistant cells.

The synthetic isoprenoid N-solanesyl-N,N'-bis(3,4-dimethoxy-benzyl)ethylenediamine (SDB) is known to reverse drug resistance in human multidrug-resistant KB cells. SDB inhibits the photolabeling of P-glycoprotein with the vinblastine analog N-(pazido-(3-(125)l)salicyl)-N'-beta-aminoethylvindesine. We synthesized photoactive radioactive SDB and used it to photoaffinity label membrane vesicles from human KB cells and their multidrug-resistant subline KB-C2 cells. A 150 to 170 kDa protein in membrane vesicles from KB-C2 cells was specifically labeled by the photoanalog of SDB. The labeled band was not detectable in parenteral drug-sensitive cells. The photolabeled 150 to 170 kDa protein was immunoprecipitated with a monoclonal antibody (C219) specific to P-glycoprotein. P-glycoprotein labeling was inhibited by anticancer agents, vinblastine, vincristine, actinomycin D, and daunomycin, with half-maximal inhibition at 2.0, 2.3, 18, and 23 microM, respectively. Only 33 and 18% of the labeling was inhibited by 100 microM Adriamycin and colchicine, respectively. The labeling was also inhibited by agents that reverse multidrug resistance, such as verapamil, reserpine, cepharanthine, and SDB. The existence of other molecules that specifically bind to 125l-SDB-photoanalog was suggested in both KB and KB-C2 membrane vesicles. The fact that we could identify the synthetic isoprenoid acceptor in membrane vesicles from multidrug-resistant cells confirms that P-glycoprotein plays a role in the multidrug resistance phenotype and provides an explanation for the fact that SDB circumvents multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗