title: Long-lasting accumulation of vinblastine in inostamycin-treated multidrug-resistant KB cells.
abstract: Inostamycin, a novel polyether compound, reverses multidrug resistance in KB cells. The mechanism of its action was studied by use of radioactively labeled vinblastine. Inostamycin dose-dependently increased the accumulation of [3H]vinblastine in multidrug-resistant KB-C4 cells at 0.5-2 micrograms/ml, while it did not enhance accumulation in the drug-sensitive KB-3-1 cells. At a concentration of 1 microgram/ml inostamycin inhibited active [3H]vinblastine efflux from KB-C4 cells, but not from KB-3-1 cells, and inhibited [3H]vinblastine binding to KB-C4 membranes with an IC50 of 0.94 microgram/ml (1.3 microM). Furthermore, [3H]vinblastine accumulated by treatment with 1 microgram/ml of inostamycin was resistant to efflux from KB-C4 cells, even after the removal of inostamycin.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama.
authors.forename: M
authors.initials: M
authors.lastname: Kawada
authors.forename: K
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D004351:Drug Resistance; D005663:Furans / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000378:metabolism; D014747:Vinblastine / Q000378:metabolism*
chemical_list: D005663:Furans; C071861:inostamycin; D014747:Vinblastine; D014700:Verapamil