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. 1991 Oct;82(10):1160–1164. doi: 10.1111/j.1349-7006.1991.tb01771.x

Long‐lasting Accumulation of Vinblastine in Inostamycin‐treated Multidrug‐resistant KB Cells

Manabu Kawada 1, Kazuo Umezawa 1
PMCID: PMC5918255  PMID: 1955381

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 μg/ml, while it did not enhance accumulation in the drug‐sensitive KB‐3‐1 cells. At a concentration of 1 μ/ 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 IC5O of 0.94 μg/ml (1.3 μM). Furthermore, [3H] vinblastine accumulated by treatment with 1 /μg/ml of inostamycin was resistant to efflux from KB‐C4 cells, even after the removal of inostamycin.

Keywords: KB cells, Inostamycin, Multidrug resistance

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