Open AccessLong‐lasting Accumulation of Vinblastine in Inostamycin‐treated Multidrug‐resistant KB Cells
Author(s) -
Kawada Manabu,
Umezawa Kazuo
Publication year - 1991
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1991.tb01771.x
Subject(s) - vinblastine , microgram , efflux , multiple drug resistance , ic50 , mechanism of action , in vitro , pharmacology , chemistry , microbiology and biotechnology , biology , biochemistry , chemotherapy , antibiotics , genetics
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 [ 3 H] 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 [ 3 H] vinblastine efflux from KB‐C4 cells, but not from KB‐3‐1 cells, and inhibited [ 3 H] vinblastine binding to KB‐C4 membranes with an IC 5O of 0.94 μg/ml (1.3 μ M ). Furthermore, [ 3 H] vinblastine accumulated by treatment with 1 /μg/ml of inostamycin was resistant to efflux from KB‐C4 cells, even after the removal of inostamycin.