Circumvention of multidrug resistance in human carcinoma KB cells by polyether antibiotics.
We examined the effect of various polyether antibiotics on colchicine resistance in multidrug-resistant KB-C4 cells which exhibit about 4,000-fold resistance to colchicine. As a result, 4 out of 14 polyether antibiotics were found to reverse colchicine resistance. Among them, laidlomycin was the most potent. It potentiated colchicine cytotoxicity on KB-C4 cells about 700-fold at 1 microgram/ml. Degree of potentiation was calculated by dividing of the IC50 value of colchicine in the absence of a polyether antibiotic by the IC50 value of colchicine in the presence of the polyether antibiotic. Monensin, dianemycin, and leuseramycin at 3 micrograms/ml also potentiated the cytotoxicity, about 100-fold. We previously reported that inostamycin is a potent chemosensitizer in KB-C4 cells. Although lysocellin has a structure very similar to that of inostamycin, it didn't reverse colchicine resistance. It slightly increased [3H]vinblastine accumulation in KB-C4 cells and weakly inhibited the [3H]vinblastine binding to KB-C4 plasma membranes.
Kawada
M
M
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Sumi
S
S
Umezawa
K
K
Inouye
S
S
Sawa
T
T
Seto
H
H
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004987:Ethers; D006801:Humans; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004987:Ethers; D014747:Vinblastine; D003078:Colchicine