Resorthiomycin, a novel antitumor antibiotic. III. Potentiation of antitumor drugs and its mechanism of action.
Resorthiomycin suppressed the clonogenic activity of a multidrug-resistant mutant cell line of Chinese hamster V79 cells more potently than its parental cells. Moreover, resorthiomycin at 40 micrograms/ml potentiated the cytotoxic activity of vincristine and actinomycin D on V79 cells over 3-fold. Uptake of [3H]actinomycin D into V79 cells was stimulated 2-fold by 40 micrograms/ml of resorthiomycin during 2 hours incubation. On the other hand, incorporation of [3H]thymidine and [3H]uridine into mouse leukemia L5178Y cells was inhibited in a dose-dependent manner at resorthiomycin concentrations ranging from 5 to 40 micrograms/ml. In ATP-depleted L5178Y cells, membrane transport of [3H]thymidine and 2-[3H]deoxyglucose was strongly suppressed by resorthiomycin. These results suggest that resorthiomycin acts on the plasma membrane and perturbes some membrane function.
Tahara
M
M
Institute of Applied Microbiology, University of Tokyo, Japan.
Tomida
A
A
Nishimura
T
T
Yamaguchi
H
H
Suzuki
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003609:Dactinomycin / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D012118:Resorcinols / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D012118:Resorcinols; C063431:resorthiomycin; D003609:Dactinomycin; D014750:Vincristine; D003847:Deoxyglucose; D013936:Thymidine