RESORTHIOMYCIN, A NOVEL ANTITUMOR ANTIBIOTIC

III. POTENTIATION OF ANTITUMOR DRUGS AND ITS MECHANISM OF ACTION

Abstract

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 40μg/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 40μg/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 40μg/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.