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 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.

• Authors: M Tahara, A Tomida, T Nishimura, H Yamaguchi, H Suzuki
• Journal: The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 43 Issue 2 Pg. 138-42 (Feb 1990) ISSN: 0021-8820 [Print] England
• PMID: 2312403 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Resorcinols
• resorthiomycin
• Dactinomycin
• Vincristine
• Deoxyglucose
• Thymidine

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Cell Division (drug effects)
• Cell Line (drug effects)
• Cell Survival (drug effects)
• Cricetinae
• Dactinomycin (pharmacology)
• Deoxyglucose (metabolism)
• Drug Synergism
• Humans
• Mice
• Resorcinols (pharmacology)
• Thymidine (metabolism)
• Vincristine (pharmacology)