Evaluation of the in vivo antitumor activity and in vitro cytotoxic properties of auranofin, a coordinated gold compound, in murine tumor models.
The coordinated gold compound, 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S-triethyl phosphine gold (auranofin; Ridaura), was evaluated for antitumor activity in a variety of mouse tumor models. Of the 15 tumor models evaluated, auranofin was found to be active only against i.p. P388 leukemia. A number of dose schedules was used to measure activity against P388 with optimal activity observed at 12 mg/kg given daily, i.p., on Days 1 to 5. Auranofin was active against i.p. P388 leukemia only when administered i.p.; the drug was completely inactive when administered i.v., s.c., or p.o. on Days 1 to 5. Evaluation of the effects of auranofin in vitro demonstrated that survival curves for B16 melanoma cells as measured by the clongenic and dye exclusion assays were exponential and monophasic; cell cycle distribution was not altered, and auranofin displayed no preferential cytotoxicity to logarithmic or plateau growth phase cell populations; auranofin inhibited DNA, RNA, and protein synthesis at cytotoxic concentrations but showed no selective effect; the cytotoxic activity and cellular association of gold from auranofin were dose, time, and temperature dependent; and binding of auranofin gold to serum proteins markedly decreased cellular uptake of gold and cytotoxicity of auranofin in vitro.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006046:Gold / Q000031:analogs & derivatives*; D007700:Kinetics; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold