EVALUATION OF THE INVIVO ANTITUMOR-ACTIVITY AND INVITRO CYTO-TOXIC PROPERTIES OF AURANOFIN, A COORDINATED GOLD COMPOUND, IN MURINE TUMOR-MODELS

Abstract

The coordinated Au compound, 2,3,4,6-tetra-O-acetyl-1-thio-.beta.-D-glucopyranosato-S-triethylphospine 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 1-5. 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 1-5. Evaluation on the effects of auranofin in vitro demonstrated that survival curves for B16 melanoma cells as measured by the clonogenic 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.