Evaluation of the in vivo antitumor activity and in vitro cytotoxic properties of auranofin, a coordinated gold compound, in murine tumor models

• Published in: Cancer research (Chicago, Ill.) Ill.), 1985, Vol.45 (1), p.32-39
• Main Authors: MIRABELLI, C. K, JOHNSON, R. K, CHIU MEI SUNG, FAUCETTE, L, MUIRHEAD, K, CROOKE, S. T
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Auranofin; Aurothioglucose - analogs & derivatives; Aurothioglucose - therapeutic use; Aurothioglucose - toxicity; Biological and medical sciences; Cell Cycle - drug effects; Cell Survival - drug effects; Chemotherapy; Drug Evaluation, Preclinical; Gold - analogs & derivatives; Kinetics; Leukemia P388 - drug therapy; Leukemia P388 - pathology; Leukemia, Experimental - drug therapy; Medical sciences; Melanoma - drug therapy; Melanoma - pathology; Mice; Mice, Inbred DBA; Mice, Inbred Strains; Pharmacology. Drug treatments; Tumor Stem Cell Assay
• ISSN: 0008-5472; 1538-7445

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.