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 leuke...

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Bibliographic Details
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
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Summary: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.
ISSN:0008-5472
1538-7445