Induction of mammalian stress proteins by a triethylphosphine gold compound used in the therapy of rheumatoid arthritis

In vitro exposure of cultured human, murine and rat cells to pharmacologic concentrations (10^-8 to 10^-6M) of auranofin, 2,3,4,6,-tetra-O-acetyl-1-thio-β-D-glucopyranosato-S-triethylphosphine gold(I) (Ridaura^TM), a gold containing compound approved for the treatment of rheumatoid arthritis, results in the induction of several stress proteins. The enhanced synthesis of two polypeptides, p32 and p34, was particularly prominent. A similar response was observed in freshly collected human monocytes challenged with auranofin. In addition, oral administration of auranofin to rats induced enhanced synthesis of a 32-kDa protein in peritoneal exudate cells analyzed ex vivo at various times following drug treatment. These data suggest that increased synthesis of p32 and p34 might participate in mediating certain aspects of auranofin pharmacology.