GENERATION OF REACTIVE OXYGEN SPECIES IS REQUIRED FOR BUCILLAMINE, A NOVEL ANTIRHEUMATIC DRUG, TO INDUCE APOPTOSIS IN CONCERT WITH COPPER

Rheumatoid arthritis (RA) is considered to be a proliferative disorder of synovial tissue, which is composed of macrophage-like, fibroblast- like and dendritic cells. Bucillamine (BUG) is a novel disease-modifyi ng anti-rheumatic drug, which is a structural analogue of cysteine. So me of the pharmacological actions of BUC have been shown to depend on the generation of reactive oxygen species (ROS) in the presence of cop per. In this study, we examined whether BUC in concert with copper can induce apoptosis via generation of ROS. THP.1, a human monocytic cell line, was used as surrogate for synovial cells. We observed that BUC plus copper can induce THP.1 to undergo apoptosis, as evidenced by the presence of DNA degradation, which is preceded by ROS generation and increase in membrane permeability. Moreover, catalase rescued THP.1 fr om BUG-mediated cell death, indicating that generation of ROS is essen tial for the induction of apoptosis. Red blood cells (RBC), probably a cting as a scavenger of ROS, also rescued THP.1 from cell death mediat ed by BUC plus copper. Collectively, we suggest that ROS derived from BUC in the presence of copper may suppress the outgrowth of rheumatoid arthritis synovial cells in vivo through the induction of apoptosis.