Figure 5

Celecoxib-induced cell death in rheumatoid arthritis fibroblast-like synoviocytes is caspase-independent. Effect of caspase inhibition on celecoxib-induced cell death. Cells were pre-treated with caspase inhibitors (pancasp-In: pan-caspase inhibitor z-VAD-fmk; casp3-In: caspase 3 inhibitor z-DEVD-fmk) or control inhibitor z-FA-fmk (co-In: control inhibitor) for 1 hour and subsequently cultured in the presence of either 60 μM celecoxib or 0.5 nM tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for an additional 24 hours. Cells pre-treated only with solvent (dimethyl sulfoxide [DMSO]) served as controls. Cell death was determined using Annexin V binding and TO-PRO-3 uptake and expressed as relative cell death. (For this, cell death induced by TRAIL or celecoxib plus inhibitor was first subtracted by cell death of cells treated with inhibitor alone and then expressed as percentage versus cell death induced by TRAIL or celecoxib alone.) Data from three patients were averaged and are shown as the mean ± standard error of the mean.