Effect of XIAP inhibitors on the sensitivity of CD40-activated CLL cells to CD95-mediated apoptosis. CLL cells were activated via coculture with CD154-bearing cells and then examined 24 hours later for sensitivity to CD95-mediated apoptosis (depicted as decrease in viability, measured by DiOC6 staining). These cells were treated with 1540-14 (left panel) or its inactive structural analog, 1540-20 (right panel), at various concentrations as indicated at the bottom of each panel. The viability of the treated CLL cells relative to that of CLL cells cultured in medium alone is indicated on the y-axis. In each experiment, the viability of CLL cells cultured in medium alone exceeded 80%. Depicted are the relative viability measurements of CLL cells cultured with either compound alone (▪), either compound with zVAD-fmk (□), either compound plus CH11 (▴), or either compound with both CH11 and zVAD-fmk (▵). Relative viability of treatment with CH11, zVAD-fmk, and medium alone is shown at 0 μM. The errors indicate the SE about the mean of triplicate wells.
