Figure 8.

TRAIL induces apoptosis of normal but not cancerous prostate cells through an AEBSF-sensitive activity. Normal prostate epithelial cells and DU145 prostate cancer cells were treated with cycloheximide alone (control) or cycloheximide plus recombinant TRAIL in the presence of zVAD.fmk or AEBSF as indicated. Cell survival was determined by microscopy after 24 h. TRAIL killed both normal and cancerous prostate cells. The caspase inhibitor zVAD.fmk efficiently prevented cell death in the DU145 cells but did not prevent death in normal prostate cells. The addition of AEBSF and zVAD.fmk did prevent death of normal cells. These data indicate that TRAIL activates cell death pathways in normal prostate cells that have the same requirement for both caspase- and serine protease-dependent signals as FADD-DD.