Regulation of TRAIL-Induced Apoptosis by Transcription Factors

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a newly identified member of the TNF family. Unlike many other members of the TNF family, TRAIL selectively induces apoptosis of tumor cells, but not normal cells. The mechanisms whereby TRAIL-induced apoptosis is regulated in various cell types are not clear. We report here that the peroxisome proliferator-activated receptor (PPAR)-γ and nuclear factor (NF)-κB play distinct roles in regulating TRAIL-induced apoptosis. Activation of PPAR-γ by its agonist pioglitazone significantly enhanced TRAIL-induced apoptosis. This was associated with inhibition of proliferation and cell cycle progression. On the other hand, inhibition of NF-κB by sulfasalazine also significantly enhanced TRAIL-induced apoptosis. These results strongly suggest that while transcription factor PPAR-γ promotes TRAIL-induced apoptosis, NF-κB inhibits it. Thus, PPAR-γ agonists and NF-κB inhibitors are potent enhancers of TRAIL-induced apoptosis.