Regulation of TRAIL-induced apoptosis by transcription factors

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) i s a newly identified member of the TNF family. Unlike many other members of the TNF family, TRAIL selectively induces apoptosis of tumor cells, but no t normal cells. The mechanisms whereby TRAIL-induced apoptosis is regulated in various cell types are not clear. We report here that the peroxisome pr oliferator-activated receptor (PPAR)-gamma and nuclear factor (NF)-kappa B play distinct roles in regulating TRAIL-induced apoptosis. Activation of PP AR-gamma by its agonist pioglitazone significantly enhanced TRAIL-induced a poptosis, This was associated with inhibition of proliferation and cell cyc le progression. On the other hand, inhibition of NF-kappa B by sulfasalazin e also significantly enhanced TRAIL-induced apoptosis, These results strong ly suggest that while transcription factor PPAR-gamma promotes TRAIL-induce d apoptosis, NF-kappa B inhibits it. Thus, PPAR-gamma agonists and NF-kappa B inhibitors are potent enhancers of TRAIL-induced apoptosis. (C) 2000 Aca demic Press.