bay-11-7082 and Sarcoma--Ewing

The role of NF-kappaB in the Ewing's sarcoma family of tumours (ESFT) and their response to fenretinide has been investigated. Basal levels of phosphorylated NF-kappaB were low in all ESFT cells. BAY 11-7082 decreased cell viability, which was accompanied by caspase-3 cleavage. This was independent of the increase in reactive oxygen species, p38(MAPK) phosphorylation and expression of NF-kappaB target proteins. NF-kappaB knockdown did not induce death under normal growth conditions, but did reduce TNFalpha-dependent cell survival. Fenretinide-induced apoptosis was independent of NF-kappaB. BAY 11-7082-induced cell death through an NF-kappaB-independent mechanism and enhanced cell death when combined with fenretinide.

Topics: Apoptosis; Bone Neoplasms; Cell Line, Tumor; Fenretinide; Humans; I-kappa B Proteins; NF-kappa B; NF-KappaB Inhibitor alpha; Nitriles; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Reactive Oxygen Species; Sarcoma, Ewing; Sulfones; Transcription Factor RelA; Tumor Necrosis Factor-alpha