title: BAY 11-7082 induces cell death through NF-kappaB-independent mechanisms in the Ewing's sarcoma family of tumours.
abstract: 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.
authors.affiliation: Candlelighter's Children's Cancer Research Group, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, UK. d.white@leeds.ac.uk
authors.forename: Danielle E
authors.initials: DE
authors.lastname: White
authors.forename: Susan A
authors.initials: SA
authors.lastname: Burchill
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D017313:Fenretinide / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000473:pathology; D013450:Sulfones / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009570:Nitriles; D017382:Reactive Oxygen Species; D013450:Sulfones; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D017313:Fenretinide; D048051:p38 Mitogen-Activated Protein Kinases