Détail de la notice
Titre du Document
Oleandrin suppresses activation of nuclear transcription factor-κB, activator protein-1, and c-jun NH2-Terminal kinase
Auteur(s)
MANNA S. K. ; SAH N. K. ; NEWMAN R. A. ; ...
Résumé
Agents that can suppress the activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) may be able to block tumorigenesis and inflammation. Oleandrin, a polyphenolic cardiac glycoside derived from the leaves of Nerium oleander, is a candidate NF-κB and AP-1 modulator. We investigated the effect of oleandrin on NF-KB activation induced by inflammatory agents. Oleandrin blocked tumor necrosis factor (TNF)-induced activation of NF-KB in a concentration- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of IκBα, an inhibitor of NF-κB. A proprietary hot water extract of oleander (Anvirzel) also blocked TNF-induced NF-κB activation; subsequent fractionation of the extract revealed that this activity was attributable to oleandrin. The effects of oleandrin were not cell type specific, because it blocked TNF-induced NF-KB activation in a variety of cells. NF-KB-dependent reporter gene transcription activated by TNF was also suppressed by oleandrin. The TNF-induced NF-KB activation cascade involving TNF receptor 1/TNF receptor-associated death domain/TNF receptor-associated factor 2/NF-κB-inducing kinase/IκBα kinase was interrupted at the TNF receptor-associated factor 2 and NF-KB-inducing kinase sites by oleandrin, thus suppressing NF-κB reporter gene expression. Oleandrin blocked NF-KB activation induced by phorbol ester and lipopolysaccharide. Oleandrin also blocked AP-1 activation induced by TNF and oth
Editeur
American Association for Cancer Research
Identifiant
PMID : 10919658 ISSN : 0008-5472 CODEN : CNREA8
Source
Cancer research (Baltimore) A. 2000, vol. 60, n° 14, pp. 3838-3847 [bibl. : 58 ref.]
Langue
Anglais
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