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Titre du document / Document title

Oleandrin suppresses activation of nuclear transcription factor-κB, activator protein-1, and c-jun NH2-Terminal kinase

Auteur(s) / Author(s)

MANNA S. K. (1) ; SAH N. K. (1) ; NEWMAN R. A. (2) ; CISNEROS A. (2) ; AGGARWAL B. B. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, ETATS-UNIS
(2) Pharmaceutical Development Center, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, ETATS-UNIS

Résumé / Abstract

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 other agents and inhibited the TNF-induced activation of c-Jun NH2-terminal kinase. Overall, our results indicate that oleandrin inhibits activation of NF-κB and AP-1 and their associated kinases. This may provide a molecular basis for the ability of oleandrin to suppress inflammation and perhaps tumorigenesis.

Revue / Journal Title

Cancer research    ISSN  0008-5472   CODEN CNREA8 

Source / Source

2000, vol. 60, no14, pp. 3838-3847 (58 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Association for Cancer Research, Philadelphia, PA, ETATS-UNIS  (1941) (Revue)

Mots-clés anglais / English Keywords

Glycoside

;

Polyphenol

;

Nerium oleander

;

Plant origin

;

Plant leaf

;

Human

;

Animal

;

Established cell line

;

In vitro

;

Biological activity

;

Antineoplastic agent

;

Transcription factor

;

Nuclear protein

;

Protein kinase

;

C-Onc gene

;

Antiinflammatory agent

;

Transcription factor NFκB

;

Transcription factor AP1

;

Apocynaceae

;

Dicotyledones

;

Angiospermae

;

Spermatophyta

;

Transferases

;

Enzyme

;

Mots-clés français / French Keywords

Glycoside

;

Polyphénol

;

Nerium oleander

;

Origine végétale

;

Feuille végétal

;

Homme

;

Animal

;

Lignée cellulaire établie

;

In vitro

;

Activité biologique

;

Anticancéreux

;

Facteur transcription

;

Protéine nucléaire

;

Protein kinase

;

Gène onc cellulaire

;

Antiinflammatoire

;

Oléandrine

;

Gène jun

;

Facteur transcription NFκB

;

Facteur transcription AP1

;

Apocynaceae

;

Dicotyledones

;

Angiospermae

;

Spermatophyta

;

Transferases

;

Enzyme

;

Mots-clés espagnols / Spanish Keywords

Glicósido

;

Polifenol

;

Nerium oleander

;

Origen vegetal

;

Hoja vegetal

;

Hombre

;

Animal

;

Línea celular establecida

;

In vitro

;

Actividad biológica

;

Anticanceroso

;

Factor transcripción

;

Proteína nuclearia

;

Protein kinase

;

Gen onc celular

;

Antiinflamatorio

;

Apocynaceae

;

Dicotyledones

;

Angiospermae

;

Spermatophyta

;

Transferases

;

Enzima

;

Localisation / Location

INIST-CNRS, Cote INIST : 5088, 35400009037137.0260

Nº notice refdoc (ud4) : 1472360



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