File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Eriocalyxin B inhibits nuclear factor-κB activation by interfering with the binding of both p65 and p50 to the response element in a noncompetitive manner

TitleEriocalyxin B inhibits nuclear factor-κB activation by interfering with the binding of both p65 and p50 to the response element in a noncompetitive manner
Authors
Issue Date2006
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://www.molpharm.org
Citation
Molecular Pharmacology, 2006, v. 70 n. 6, p. 1946-1955 How to Cite?
AbstractNuclear factor-κB (NF-κB) has been recognized to play a critical role in cell survival and inflammatory processes. It has become a target for intense drug development for the treatment of cancer, inflammatory, and autoimmune diseases. Here, we describe a potent NF-κB inhibitor, eriocalyxin B (Eri-B), an ent-kauranoid isolated from Isodon eriocalyx, an anti-inflammatory remedy. The presence of two α,α-unsaturated ketones give this compound the uniqueness among the ent-kauranoids tested. Eri-B inhibited the NF-κB transcriptional activity but not that of cAMP response element-binding protein. It suppressed the transcription of NF-κB downstream gene products including cyclooxygenase-2 and inducible nitric-oxide synthase induced by tumor necrosis factor-α or lipopolysaccharide in macrophages and hepatocarcinoma cells. Chromatin immunoprecipitation assay indicated that Eri-B selectively blocked the binding between NF-κB and the response elements in vivo without affecting the nuclear translocation of the transcription factor. Down-regulation of the endogenous p65 protein sensitized the cells toward the action of the compound. Furthermore, in vitro binding assays suggested that Eri-B reversibly interfered with the binding of p65 and p50 subunits to the DNA in a noncompetitive manner. In summary, this study reveals the novel action of a potent NF-κB inhibitor that could be potentially used for the treatment of a variety of NF-κB-associated diseases. Modification of the structure of this class of compounds becomes the key to the control of the behavior of the compound against different cellular signaling pathways. Copyright © 2006 The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/168067
ISSN
2023 Impact Factor: 3.2
2023 SCImago Journal Rankings: 1.038
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, CHen_US
dc.contributor.authorGrill, SPen_US
dc.contributor.authorLam, Wen_US
dc.contributor.authorGao, Wen_US
dc.contributor.authorSun, HDen_US
dc.contributor.authorCheng, YCen_US
dc.date.accessioned2012-10-08T03:14:44Z-
dc.date.available2012-10-08T03:14:44Z-
dc.date.issued2006en_US
dc.identifier.citationMolecular Pharmacology, 2006, v. 70 n. 6, p. 1946-1955en_US
dc.identifier.issn0026-895Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/168067-
dc.description.abstractNuclear factor-κB (NF-κB) has been recognized to play a critical role in cell survival and inflammatory processes. It has become a target for intense drug development for the treatment of cancer, inflammatory, and autoimmune diseases. Here, we describe a potent NF-κB inhibitor, eriocalyxin B (Eri-B), an ent-kauranoid isolated from Isodon eriocalyx, an anti-inflammatory remedy. The presence of two α,α-unsaturated ketones give this compound the uniqueness among the ent-kauranoids tested. Eri-B inhibited the NF-κB transcriptional activity but not that of cAMP response element-binding protein. It suppressed the transcription of NF-κB downstream gene products including cyclooxygenase-2 and inducible nitric-oxide synthase induced by tumor necrosis factor-α or lipopolysaccharide in macrophages and hepatocarcinoma cells. Chromatin immunoprecipitation assay indicated that Eri-B selectively blocked the binding between NF-κB and the response elements in vivo without affecting the nuclear translocation of the transcription factor. Down-regulation of the endogenous p65 protein sensitized the cells toward the action of the compound. Furthermore, in vitro binding assays suggested that Eri-B reversibly interfered with the binding of p65 and p50 subunits to the DNA in a noncompetitive manner. In summary, this study reveals the novel action of a potent NF-κB inhibitor that could be potentially used for the treatment of a variety of NF-κB-associated diseases. Modification of the structure of this class of compounds becomes the key to the control of the behavior of the compound against different cellular signaling pathways. Copyright © 2006 The American Society for Pharmacology and Experimental Therapeutics.en_US
dc.languageengen_US
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://www.molpharm.orgen_US
dc.relation.ispartofMolecular Pharmacologyen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshChromatin Immunoprecipitationen_US
dc.subject.meshCyclooxygenase 2 - Metabolismen_US
dc.subject.meshDna Primersen_US
dc.subject.meshDiterpenes - Pharmacologyen_US
dc.subject.meshElectrophoretic Mobility Shift Assayen_US
dc.subject.meshHumansen_US
dc.subject.meshNf-Kappa B - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshNitric Oxide Synthase Type Ii - Metabolismen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshProtein Transporten_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Pharmacologyen_US
dc.titleEriocalyxin B inhibits nuclear factor-κB activation by interfering with the binding of both p65 and p50 to the response element in a noncompetitive manneren_US
dc.typeArticleen_US
dc.identifier.emailLeung, CH:duncanl@hkucc.hku.hken_US
dc.identifier.authorityLeung, CH=rp00730en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1124/mol.106.028480en_US
dc.identifier.pmid16940413-
dc.identifier.scopuseid_2-s2.0-33751105546en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33751105546&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume70en_US
dc.identifier.issue6en_US
dc.identifier.spage1946en_US
dc.identifier.epage1955en_US
dc.identifier.isiWOS:000242135700013-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLeung, CH=7402612570en_US
dc.identifier.scopusauthoridGrill, SP=7004975986en_US
dc.identifier.scopusauthoridLam, W=7203021943en_US
dc.identifier.scopusauthoridGao, W=7402758247en_US
dc.identifier.scopusauthoridSun, HD=7404828012en_US
dc.identifier.scopusauthoridCheng, YC=36041844200en_US
dc.identifier.issnl0026-895X-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats