Eriocalyxin B inhibits nuclear factor-kappa B activation by interfering with the binding of both p65 and p50 to the response element in a noncompetitive manner
Leung, Chung-Hang; Grill, Susan P.; Lam, Wing; Gao, Wenli; Sun, Han-Dong; Cheng, Yung-Chi
2006-12-01
Source PublicationMOLECULAR PHARMACOLOGY
Volume70Issue:6Pages:1946-1955
AbstractNuclear factor-kappa B (NF-kappa B) 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-kappa B inhibitor, eriocalyxin B (Eri-B), an ent-kauranoid isolated from Isodon eriocalyx, an anti-inflammatory remedy. The presence of two alpha,beta-unsaturated ketones give this compound the uniqueness among the ent-kauranoids tested. Eri-B inhibited the NF-kappa B transcriptional activity but not that of cAMP response element-binding protein. It suppressed the transcription of NF-kappa B downstream gene products including cyclooxygenase-2 and inducible nitric-oxide synthase induced by tumor necrosis factor-alpha or lipopolysaccharide in macrophages and hepatocarcinoma cells. Chromatin immunoprecipitation assay indicated that Eri-B selectively blocked the binding between NF-kappa B 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-kappa B inhibitor that could be potentially used for the treatment of a variety of NF-kappa B-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.
DOI10.1124/mol.106.028480
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000242135700013
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/24799
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming, Peoples R China
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Leung, Chung-Hang,Grill, Susan P.,Lam, Wing,et al. Eriocalyxin B inhibits nuclear factor-kappa B activation by interfering with the binding of both p65 and p50 to the response element in a noncompetitive manner[J]. MOLECULAR PHARMACOLOGY,2006,70(6):1946-1955.
APA Leung, Chung-Hang,Grill, Susan P.,Lam, Wing,Gao, Wenli,Sun, Han-Dong,&Cheng, Yung-Chi.(2006).Eriocalyxin B inhibits nuclear factor-kappa B activation by interfering with the binding of both p65 and p50 to the response element in a noncompetitive manner.MOLECULAR PHARMACOLOGY,70(6),1946-1955.
MLA Leung, Chung-Hang,et al."Eriocalyxin B inhibits nuclear factor-kappa B activation by interfering with the binding of both p65 and p50 to the response element in a noncompetitive manner".MOLECULAR PHARMACOLOGY 70.6(2006):1946-1955.
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