Stereospecific induction of nuclear factor-kappa B activation by isochamaejasmin

doi:10.1124/mol.105.014720

	Stereospecific induction of nuclear factor-kappa B activation by isochamaejasmin
	Tian, QH ; Li, J ; Xie, X; Sun, ML ; Sang, HR ; Zhou, CH ; An, TY ; Hu, LH ; Ye, RD ; Wang, MW
刊名	MOLECULAR PHARMACOLOGY
	2005-12
卷号	68 期号:6 页码:1534-1542
ISSN号	0026-895X
DOI	10.1124/mol.105.014720
文献子类	Article
英文摘要	The root of Stellera chamaejasme L. is a traditional Chinese herb termed Rui Xiang Lang Du and has been used to treat solid tumors, tuberculosis and psoriasis. Exactly how S. chamaejasme L. regulates cellular responses remains unclear. We examined four biflavonoids isolated from S. chamaejasme L., including isochamaejasmin, two of its stereo-isomers and a methyl derivative, in functional assays originally designed to screen ligands for the G protein-coupled formyl peptide receptor-like 1 (FPRL1). Isochamaejasmin was found to induce the expression of a nuclear factor (NF)-kappa B-directed reporter gene in transfected HeLa cells with an EC(50) of 3.23 mu M, independently of FPRL1. The isochamaejasmin-stimulated NF-kappa B reporter activity was accompanied by nuclear translocation of NF-kappa B proteins and was blocked by a dominant-negative construct of I kappa B alpha. Isochamaejasmin also induced time-dependent phosphorylation of the mitogen-activated protein kinases extracellular signal-regulated kinase 1/2 and p38, and a novel protein kinase C (PKC delta). Likewise, inhibition of these kinases with the respective pharmacological inhibitors significantly reduced the isochamaejasmin-stimulated NF-kappa B activation. It is noteworthy that the two stereoisomers and the methyl derivative did not induce detectable activation of NF-kappa B and were more cytotoxic than isochamaejasmin, which could partially rescue cycloheximide-induced apoptosis. Inhibition of NF-kappa B activation reversed the anti-apoptotic effect of isochamaejasmin. These results provide the first evidence for a potential mechanism of action by S. chamaejasme L., and indicate that structurally similar compounds derived from S. chamaejasme L. may have different pharmacological properties.
资助项目	NIAID NIH HHS[AI040176]
WOS关键词	STELLERA-CHAMAEJASME L ; FORMYL PEPTIDE RECEPTOR ; TUMOR PROMOTER ; 7-TRANSMEMBRANE ; INFLAMMATION ; GNIDIMACRIN ; MECHANISM ; LIGAND
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000233340200004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273764]
专题	中国科学院上海药物研究所
通讯作者	Wang, MW
作者单位	1.Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Tian, QH,Li, J,Xie, X,et al. Stereospecific induction of nuclear factor-kappa B activation by isochamaejasmin[J]. MOLECULAR PHARMACOLOGY,2005,68(6):1534-1542.
APA	Tian, QH.,Li, J.,Xie, X.,Sun, ML.,Sang, HR.,...&Wang, MW.(2005).Stereospecific induction of nuclear factor-kappa B activation by isochamaejasmin.MOLECULAR PHARMACOLOGY,68(6),1534-1542.
MLA	Tian, QH,et al."Stereospecific induction of nuclear factor-kappa B activation by isochamaejasmin".MOLECULAR PHARMACOLOGY 68.6(2005):1534-1542.