7-Chloroarctinone-b as a new selective PPARγ antagonist potently blocks adipocyte differentiation

	7-Chloroarctinone-b as a new selective PPARγ antagonist potently blocks adipocyte differentiation
	Yongtao LI 1; Li LI 1; Jing CHEN 2; Tiancen HU 2; Jin HUANG 1; Yuewei GUO 2; Hualiang JIANG 1; Xu SHEN 1
刊名	Acta Pharmacologica Sinica
	2009
卷号	30 期号:9 页码:1351
关键词	peroxisome proliferator-activated receptor antagonist surface plasmon resonance recruitment of the coactivator adipocyte differentiation
ISSN号	1671-4083
英文摘要	Aim: Peroxisome proliferator-activated receptor gamma (PPARy) is a therapeutic target for obesity, cancer and diabetes mellitus. In order to develop potent lead compounds for obesity treatment, we screened a natural product library for novel PPARy antagonists with inhibitory effects on adipocyte differentiation. Methods: Surface plasmon resonance (SPR) technology and cell-based transactivation assay were used to screen for PPARy antago-nists. To investigate the antagonistic mechanism of the active compound, we measured its effect on PPARy/RXRα heterodimerization and PPARy co-activator recruitment using yeast two-hybrid assay, Gal4/UAS cell-based assay and SPR based assay. The 3T3-L1 cell differentiation assay was used to evaluate the effect of the active compound on adipocyte differentiation. Results: A new thiophene-acetylene type of natural product, 7-chloroarctinone-b (CAB), isolated from the roots of Rhaponticum uniflo-rum, was discovered as a novel PPARγ antagonist capable of inhibiting rosiglitazone-induced PPARγ transcriptional activity. SPR analy-sis suggested that CAB bound tightly to PPARγ and considerably antagonized the potent PPARy agonist rosigtitazone-stimulated PPARγ-LBD/RXRα-LBD binding. Gal4/UAS and yeast two-hybrid assays were used to evaluate the antagonistic activity of CAB on rosiglitazone-induced recruitment of the coactivator for PPARy. CAB could efficiently antagonize both hormone and rosiglitazone-induced adipocyte differentiation in cell culture. Conclusion: CAB shows antagonistic activity to PPARγ and can block the adipocyte differentiation, indicating it may be of potential use as a lead therapeutic compound for obesity.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/293907]
专题	中国科学院上海药物研究所
作者单位	1.华东理工大学 2.中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Yongtao LI,Li LI,Jing CHEN,et al. 7-Chloroarctinone-b as a new selective PPARγ antagonist potently blocks adipocyte differentiation[J]. Acta Pharmacologica Sinica,2009,30(9):1351.
APA	Yongtao LI.,Li LI.,Jing CHEN.,Tiancen HU.,Jin HUANG.,...&Xu SHEN.(2009).7-Chloroarctinone-b as a new selective PPARγ antagonist potently blocks adipocyte differentiation.Acta Pharmacologica Sinica,30(9),1351.
MLA	Yongtao LI,et al."7-Chloroarctinone-b as a new selective PPARγ antagonist potently blocks adipocyte differentiation".Acta Pharmacologica Sinica 30.9(2009):1351.