title: The dineolignan from Saururus chinensis, manassantin B, inhibits tumor-induced angiogenesis via downregulation of matrix metalloproteinases 9 in human endothelial cells.
abstract: Manassantin B (MB) is a neolignan isolated from Saururus chinensis that exhibits a range of activities, including anti-inflammatory, antiseptic and antitumor activity. MB was recently found to affect cell adhesion and expression of several adhesion molecules. Based on the important roles of these adhesion molecules in angiogenesis, we evaluated a possible role for MB in tumor-induced angiogenesis in endothelial cells (ECs). In the present study, we found that MB blocked tumor-induced tube formation of ECs and significantly inhibited the invasion of ECs through the reconstituted basement membrane. MB suppressed the activity of matrix metalloproteinases (MMPs) and downregulated the expression of matrix metalloproteinases 9. Western blotting showed reduction of RUNX2 activation by MB. RUNX2 transcription factor assay and chromatin immunoprecipitation assay showed that the interaction between RUNX2 and target sequences in the matrix metalloproteinases 9 promoters was inhibited by MB. Our findings suggested that the inhibitory effects of MB on tumor-induced angiogenesis were caused by matrix metalloproteinases 9 inhibition, which was associated with the downregulation of RUNX2 transcriptional activity.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China.
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Network and Educational Technology Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China.
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Fu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D005663:Furans / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D032134:Saururaceae / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D050659:Core Binding Factor Alpha 1 Subunit; D005663:Furans; C482885:manassantin B; D020780:Matrix Metalloproteinase 9