title: Gleditsioside B, a triterpene saponin isolated from the anomalous fruits of Gleditsia sinensis Lam., abrogates bFGF-induced endothelial cell migration through preventing the activation of MMP-2 and FAK via inhibiting ERK and PI3K/AKT signaling pathways.
abstract: Angiogenesis has become an attractive target for the treatment of certain diseases such as cancer and rheumatoid arthritis. Our previous studies demonstrated that the saponin fraction from Gleditsia sinensis fruits had anti-angiogenic potential, and Gleditsiosides B (GB) was probably the main active constituent. In the present study, we assessed the effect of GB on endothelial cell migration, a crucial event in angiogenesis, and explored the underlying mechanisms. The migration of endothelial cells was assessed by transwell. The expressions of MMP-2/-9 and TIMP-1/-2 were analyzed by Western blotting, and the activities of MMP-2/-9 were detected by gelatin zymography assay. Moreover, migration-related proteins and signaling pathways, including FAK, MAPKs and PI3K/AKT, were analyzed by Western blotting. It was shown that GB, at a concentration of 10 μM without significant cytotoxicity, could effectively abrogate the migration of human umbilical vein endothelial cells (HUVECs) induced by bFGF. GB also inhibited the expression and activity of MMP-2, elevated the expression of TIMP-1, and restrained the phosphorylations of FAK, ERK, PI3K and AKT in a concentration-dependent manner. The findings suggest that GB was able to abrogate the migration of endothelial cells through down-regulating the activation of MMP-2 and FAK via preventing ERK and PI3K/AKT signaling pathways.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Tong
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Wei
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xia
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005638:Fruit; D005786:Gene Expression Regulation / Q000187:drug effects; D031501:Gleditsia / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D012503:Saponins; C581613:gleditsioside B; D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2