Effect of beta-escin sodium on endothelial cells proliferation, migration and apoptosis.
beta-Escin, the major active compound in extracts of the horse chestnut Aesculus hippocastanum seed, has shown clinically significant activity in chronic venous insufficiency (CVI). Our previous studies had shown that beta-escin sodium inhibited angiogenesis in chick chorioallantoic membrane (CAM) and in aortic disk assay. In this study, we explored the direct effect of beta-escin sodium on proliferation, migration and apoptosis in human umbilical vein endothelial cells (HUVECs) and ECV304 cells. Sulforhodamine B (SRB) assay showed that beta-escin sodium (10, 20, 40 microg/ml) inhibited endothelial cells (ECs) proliferation dose-dependently. beta-escin sodium also induced ECs apoptosis at 40 microg/ml. Cell migration was evaluated by an improved wound assay: barren spot assay. And the direct effect on cell motility excluding influence of cell proliferation was examined by High Content Screening (HCS, Cellomics) assay. The data indicated that beta-escin sodium suppressed ECs migration and cell motility. Western blot results suggested that beta-escin sodium acts on ECs possibly by increasing expression of thrombospondin-1 (TSP-1), and decreasing expression of PKC-alpha and activation of p44/42 mitogen-activated protein kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK). Our findings give the evidence that beta-escin sodium might have potential anti-angiogenic activity via its direct effects on ECs.
Wang
Xu-Hua
XH
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University 100083, Beijing China.
Xu
Bo
B
Liu
Jing-Tao
JT
Cui
Jing-Rong
JR
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004928:Escin / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D012503:Saponins; D019700:Thrombospondin 1; D004928:Escin; D051571:Protein Kinase C-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases