title: Corosolic Acid Exhibits Anti-angiogenic and Anti-lymphangiogenic Effects on In Vitro Endothelial Cells and on an In Vivo CT-26 Colon Carcinoma Animal Model.
abstract: We describe the anti-angiogenic and anti-lymphangiogenic effects of corosolic acid, a pentacyclic triterpenoid isolated from Cornus kousa Burg. A mouse colon carcinoma CT-26 animal model was employed to determine the in vivo anti-angiogenic and anti-lymphangiogenic effects of corosolic acid. Corosolic acid induced apoptosis in CT-26 cells, mediated by the activation of caspase-3. In addition, it reduced the final tumor volume and the blood and lymphatic vessel densities of tumors, indicating that it suppresses in vivo angiogenesis and lymphangiogenesis. Corosolic acid inhibited the proliferation and tube formation of human umbilical vein endothelial cells and human dermal lymphatic microvascular endothelial cells. In addition, corosolic acid decreased the proliferation and migration of human umbilical vein endothelial cells stimulated by angiopoietin-1. Pretreatment with corosolic acid decreased the phosphorylation of focal adhesion kinase (FAK) and ERK1/2, suggesting that corosolic acid contains anti-angiogenic activity that can suppress FAK signaling induced by angiopoietin-1.
authors: Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
authors: Ki Hyun
authors: KH
authors: Yoo
authors: Jong-Hwa
authors: JH
authors: Park
authors: Dae Young
authors: DY
authors: Lee
authors: Jeon
authors: J
authors: Hwang-Bo
authors: Nam In
authors: NI
authors: Baek
authors: In Sik
authors: IS
authors: Chung
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D042683:Angiopoietin-1; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy*; D042783:Endothelial Cells / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009389:Neovascularization, Pathologic; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D014315:Triterpenes; C113861:corosolic acid; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: angiogenesis; angiopoietin-1; colon carcinoma CT-26; corosolic acid; lymphangiogenesis