Effect of 3-Acetyloleanolic Acid Isolated from Cowpea Seeds (Vigna sinensis K.) on Angiopoietin-1-Induced Angiogenesis

Angiogenesis, a process leading to development of new blood vessels from pre-existing vessels, plays essential roles in embryonic development, wound healing, inflammation and tumor growth. Angiogenesis is critical in the development and dissemination of most human tumors. Natural compounds containing an anti-angiogenic activity are potentially important resources of tumor suppressive agents. Angiopoietin-1, a ligand for receptor tyrosine kinase Tie-2, plays an essential role in remodeling and maturation of blood vessels. In this work, we evaluated the effect of 3-acetyloleanolic acid, a pentacyclic triterpenoid isolated from cowpea seeds (Vigna sinensis K.), on angiopoietin-1-induced angiogenesis both in vitro and in vivo. 3-Acetyloleanolic acid inhibited proliferation, tube formation, and migration of human angiopoietin-1 (rhAngpt-1)-treated human umbilical vein endothelial cell (HUVEC). 3-Acetyloleanolic acid also reduced the activation of signaling factors such as focal adhesion kinase (FAK), ERK1/2 and AKT involved in angiopoietin-1/Tie-2 signaling pathway. The inhibitory effects of 3-acetyloleanolic acid on angiopoietin-1-induced angiogenesis were further determined in an angiopoietin-1-stimulated in vivo Matrigel plug assay and heterotropic CT-26 colon carcinoma animal (Balb/c mice) model. 3-Acetyloleanolic acid dramatically reduced the development of new blood vessels in angiopoietin-1-stimulated Matrigel plug. 3-Acetyloleanolic acid also reduced the volume and weight of heterotropic CT-26 colon carcinoma tumor. Taken together, these results indicate that 3-acetyloleanolic acid exhibits anti-angiogenic effects to inhibit angiopoietin-1-induced angiogenesis. This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2012R1A1B3001575).