3‐O‐Acetyloleanolic acid inhibits angiopoietin‐1‐induced angiogenesis and lymphangiogenesis via suppression of angiopoietin‐1/Tie‐2 signaling

• Published in: Phytotherapy research 2020-02, Vol.34 (2), p.359-367
• Main Authors: Hwang‐Bo, Jeon, Park, Jong‐Hwa, Chung, In Sik
• Format: Article
• Language: English
• Subjects: 3‐O‐acetyloleanolic acid; Activation; AKT protein; Angiogenesis; Angiogenesis Inhibitors - pharmacology; Angiopoietin; Angiopoietin-1 - metabolism; angiopoietin‐1; Animal models; Animals; Apoptosis - drug effects; Cell Line, Tumor; Cell proliferation; Colon; CT‐26 allograft animal model; Endothelial cells; Female; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Hypoxia; lymphangiogenesis; Lymphangiogenesis - drug effects; Metastases; Mice; Mice, Inbred BALB C; Microvasculature; Neoplasms, Experimental - drug therapy; Neovascularization, Pathologic - drug therapy; Plugs; Receptor, TIE-2 - metabolism; Signal transduction; Signal Transduction - drug effects; Signaling; Tie‐2; Triterpenes - pharmacology; Tumors; Umbilical vein
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6526

Tumor angiogenesis and lymphangiogenesis are important processes in tumor progression and metastasis. The inhibitory effects of 3‐O‐acetyloleanolic acid (3AOA), a pentacyclic triterpenoid compound isolated from Vigna sinensis K., on tumor‐induced angiogenesis and lymphangiogenesis in vitro and in vivo were studied. Angiopoietin‐1 is an important angiogenic and lymphangiogenic factor secreted from colon carcinoma CT‐26 cells under hypoxia conditions. 3AOA inhibited proliferation, migration, and tube formation of angiopoietin‐1‐treated human umbilical vein endothelial cells (HUVEC) and human lymphatic microvascular endothelial cells (HLMEC). 3AOA reduced angiogenesis and lymphangiogenesis in angiopoietin‐1‐stimulated Matrigel plugs. Also, 3AOA inhibited tumor growth and tumor‐induced angiogenesis and lymphangiogenesis in an angiopoietin‐1‐induced CT‐26 allograft colon carcinoma animal model. 3AOA inhibited activation of the angiopoietin‐1 receptor Tie‐2 and activation of the downstream signaling factors FAK, AKT, and ERK1/2 that are involved in the angiopoietin‐1/Tie‐2‐signaling pathway. Thus, 3AOA has an inhibitory effect on angiogenesis and lymphangiogenesis induced by angiopoietin‐1 both in vitro and in vivo, and the inhibitory effect of 3AOA is probably due to suppression of angiopoietin‐1/Tie‐2 signaling in HUVEC and HLMEC.