Antiangiogenic Potential of Three Triterpenic Acids in Human Liver Cancer Cells

• Published in: Journal of agricultural and food chemistry 2011-01, Vol.59 (2), p.755-762
• Main Authors: Lin, Chun-Che, Huang, Chun-Yin, Mong, Mei-Chin, Chan, Chien-Yi, Yin, Mei-Chin
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Biological and medical sciences; Cell Line, Tumor; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Food industries; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Interleukin-8 - genetics; Interleukin-8 - metabolism; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Molecular Nutrition; Oleanolic Acid - pharmacology; Triterpenes - pharmacology; Ursolic Acid
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf103904b

Three triterpenic acids, oleanolic acid, ursolic acid and maslinic acid, at 2 or 4 μmol/L were used to study their antiangiogenic potential in human liver cancer Hep3B, Huh7 and HA22T cell lines. The effects of these compounds upon the level and/or expression of hypoxia-inducible factor (HIF)-1α, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), interleukin (IL)-8, urokinase plasminogen activator (uPA), reactive oxygen species (ROS), nitric oxide (NO) and cell invasion and migration were examined. Results showed that these triterpenic acids at 4 μmol/L significantly suppressed HIF-1α expression in three cell lines (P < 0.05); and these compounds at test doses failed to affect bFGF expression (P > 0.05). Three triterpenic acids dose-dependently decreased production and expression of VEGF and IL-8, retained glutathione level, lowered ROS and NO levels, and declined cell invasion and migration in test cell lines (P < 0.05). These compounds also dose-dependently reduced uPA production and expression in Hep3B and Huh7 cell lines (P < 0.05); but these agents only at 4 μmol/L significantly suppressed uPA production and expression in HA22T cells (P < 0.05). These findings suggest that these triterpenic acids are potent antiangiogenic agents to retard invasion and migration in liver cancer cells.