title: Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway.
abstract: Inhibition of VEGFR2 activity has been proposed as an important strategy for the clinical treatment of hepatocellular carcinoma (HCC). In this study, we identified corosolic acid (CA), which exists in the root of Actinidia chinensis, as having a significant anti-cancer effect on HCC cells. We found that CA inhibits VEGFR2 kinase activity by directly interacting with the ATP binding pocket. CA down-regulates the VEGFR2/Src/FAK/cdc42 axis, subsequently decreasing F-actin formation and migratory activity in vitro. In an in vivo model, CA exhibited an effective dose (5 mg/kg/day) on tumor growth. We further demonstrate that CA has a synergistic effect with sorafenib within a wide range of concentrations. In conclusion, this research elucidates the effects and molecular mechanism for CA on HCC cells and suggests that CA could be a therapeutic or adjuvant strategy for patients with aggressive HCC.
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Ku
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
authors.forename: Ying-Ren
authors.initials: YR
authors.lastname: Wang
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan; Department of Life Science, National Taiwan Normal University, Taipei, 116, Taiwan.
authors.forename: Hsuan-Yuan
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Lu
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan; Department of Life Science, National Taiwan Normal University, Taipei, 116, Taiwan.
authors.forename: Jung-Yaw
authors.initials: JY
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000077157:Sorafenib; D014315:Triterpenes / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D014315:Triterpenes; D009536:Niacinamide; D000255:Adenosine Triphosphate; D000077157:Sorafenib; C113861:corosolic acid; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases