Corosolic acid inhibits hepatocellular carcinoma cell migration by targeting the VEGFR2/Src/FAK pathway
Journal
PLoS ONE
Journal Volume
10
Journal Issue
5
Date Issued
2015
Author(s)
Ku C.-Y.
Wang Y.-R.
Lin H.-Y.
SHAO-CHUN LU
Lin J.-Y.
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. ? 2015 Ku et al.
SDGs
Other Subjects
Actinidia chinensis extract; adenosine triphosphate; corosolic acid; dimethyl sulfoxide; F actin; focal adhesion kinase; natural product; plant extract; protein Cdc42; protein tyrosine kinase; small interfering RNA; sorafenib; unclassified drug; ursolic acid; vasculotropin receptor 2; actin; antineoplastic agent; carbanilamide derivative; corosolic acid; focal adhesion kinase 1; KDR protein, human; nicotinamide; protein tyrosine kinase; PTK2 protein, human; sorafenib; triterpene; vasculotropin receptor 2; Actinidia chinensis; animal experiment; animal model; animal tissue; antineoplastic activity; Article; cancer adjuvant therapy; cancer cell; cancer patient; cancer therapy; cell migration; controlled study; down regulation; drug effect; drug mechanism; drug potentiation; drug structure; human; human cell; in vitro study; in vivo study; liver cell carcinoma; male; mouse; nonhuman; plant root; tumor growth; analogs and derivatives; Carcinoma, Hepatocellular; cell motion; drug effects; genetics; Hep-G2 cell line; Liver Neoplasms; metabolism; pathology; signal transduction; tumor cell line; Actinidia chinensis; Actins; Adenosine Triphosphate; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Down-Regulation; Drug Synergism; Focal Adhesion Kinase 1; Hep G2 Cells; Humans; Liver Neoplasms; Niacinamide; Phenylurea Compounds; Signal Transduction; src-Family Kinases; Triterpenes; Vascular Endothelial Growth Factor Receptor-2
Publisher
Public Library of Science
Type
journal article