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Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway

Chung-Yu Ku1, Ying-Ren Wang1, Hsuan-Yuan Lin2

  • 1Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.

Plos One
|May 16, 2015
PubMed

Insights

Corosolic acid (CA) from Actinidia chinensis inhibits hepatocellular carcinoma (HCC) growth by targeting VEGFR2. CA shows synergistic effects with sorafenib, offering a potential therapeutic strategy for aggressive HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) treatment often involves targeting vascular endothelial growth factor receptor 2 (VEGFR2).
  • Identifying novel therapeutic agents for HCC is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the anti-cancer effects and molecular mechanisms of corosolic acid (CA) on HCC cells.
  • To evaluate CA's potential as a therapeutic or adjuvant strategy for HCC.

Main Methods:

  • In vitro kinase assays to assess CA's interaction with VEGFR2 ATP binding pocket.
  • Cellular assays to analyze the VEGFR2/Src/FAK/cdc42 signaling pathway and cell migration.
  • In vivo studies using a mouse model to evaluate CA's efficacy on tumor growth.
  • Combination studies with sorafenib to assess synergistic effects.

Main Results:

  • Corosolic acid (CA) directly inhibits VEGFR2 kinase activity.
  • CA down-regulates the VEGFR2/Src/FAK/cdc42 axis, reducing F-actin formation and cell migration in vitro.
  • CA demonstrated effective dose-dependent inhibition of tumor growth in vivo (5 mg/kg/day).
  • CA exhibited a synergistic effect with sorafenib across various concentrations.

Conclusions:

  • Corosolic acid (CA) possesses significant anti-cancer properties against HCC by inhibiting VEGFR2 signaling.
  • CA's ability to disrupt the VEGFR2/Src/FAK/cdc42 pathway and reduce tumor growth suggests its therapeutic potential.
  • CA may serve as a valuable therapeutic or adjuvant agent for patients with aggressive HCC, potentially in combination with existing treatments like sorafenib.

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