Wogonin Suppresses the Activity of Matrix Metalloproteinase-9 and Inhibits Migration and Invasion in Human Hepatocellular Carcinoma

Molecules. 2018 Feb 11;23(2):384. doi: 10.3390/molecules23020384.

Abstract

As one of the major active ingredients in Radix Scutellariae, wogonin has been shown to be associated with various pharmacological activities on cancer cell growth, apoptosis, and cell invasion and migration. Here, we demonstrated that wogonin may harbor potential anti-metastatic activities in hepatocarcinoma (HCC). The anti-metastasis potential of wogonin and its underlying mechanisms were evaluated by ligand-protein docking approach, surface plasmon resonance assay, and in vitro gelatin zymography studies. Our results showed that wogonin (100 μM, 50 μM) suppressed MHCC97L and PLC/PRF/5 cells migration and invasion in vitro. The docking approach and surface plasmon resonance assay indicated that the potential binding affinity between wogonin and matrix metalloproteinase-9 (MMP-9) may lead to inhibition of MMP-9 activity and further leads to suppression of tumor metastasis. This conclusion was further verified by Western blot results and gelatin zymography analysis. Wogonin might be a potent treatment option for disrupting the tumor metastasis that favors HCC development. The potential active targets from computational screening integrated with biomedical study may help us to explore the molecular mechanism of herbal medicines.

Keywords: cancer migration and invasion; hepatocarcinoma; matrix metalloproteinase-9; wogonin.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Binding Sites
  • Cell Line, Tumor
  • Cell Migration Assays
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Flavanones / chemistry
  • Flavanones / pharmacology*
  • Gene Expression Regulation, Neoplastic*
  • Hepatocytes / drug effects*
  • Hepatocytes / enzymology
  • Hepatocytes / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Molecular Docking Simulation
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Scutellaria baicalensis / chemistry*
  • Signal Transduction
  • Stromal Interaction Molecule 1 / antagonists & inhibitors
  • Stromal Interaction Molecule 1 / genetics
  • Stromal Interaction Molecule 1 / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Flavanones
  • Neoplasm Proteins
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Intercellular Adhesion Molecule-1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • wogonin