Norcantharidin Suppresses YD-15 Cell Invasion Through Inhibition of FAK/Paxillin and F-Actin Reorganization

Molecules. 2019 May 19;24(10):1928. doi: 10.3390/molecules24101928.

Abstract

Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit activity against various types of cancers. However, the anti-invasive effects of NCTD and its molecular mechanism in human mucoepidermoid carcinoma (MEC) remain incompletely elucidated. Clonogenic, wound healing, invasion, zymography, western blotting and immunocytochemistry assays were performed in YD-15 cells to investigate the anti-invasive effect of NCTD and its molecular mechanism of action. The inhibitory effects of NCTD on invasiveness were compared with those of a novel focal adhesion kinase (FAK) kinase inhibitor, PF-562271. NCTD markedly suppressed the colony formation, migration, and invasion of YD-15 cells as well as the activities of MMP-2 and MMP-9. It disrupted F-actin reorganization through suppressing the FAK/Paxillin axis. Moreover, NCTD exhibited a powerful anti-invasive effect compared with that of PF-562271 in YD-15 cells. Collectively, these results suggest that NCTD has a potential anti-invasive activity against YD-15 cells. This study may clarify the impact of NCTD on migration and invasion of human MEC cells.

Keywords: F-actin reorganization; focal adhesion kinase; invasion; mucoepidermoid carcinoma; norcantharidin; paxillin.

MeSH terms

  • Actins / antagonists & inhibitors*
  • Antineoplastic Agents / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Carcinoma, Mucoepidermoid / drug therapy
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Paxillin / antagonists & inhibitors*
  • Signal Transduction

Substances

  • Actins
  • Antineoplastic Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Matrix Metalloproteinase Inhibitors
  • Paxillin
  • norcantharidin
  • Focal Adhesion Protein-Tyrosine Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9