Pinostilbene Hydrate Suppresses Human Oral Cancer Cell Metastasis by Downregulation of Matrix Metalloproteinase-2 Through the Mitogen-Activated Protein Kinase Signaling Pathway

Cell Physiol Biochem. 2018;50(3):911-923. doi: 10.1159/000494476. Epub 2018 Oct 24.

Abstract

Background/aims: Cancer is the most common cause of death worldwide with approximately one third of people being diagnosed with cancer in their lifetime. Pinostilbene hydrate (PSH) A methylated derivative of resveratrol Has been reported to possess antioxidative Cardioprotective and anticancer properties. However the antimetastatic effect of pinostilbene in oral squamous cell carcinoma (OSCC) remains unknown.

Methods: In this study We investigated the effect of PSH on antimetastatic activity and the relevant signaling pathways underlying mechanisms of SCC-9 SAS and HSC-3 oral cancer cell lines by MTT assay Wound healing Transwell assay Zymography and western blot analysis.

Results: Our findings indicated that PSH inhibits migration and invasion ability by reducing the protein activity and expression of matrix metalloproteinases-2 (MMP-2) in all three cell lines. Moreover • The phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (p38) had significant inhibitory effects in the presence of PSH in the SCC9 and SAS cell lines. A combination of ERK1/2 and p38 inhibitors with PSH also reduced the migration and activity of MMP-2 in the SCC9 and SAS cell lines.

Conclusion: This study demonstrated that PSH suppresses MMP-2 enzymatic activity by downregulating the p38/ERK1/2 pathway and that it might be a promising agent for preventing OSCC cell metastasis.

Keywords: MAPK; MMP-2; Oral squamous cell carcinoma; Pinostilbene hydrate; migration.

MeSH terms

  • Butadienes / pharmacology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Down-Regulation / drug effects*
  • Humans
  • Imidazoles / pharmacology
  • Matrix Metalloproteinase 2 / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Nitriles / pharmacology
  • Pyridines / pharmacology
  • Signal Transduction / drug effects*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Butadienes
  • Imidazoles
  • Nitriles
  • Pyridines
  • Stilbenes
  • U 0126
  • pinostilbene
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • SB 203580