Resveratrol inhibits tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells

Biomed Pharmacother. 2008 Jul-Aug;62(6):366-72. doi: 10.1016/j.biopha.2007.09.006. Epub 2007 Oct 22.

Abstract

Resveratrol is an active polyphenol found in red wine that has anti-cancer effects, but the molecular mechanisms of resveratrol on tumor invasion inhibition have not been well documented. The aim of this study was to elucidate the effects of resveratrol on invasion ability of human hepatocellular carcinoma cells and TNF-alpha-mediated MMP-9 expression. The expression activity of MMP-9 was measured by zymography, RT-PCR and western blot analysis. The expression of NF-kappa B was measured by EMSA and western blot analysis. TNF-alpha induced the MMP-9 expression in HepG2 cells. Resveratrol significantly inhibited TNF-alpha-mediated MMP-9 expression in HepG2 cells. NF-kappa B inhibitor induced a marked reduction in MMP-9 expression, and it suggested that NF-kappa B could play an important role in TNF-alpha-mediated MMP-9 expression. Furthermore, resveratrol significantly suppressed TNF-alpha-mediated NF-kappa B expression and invasion of HepG2 cells. Our results showed that resveratrol inhibited TNF-alpha-mediated MMP-9 expression and invasion of human hepatocellular carcinoma cells. The inhibitory effects are partly associated with the downregulation of the NF-kappa B signaling pathway.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • NF-kappa B
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 9
  • Resveratrol