Suppression of PMA-induced tumor cell invasion by capillarisin via the inhibition of NF-kappaB-dependent MMP-9 expression

Biochem Biophys Res Commun. 2008 Feb 22;366(4):1019-24. doi: 10.1016/j.bbrc.2007.12.068. Epub 2007 Dec 26.


Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of capillarisin, a bioactive flavonoid of Artemisia capillaries, on phorbol myristate acetate (PMA)-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Capillarisin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7 and the Matrigel invasion assay showed that capillarisin reduces PMA-induced invasion of MCF-7 cells. Capillarisin has been found to suppress PMA-induced MMP-9 expression through inhibition of the NF-kappaB-dependent transcriptional activity of MMP-9 gene via p38 MAPK and JNK signaling pathways. However, capillarisin had no effect on enzymatic activity of MMP-9 and expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2, the major endogenous inhibitors of MMPs. These results suggest that capillarisin represents a potential anti-metastatic agent suppressing cancer cell invasion through specific inhibition of NF-kappaB-dependent MMP-9 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromones / pharmacology*
  • Collagen / metabolism
  • Drug Combinations
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Laminin / metabolism
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B / antagonists & inhibitors*
  • Neoplasm Invasiveness
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Proteoglycans / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / genetics
  • Transcriptional Activation / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Chromones
  • Drug Combinations
  • Laminin
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Proteoglycans
  • Transcription Factor AP-1
  • matrigel
  • capillarisin
  • Collagen
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate