Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells

Biochem Biophys Res Commun. 2007 Mar 2;354(1):165-71. doi: 10.1016/j.bbrc.2006.12.181. Epub 2007 Jan 2.


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 silibinin, a flavonoid antioxidant from milk thistle (Silybum marianum L.) on PMA-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Silibinin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7. Silibinin has been found to inhibit PMA-induced MMP-9 gene transcriptional activity by blocking the activation of AP-1 via MAPK signaling pathways. Moreover, the Matrigel invasion assay showed that silibinin reduces PMA-induced invasion of MCF-7 cells. These results suggest that silibinin represents a potential anti-metastatic agent suppressing PMA-induced cancer cell invasion through the specific inhibition of AP-1-dependent MMP-9 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 9 / metabolism*
  • Silybin
  • Silymarin / administration & dosage
  • Tetradecanoylphorbol Acetate / administration & dosage*
  • Transcription Factor AP-1 / metabolism*
  • Transcriptional Activation / drug effects*


  • Drug Combinations
  • Silymarin
  • Transcription Factor AP-1
  • Silybin
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate