Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells

J Ethnopharmacol. 2009 Nov 12;126(2):252-7. doi: 10.1016/j.jep.2009.08.032. Epub 2009 Aug 26.


Ethnopharmacological relevance: The expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) are pivotal steps in breast cancer pathogenesis. In a previous study, we reported that silibinin suppresses TPA-induced MMP-9 expression through the Raf/MEK/ERK pathway.

Aims of the study: Herein we determined the co-relationship between MMP-9 and COX-2, as well as the effect of silibinin on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and COX-2 expression in the human breast cancer cells, MCF-7 and MDA-MB231.

Methods: The toxicity of silibinin was evaluated by Quick Cell Proliferation Assay Kit II. MMP-9 and COX-2 expression were analyzed by Zymography and Western blotting, respectively. Adenoviral constitutively active (CA)-MEK was used to activate MEK/ERK pathway.

Results: The expression of MMP-9 and COX-2 in response to TPA was increased, whereas TPA-induced MMP-9 and COX-2 expression was decreased by silibinin. Our results showed that TPA-induced MMP-9 expression was inhibited by celecoxib in a dose-dependent fashion, but not MMP-1-expression. Both MMP-9 and COX-2 expression were significantly increased by CA-MEK overexpression. In contrast, TPA-induced MMP-9 and COX-2 expression was decreased by UO126 (MEK 1/2 inhibitor).

Conclusion: Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Butadienes / pharmacology
  • Celecoxib
  • Cell Line, Tumor
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation
  • Humans
  • MAP Kinase Kinase Kinases / metabolism
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 9 / metabolism*
  • Milk Thistle / chemistry*
  • Nitriles / pharmacology
  • Phytotherapy
  • Protein Kinase Inhibitors / pharmacology
  • Pyrazoles / pharmacology
  • Seeds
  • Silybin
  • Silymarin / pharmacology
  • Silymarin / therapeutic use
  • Sulfonamides / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Butadienes
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Silymarin
  • Sulfonamides
  • U 0126
  • Silybin
  • Cyclooxygenase 2
  • MAP Kinase Kinase Kinases
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1
  • Celecoxib
  • Tetradecanoylphorbol Acetate