Caffeic acid phenyl ester in propolis is a strong inhibitor of matrix metalloproteinase-9 and invasion inhibitor: isolation and identification

Clin Chim Acta. 2005 Dec;362(1-2):57-64. doi: 10.1016/j.cccn.2005.05.009. Epub 2005 Jul 6.

Abstract

Background: Propolis has been used as a folk medicine and has several proven biological activities. Herbal remedies recommended for cancer therapies in Korea.

Methods: Matrix metalloproteinase (MMP)-9-inhibitory activity of propolis has been assessed. CAPE as an acting compound was isolated and molecular structure was determined. Anti-invasion activity of CAPE was assayed using hepatocarcinoma cells.

Results: Propolis ethanol extracts showed a strong inhibitory effect of MMP-9 activity, which is known to be involved in tumor cell invasion and metastasis in a concentration-dependent manner on zymography. Assay guided fractionation led to the isolation of a caffeic acid phenyl ester (CAPE) as the compound responsible for the anti-MMP-9 activity. CAPE was obtained by reversed-phase HPLC, and its structure was elucidated by fast atom bombardment mass spectrometry and tandem mass spectrometry. The purified CAPE inhibited MMP-9 activity with the IC(50) of 1.0-2.0 nmol/l.

Conclusions: CAPE possesses selective antiproliferative activity toward hepatocaricoma cell line Hep3B, but not primary cultured mouse hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeic Acids / chemistry
  • Caffeic Acids / isolation & purification*
  • Caffeic Acids / pharmacology*
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Mice
  • Molecular Structure
  • Neoplasm Invasiveness / pathology
  • Phenylethyl Alcohol / analogs & derivatives
  • Propolis / chemistry*

Substances

  • Caffeic Acids
  • Matrix Metalloproteinase Inhibitors
  • Propolis
  • Matrix Metalloproteinase 9
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol