Fisetin inhibits matrix metalloproteinases and reduces tumor cell invasiveness and endothelial cell tube formation

Nutr Cancer. 2013;65(8):1192-9. doi: 10.1080/01635581.2013.828090. Epub 2013 Oct 7.


Matrix metalloproteinases (MMPs) play an important role in tissue remodeling during normal physiological situations and pathological implications such as tumor invasion and metastasis. MMP inhibitors were screened from extracts of medicinal herbs by an enzymatic assay using the MMP-14 catalytic domain. Among samples tested, a methanol extract of the root of Dalbergia odorifera T. CHEN (Leguminosae) showed the strongest inhibitory activity. The inhibitory component was purified through fractionation methods and identified as fisetin, abundant in many fruits and vegetables. In addition to inhibition of MMP-14, fisetin inhibits MMP-1, MMP-3, MMP-7, and MMP-9, more efficiently than a naturally occurring MMP inhibitor tetracycline. Fisetin dose-dependently inhibits proliferation of fibrosarcoma HT-1080 cells and human umbilical vascular endothelial cells (HUVECs), MMP-14-mediated activation of proMMP-2 in HT-1080 cells, invasiveness of HT-1080 cells, and in vitro tube formation of HUVECs. Therefore, fisetin could be valuable as a chemopreventive agent against cancer and a lead compound for development of therapeutic MMP inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins E / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemoprevention
  • Dalbergia / chemistry
  • Dose-Response Relationship, Drug
  • Enzyme Precursors / genetics
  • Enzyme Precursors / metabolism
  • Flavonoids / pharmacology*
  • Flavonols
  • Gelatinases / genetics
  • Gelatinases / metabolism
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Matrix Metalloproteinases / metabolism*
  • Neoplasm Invasiveness
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry


  • Apolipoproteins E
  • Enzyme Precursors
  • Flavonoids
  • Flavonols
  • Matrix Metalloproteinase Inhibitors
  • Plant Extracts
  • Gelatinases
  • Matrix Metalloproteinases
  • progelatinase
  • fisetin