Hypericin in the dark inhibits key steps of angiogenesis in vitro

Eur J Pharmacol. 2005 Jun 1;516(2):97-103. doi: 10.1016/j.ejphar.2005.03.047.


Photoactivated hypericin has a potent cytotoxic effect over a wide range of cells. However, very recently hypericin has been shown to have antitumoral and antimetastatic effects in the dark. The aim of this study was to test whether hypericin in the dark affects angiogenesis. Different in vitro assays were used to study the potential effects of this compound on key steps of angiogenesis, namely, a colorimetric assay of cell proliferation/viability, a tubular formation on Matrigel assay, zymographic assays for gelatinases and urokinase, a wound assay for migration and a fluorometric assay for invasion through Matrigel. In this report, we show for the first time that hypericin kept in the dark inhibits several key steps of the angiogenic process, namely, bovine endothelial cell proliferation, formation of tubular-like structures on Matrigel, migration and invasion, as well as extracellular matrix degrading urokinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Capillaries / cytology
  • Capillaries / drug effects
  • Capillaries / growth & development
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen
  • Darkness*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Laminin
  • Matrix Metalloproteinase 2 / metabolism
  • Perylene / analogs & derivatives*
  • Perylene / pharmacology*
  • Proteoglycans
  • Radiation-Sensitizing Agents / pharmacology
  • Time Factors
  • Urokinase-Type Plasminogen Activator / metabolism


  • Angiogenesis Inhibitors
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • Radiation-Sensitizing Agents
  • matrigel
  • Perylene
  • hypericin
  • Collagen
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2