Salicin, an extract from white willow bark, inhibits angiogenesis by blocking the ROS-ERK pathways

Phytother Res. 2014 Aug;28(8):1246-51. doi: 10.1002/ptr.5126. Epub 2014 Feb 17.


Salicin has been studied as a potent antiinflammatory agent. Angiogenesis is an essential process for tumor progression, and negative regulation of angiogenesis provides a good strategy for antitumor therapy. However, the potential medicinal value of salicin on antitumorigenic and antiangiogenic effects remain unexplored. In this study, we examined the antitumorigenic and antiangiogenic activity of salicin and its underlying mechanism of action. Salicin suppressed the angiogenic activity of endothelial cells, such as migration, tube formation, and sprouting from an aorta. Moreover, salicin reduced reactive oxygen species production and activation of the extracellular signal-regulated kinase pathway. The expression of vascular endothelial growth factor was also decreased by salicin in endothelial cells. When the salicin was administered to mice, salicin inhibited tumor growth and angiogenesis in a mouse tumor model. Taken together, salicin targets the signaling pathways mediated by reactive oxygen species and extracellular signal-regulated kinase, providing new perspectives into a potent therapeutic agent for hypervascularized tumors.

Keywords: ERK; ROS; angiogenesis; salicin; tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Aorta / drug effects
  • Benzyl Alcohols / pharmacology*
  • Cell Line, Tumor
  • Glucosides / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Humans
  • In Vitro Techniques
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Plant Bark / chemistry
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Salix / chemistry


  • Angiogenesis Inhibitors
  • Benzyl Alcohols
  • Glucosides
  • Reactive Oxygen Species
  • salicin