Inducible nitric oxide synthase-vascular endothelial growth factor axis: a potential target to inhibit tumor angiogenesis by dietary agents

Curr Cancer Drug Targets. 2007 Aug;7(5):475-83. doi: 10.2174/156800907781386632.


Human solid tumors remain latent in the absence of angiogenesis since it is a critical process for their further growth and progression. Experimental evidence suggests that targeting tumor angiogenesis may be a novel strategy to check tumor growth and metastases. Recent studies suggest that several bioactive food components can suppress tumor growth by inhibiting angiogenesis. This suppression occurs because of a direct effect on the tumor, as well as a direct effect on vascular endothelial cells. These food components can target epigenetic processes and thereby suppress the pro-angiogenic tumor microenvironment. One likely epigenetic target is inducible nitric oxide synthase (iNOS). iNOS is known to regulate vascular endothelial growth factor (VEGF) expression, and thereby tumor angiogenesis. The ability of food components to influence the inducible form of cyclooxygenase, COX-2 may also contribute to their impact on tumor growth and angiogenesis. This review focuses on recent developments related to the angiogenic role of the iNOS-VEGF axis and how dietary components may target this axis. Overall, studies suggest that the anti-angiogenic potential of physiologically concentrations of relevant food components could be used as a practical approach for cancer prevention and intervention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Food*
  • Humans
  • Neoplasms / enzymology
  • Neoplasms / metabolism*
  • Neoplasms / physiopathology
  • Neoplasms / prevention & control*
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / physiopathology
  • Neovascularization, Pathologic / prevention & control*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type II / metabolism*
  • Phytotherapy / methods*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / metabolism*


  • Vascular Endothelial Growth Factor A
  • Nitric Oxide Synthase Type II