Cinnamon extract reduces VEGF expression via suppressing HIF-1α gene expression and inhibits tumor growth in mice

Mol Carcinog. 2017 Feb;56(2):436-446. doi: 10.1002/mc.22506. Epub 2016 Jun 15.


Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cinnamon (CE) was a potent inhibitor of VEGF production in human cancer cells and suggested inhibition might be mediated through the suppression of HIF-1α gene expression and protein synthesis. Furthermore, CE treatment was found to inhibit expression and phosphorylation of STAT3 and AKT, which are key factors in the regulation of HIF-1α expression, and significantly reduce angiogenesis potential of cancer cells by migration assay. Consistent with these results, we observed significant suppression of VEGF expression, blood vessel formation, and tumor growth in a human ovarian tumor model in mice treated with CE. Cinnamaldehyde, a major component in cinnamon, was identified as one active component in CE that inhibits VEGF expression. Taken together, our findings provide a novel mechanism underlying anti-angiogenic and anti-tumor actions of CE and support the potential use of CE in cancer prevention and treatment. © 2016 Wiley Periodicals, Inc.

Keywords: HIF-1α; VEGF; angiogenesis; cinnamon extract; xenograft.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Cinnamomum zeylanicum / chemistry*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice, SCID
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Ovary / blood supply
  • Ovary / drug effects*
  • Ovary / metabolism
  • Ovary / pathology
  • Plant Extracts / chemistry
  • Plant Extracts / therapeutic use
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism


  • Antineoplastic Agents, Phytogenic
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Plant Extracts
  • Vascular Endothelial Growth Factor A