Acacetin inhibits in vitro and in vivo angiogenesis and downregulates Stat signaling and VEGF expression

Cancer Prev Res (Phila). 2013 Oct;6(10):1128-39. doi: 10.1158/1940-6207.CAPR-13-0209. Epub 2013 Aug 13.


Angiogenesis is an effective target in cancer control. The antiangiogenic efficacy and associated mechanisms of acacetin, a plant flavone, are poorly known. In the present study, acacetin inhibited growth and survival (up to 92%; P < 0.001), and capillary-like tube formation on Matrigel (up to 98%; P < 0.001) by human umbilical vein endothelial cells (HUVEC) in regular condition, as well as VEGF-induced and tumor cells conditioned medium-stimulated growth conditions. It caused retraction and disintegration of preformed capillary networks (up to 91%; P < 0.001). HUVEC migration and invasion were suppressed by 68% to 100% (P < 0.001). Acacetin inhibited Stat-1 (Tyr701) and Stat-3 (Tyr705) phosphorylation, and downregulated proangiogenic factors including VEGF, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and basic fibroblast growth factor (bFGF) in HUVEC. It also suppressed nuclear localization of pStat-3 (Tyr705). Acacetin strongly inhibited capillary sprouting and networking from rat aortic rings and fertilized chicken egg chorioallantoic membrane (CAM; ∼71%; P < 0.001). Furthermore, it suppressed angiogenesis in Matrigel plugs implanted in Swiss albino mice. Acacetin also inhibited tyrosine phosphorylation of Stat-1 and -3, and expression of VEGF in cancer cells. Overall, acacetin inhibits Stat signaling and suppresses angiogenesis in vitro, ex vivo, and in vivo, and therefore, it could be a potential agent to inhibit tumor angiogenesis and growth.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Capillaries / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane / metabolism
  • Collagen / chemistry
  • Drug Combinations
  • Endothelial Cells / cytology
  • Flavones / therapeutic use*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Laminin / chemistry
  • Male
  • Mice
  • Microscopy, Fluorescence
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic*
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Proteoglycans / chemistry
  • Rats
  • Rats, Wistar
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction*
  • Tyrosine / chemistry
  • Vascular Endothelial Growth Factor A / metabolism*


  • Antineoplastic Agents
  • Drug Combinations
  • Flavones
  • Laminin
  • Proteoglycans
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • matrigel
  • Tyrosine
  • Collagen
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • acacetin