Acacetin Inhibits VEGF Expression, Tumor Angiogenesis and Growth Through AKT/HIF-1α Pathway

Biochem Biophys Res Commun. 2011 Sep 23;413(2):299-305. doi: 10.1016/j.bbrc.2011.08.091. Epub 2011 Aug 27.

Abstract

Acacetin (5,7-dihydroxy-4'-methoxyflavone) is a flavone compound, some of which have anti-cancerous effects. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and tumor growth. In this study, we found that acacetin decreased the steady level of VEGF mRNA level and inhibited VEGF transcriptional activation. To further determine the potential mechanism of acacetin in inhibiting VEGF expression, we showed that acacetin inhibited HIF-1α expression and AKT activation. Over-expression of HIF-1α or AKT restored acacetin-decreasing VEGF transcriptional activation, indicating that AKT and HIF-1 are the essential downstream targets of acacetin for inhibiting VEGF expression in the cells. Moreover, acacetin significantly inhibited ovarian cancer cell-induced angiogenesis and tumor growth in vivo through inhibiting HIF-1α and VEGF expression. Acacetin did not change HIF-1α mRNA level, but inhibited HIF-1α protein level through increasing its degradation and decreasing its stability. These results indicate that acacetin may be a useful natural compound for ovarian cancer prevention and treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Female
  • Flavones / therapeutic use*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice
  • Neovascularization, Pathologic / drug therapy*
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / prevention & control
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / biosynthesis
  • Transcriptional Activation / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Angiogenesis Inhibitors
  • Flavones
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Proto-Oncogene Proteins c-akt
  • acacetin