Suppression of Akt-HIF-1α signaling axis by diacetyl atractylodiol inhibits hypoxia-induced angiogenesis

BMB Rep. 2016 Sep;49(9):508-13. doi: 10.5483/bmbrep.2016.49.9.069.

Abstract

Hypoxia-inducible factor (HIF)-1α is a key regulator associated with tumorigenesis, angiogenesis, and metastasis. HIF-1α regulation under hypoxia has been highlighted as a promising therapeutic target in angiogenesis-related diseases. Here, we demonstrate that diacetyl atractylodiol (DAA) from Atractylodes japonica (A. japonica) is a potent HIF-1α inhibitor that inhibits the Akt signaling pathway. DAA dose-dependently inhibited hypoxia-induced HIF-1α and downregulated Akt signaling without affecting the stability of HIF-1α protein. Furthermore, DAA prevented hypoxia-mediated angiogenesis based on in vitro tube formation and in vivo chorioallantoic membrane (CAM) assays. Therefore, DAA might be useful for treatment of hypoxia-related tumorigenesis, including angiogenesis. [BMB Reports 2016; 49(9): 508-513].

MeSH terms

  • Atractylodes / chemistry
  • Atractylodes / metabolism
  • Blotting, Western
  • Chorioallantoic Membrane / drug effects
  • Chorioallantoic Membrane / physiology
  • Cobalt / toxicity
  • Down-Regulation / drug effects
  • Enediynes / pharmacology*
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Neovascularization, Physiologic / drug effects*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Enediynes
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • Cobalt
  • diacetylatractylodiol
  • Proto-Oncogene Proteins c-akt
  • cobaltous chloride