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

• Published in: BMB reports Vol. 49; no. 9; pp. 508 - 513
• Main Authors: Choi, Sik-Won, Lee, Kwang-Sik, Lee, Jin Hwan, Kang, Hyeon Jung, Lee, Mi Ja, Kim, Hyun Young, Park, Kie-In, Kim, Sun-Lim, Shin, Hye Kyoung, Seo, Woo Duck
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 30.09.2016; 생화학분자생물학회
• Subjects: 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; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2016.49.9.069

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].