title: Suppression of Akt-HIF-1α signaling axis by diacetyl atractylodiol inhibits hypoxia-induced angiogenesis.
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].
authors.affiliation: Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365; College of Crop Science and Biotechnology, Dankook University, Cheonan 31116, Korea.
authors.forename: Kwang-Sik
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Division of Research Development and Education, National Institute of Chemical Safety, Ministry of Environment, Daejeon 34111, Korea.
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.
authors.forename: Hyeon Jung
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.
authors.forename: Mi Ja
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju 54896, Korea.
authors.forename: Kie-In
authors.initials: KI
authors.lastname: Park
authors.affiliation: Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.
authors.forename: Sun-Lim
authors.initials: SL
authors.lastname: Kim
authors.affiliation: Department of surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea.
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea.
authors.forename: Woo Duck
authors.initials: WD
authors.lastname: Seo
mesh_terms: D031174:Atractylodes / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000502:physiology; D003035:Cobalt / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D053281:Enediynes / Q000494:pharmacology*; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D053281:Enediynes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; C007290:diacetylatractylodiol; D051057:Proto-Oncogene Proteins c-akt; C018021:cobaltous chloride