Browse > Article
http://dx.doi.org/10.5483/BMBRep.2016.49.9.069

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

Choi, Sik-Won (Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA))
Lee, Kwang-Sik (Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA))
Lee, Jin Hwan (Division of Research Development and Education, National Institute of Chemical Safety, Ministry of Environment)
Kang, Hyeon Jung (Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA))
Lee, Mi Ja (Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA))
Kim, Hyun Young (Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA))
Park, Kie-In (Division of Biological Sciences, College of Natural Science, Chonbuk National University)
Kim, Sun-Lim (Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA))
Shin, Hye Kyoung (Department of surgery, Gangnam Severance Hospital, Yonsei University College of Medicine)
Seo, Woo Duck (Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA))
Publication Information
BMB Reports / v.49, no.9, 2016 , pp. 508-513 More about this Journal
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.
Keywords
Akt-HIF-1α signaling; Angiogenesis; Diacetyl atractylodiol; HIF-1α; Hypoxia;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Graeber TG, Osmanian C, Jacks T et al (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379, 88-91   DOI
2 Hill RP, Marie-Egyptienne DT and Hedley DW (2009) Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol 19, 106-111   DOI
3 Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR and Brown JM (2010) Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest 120, 694-705   DOI
4 Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S and Comoglio PM (2003) Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3, 347-361   DOI
5 Mole DR, Blancher C, Copley RR et al (2009) Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem 284, 16767-16775   DOI
6 Xia X, Lemieux ME, Li W et al (2009) Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A 106, 4260-4265   DOI
7 Belozerov VE and Van Meir EG (2005) Hypoxia inducible factor-1: a novel target for cancer therapy. Anticancer Drugs 16, 901-909   DOI
8 Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285, 1182-1186   DOI
9 Giaccia A, Siim BG and Johnson RS (2003) HIF-1 as a target for drug development. Nat Rev Drug Discov 2, 803-811   DOI
10 Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3, 721-732   DOI
11 Moehler TM, Ho AD, Goldschmidt H and Barlogie B (2003) Angiogenesis in hematologic malignancies. Crit Rev Oncol Hematol 45, 227-244   DOI
12 Onken J, Torka R, Korsing S et al (2016) Inhibiting receptor tyrosine kinase AXL with small molecule inhibitor BMS-777607 reduces glioblastoma growth, migration, and invasion in vitro and in vivo. Oncotarget 7, 9876-9889   DOI
13 Paauwe M, Heijkants RC, Oudt CH et al (2016) Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer. Oncogene 25, 1-11
14 Placencio VR, Ichimura A, Miyata T and DeClerck YA (2015) Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti- Angiogenic Activity. PLoS One 10, e0133786   DOI
15 Carmeliet P and Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298-307   DOI
16 del Puerto-Nevado L, Rojo F, Zazo S et al (2014) Active angiogenesis in metastatic renal cell carcinoma predicts clinical benefit to sunitinib-based therapy. Br J Cancer 110, 2700-2707   DOI
17 Jang MH, Shin MC, Kim YJ, Kim CJ, Kim Y and Kim EH (2004) Atractylodes japonica suppresses lipopolysaccharide-stimulated expressions of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages. Biol Pharm Bull 27, 324-327   DOI
18 Choi KH, Jeong SI, Lee JH et al (2011) Acetylene compound isolated from Atractylodes japonica stimulates the contractility of rat distal colon via inhibiting the nitrergic-purinergic relaxation. J Ethnopharmacol 134, 104-110   DOI
19 Jeong SI, Kim SY, Kim SJ et al (2010) Antibacterial activity of phytochemicals isolated from Atractylodes japonica against methicillin-resistant Staphylococcus aureus. Molecules 15, 7395-7402   DOI
20 Kiso Y, Tohkin M and Hikino H (1983) Antihepatotoxic principles of Atractylodes rhizomes. J Nat Prod 46, 651-654   DOI
21 Satoh K, Nagai F, Ushiyama K and Kano I (1996) Specific inhibition of Na+,K(+)-ATPase activity by atractylon, a major component of byaku-jutsu, by interaction with enzyme in the E2 state. Biochem Pharmacol 51, 339-343   DOI
22 Burk D and Schade AL (1956) On respiratory impairment in cancer cells. Science 124, 270-272
23 Conway EM, Collen D and Carmeliet P (2001) Molecular mechanisms of blood vessel growth. Cardiovasc Res 49, 507-521   DOI
24 Schuler M and Green DR (2001) Mechanisms of p53-dependent apoptosis. Biochem Soc Trans 29, 684-688   DOI
25 Semenza GL (1999) Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 15, 551-578   DOI
26 Hatake K, Doi T, Uetake H, Takahashi Y, Ishihara Y and Shirao K (2016) Bevacizumab safety in Japanese patients with colorectal cancer. Jpn J Clin Oncol 46, 234-240   DOI
27 Laughner E, Taghavi P, Chiles K, Mahon PC and Semenza GL (2001) HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol 21, 3995-4004   DOI
28 Levy AP, Levy NS, Wegner S and Goldberg MA (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270, 13333-13340   DOI
29 Thomas GV, Tran C, Mellinghoff IK et al (2006) Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med 12, 122-127   DOI
30 Westra J, Brouwer E, Bos R et al (2007) Regulation of cytokine-induced HIF-1alpha expression in rheumatoid synovial fibroblasts. Ann N Y Acad Sci 1108, 340-348   DOI
31 Jiang BH, Zheng JZ, Aoki M and Vogt PK (2000) Phospha-tidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci U S A 97, 1749-1753   DOI
32 Yang Y, Sun M, Wang L and Jiao B (2013) HIFs, angiogenesis, and cancer. J Cell Biochem 114, 967-974   DOI
33 Lin M, Hu Y, Chen Y et al (2012) Impacts of hypoxiainducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization. Invest Ophthalmol Vis Sci 53, 6197-6206   DOI
34 Zhao W, Wang YS, Hui YN et al (2008) Inhibition of proliferation, migration and tube formation of choroidal microvascular endothelial cells by targeting HIF-1alpha with short hairpin RNA-expressing plasmid DNA in human RPE cells in a coculture system. Graefes Arch Clin Exp Ophthalmol 246, 1413-1422   DOI
35 Ruas JL and Poellinger L (2005) Hypoxia-dependent activation of HIF into a transcriptional regulator. Semin Cell Dev Biol 16, 514-522   DOI
36 Aebersold DM, Burri P, Beer KT et al (2001) Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res 61, 2911-2916
37 Rozen S and Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132, 365-386
38 Unruh A, Ressel A, Mohamed HG et al (2003) The hypoxia-inducible factor-1 alpha is a negative factor for tumor therapy. Oncogene 22, 3213-3220   DOI
39 Choi SW, Moon SH, Yang HJ et al (2013) Antiresorptive activity of bacillus-fermented antler extracts: inhibition of osteoclast differentiation. Evidence-based complementary and alternative medicine : eCAM 2013, 748687
40 Choi SW, Son YJ, Yun JM and Kim SH (2012) Fisetin Inhibits Osteoclast Differentiation via Downregulation of p38 and c-Fos-NFATc1 Signaling Pathways. Evidence-based complementary and alternative medicine : eCAM 2012, 810563
41 Livak KJ and Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.) 25, 402-408   DOI
42 Yeon JT, Ryu BJ, Choi SW et al (2014) Natural polyamines inhibit the migration of preosteoclasts by attenuating Ca2+-PYK2-Src-NFATc1 signaling pathways. Amino Acids 46, 2605-2614   DOI
43 Kim KH, Jung HJ and Kwon HJ (2013) A new antiangiogenic small molecule, G0811, inhibits angiogenesis via targeting hypoxia inducible factor (HIF)-1alpha signal transduction. Biochem Biophys Res Commun 441, 399-404   DOI
44 Chang Q, Jurisica I, Do T and Hedley DW (2011) Hypoxia predicts aggressive growth and spontaneous metastasis formation from orthotopically grown primary xenografts of human pancreatic cancer. Cancer Res 71, 3110-3120   DOI
45 Semenza GL (2000) Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol 35, 71-103   DOI
46 Cairns RA, Harris IS and Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11, 85-95   DOI