Fisheries and Aquatic Sciences

The Korean Society of Fisheries and Aquatic Science (한국수산과학회)
권호 표지
DOI QR코드

DOI QR Code

Dieckol Suppresses CoCl2-induced Angiogenesis in Endothelial Cells

  • Jung, Seung Hyun (Department of Chemistry, Pukyong National University) ;
  • Jang, In Seung (Department of Chemistry, Pukyong National University) ;
  • Jeon, You-Jin (Department of Marine Life Science, Jeju National University) ;
  • Kim, Young-Mog (Department of Food Science & Technology, Pukyong National University) ;
  • Park, Sun Joo (Department of Chemistry, Pukyong National University)
  • Received : 2014.07.11
  • Accepted : 2014.07.15
  • Published : 2014.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Dieckol is a polyphenol compound isolated from brown algae that has anti-oxidant, anti-inflammatory, and anti-tumor activity. We examined the anti-angiogenic effects of dieckol in endothelial cells under hypoxic conditions. Treatment with $CoCl_2$, a hypoxic mimetic agent, increased proliferation, adhesion, migration, and tube formation in HUVECs, as well as vessel sprouting in rat aortic rings, which correlated well with increased expression of hypoxia-inducible factor 1-alpha ($HIF1{\alpha}$) and ${\beta}1$-integrin. Dieckol suppressed $CoCl_2$-induced adhesion, migration, and tube formation in HUVECs and vessel sprouting in rat aortic rings. Dieckol treatment decreased $CoCl_2$-induced overexpression of $HIF1{\alpha}$ and its downstream signaling molecules, including ${\beta}1$-integrin/Fak, Akt/eNOS, and p38 MAPK. These results suggest that dieckol is a novel angiogenesis inhibitor and a potential treatment for angiogenesis-dependent diseases in humans, such as malignant tumors.

Keywords

References

  1. Bader BL, Rayburn H, Crowley D and Hynes RO. 1998. Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell 95, 507-519. https://doi.org/10.1016/S0092-8674(00)81618-9
  2. Berry DA, Balcar VJ, Barden JA, Keogh A and dos Remedios CG. 2000. Determination of P2X1alpha-sarcoglycan (adhalin) expression levels in failing human dilated cardiomyopathic left ventricles. Electrophoresis 21, 3857-3862. https://doi.org/10.1002/1522-2683(200011)21:17<3857::AID-ELPS3857>3.0.CO;2-R
  3. Bix G, Fu J, Gonzalez EM, Macro L, Barker A, Campbell S, Zutter MM, Santoro SA, Kim JK, Hook M, Reed CC and Iozzo RV. 2004. Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin. J Cell Biol 166, 97-109. https://doi.org/10.1083/jcb.200401150
  4. Bloch W, Forsberg E, Lentini S, Brakebusch C, Martin K, Krell HW, Weidle UH, Addicks K and Fassler R. 1997. Beta 1 integrin is essential for teratoma growth and angiogenesis. J Cell Biol 139, 265-278. https://doi.org/10.1083/jcb.139.1.265
  5. Brooks PC, Clark RA and Cheresh DA. 1994. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264, 569-571. https://doi.org/10.1126/science.7512751
  6. Bussolino F, Mantovani A and Persico G. 1997. Molecular mechanisms of blood vessel formation. Trends Biochem Sci 22, 251-256. https://doi.org/10.1016/S0968-0004(97)01074-8
  7. Coultas L, Chawengsaksophak K and Rossant J. 2005. Endothelial cells and VEGF in vascular development. Nature 438, 937-945. https://doi.org/10.1038/nature04479
  8. Distler JH, Jungel A, Pileckyte M, Zwerina J, Michel BA, Gay RE, Kowal-Bielecka O, Matucci-Cerinic M, Schett G, Marti HH, Gay S and Distler O. 2007. Hypoxia-induced increase in the production of extracellular matrix proteins in systemic sclerosis. Arthritis Rheum 56, 4203-4215. https://doi.org/10.1002/art.23074
  9. Ferrara N. 2005. VEGF as a therapeutic target in cancer. Oncol 69, 11-16. https://doi.org/10.1159/000088479
  10. Fidler IJ and Ellis LM. 1994. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 79, 185-188. https://doi.org/10.1016/0092-8674(94)90187-2
  11. Francis SE, Goh KL, Hodivala-Dilke K, Bader BL, Stark M, Davidson D and Hynes RO. 2002. Central roles of alpha5beta1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies. Arterioscler Thromb Vasc Biol 22, 927-933. https://doi.org/10.1161/01.ATV.0000016045.93313.F2
  12. Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA and Cheresh DA. 1995. Definition of two angiogenic pathways by distinct alpha v integrins. Science 270, 1500-1502. https://doi.org/10.1126/science.270.5241.1500
  13. Hanahan D. Signaling vascular morphogenesis and maintenance. 1997. Science 277, 48-50. https://doi.org/10.1126/science.277.5322.48
  14. Heo SJ, Ko SC, Cha SH, Kang DH, Park HS, Choi YU, Kim D, Jung WK and Jeon YJ. 2009. Effect of phlorotannins isolated from Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation. Toxicol in Vitro 23, 1123-1130. https://doi.org/10.1016/j.tiv.2009.05.013
  15. Irigoyen M, Anso E, Salvo E, Dotor de las Herrerias J, Martinez-Irujo JJ and Rouzaut A. 2008. TGFbeta-induced protein mediates lymphatic endothelial cell adhesion to the extracellular matrix under low oxygen conditions. Cell Mol Life Sci 65, 2244-2255. https://doi.org/10.1007/s00018-008-8071-9
  16. Jiang BH, Jiang G, Zheng JZ, Lu Z, Hunter T and Vogt PK. 2001. Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth Differ 12, 363-369.
  17. Kim YM, Kim KE, Koh GY, Ho YS and Lee KJ. 2006. Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis. Cancer Res 66, 6167-6174. https://doi.org/10.1158/0008-5472.CAN-05-3640
  18. Krock BL, Skuli N and Simon MC. Hypoxia-induced angiogenesis: good and evil. 2011. Genes Cancer 2, 1117-1133. https://doi.org/10.1177/1947601911423654
  19. Lee SH, Han JS, Heo SJ, Hwang JY and Jeon YJ. 2010. Protective effects of dieckol isolated from Ecklonia cava against high glucoseinduced oxidative stress in human umbilical vein endothelial cells. Toxicol in Vitro 24, 375-381. https://doi.org/10.1016/j.tiv.2009.11.002
  20. Li L, Liu F, Welser-Alves JV, McCullough LD and Milner R. 2012. Upregulation of fibronectin and the alpha5beta1 and alphavbeta3 integrins on blood vessels within the cerebral ischemic penumbra. Exp Neurol 233, 283-291. https://doi.org/10.1016/j.expneurol.2011.10.017
  21. Liu LZ, Hu XW, Xia C, He J, Zhou Q, Shi X, Fang J and Jiang BH. 2006. Reactive oxygen species regulate epidermal growth factorinduced vascular endothelial growth factor and hypoxia-inducible factor-1alpha expression through activation of AKT and P70S6K1 in human ovarian cancer cells. Free Radic Biol Med 41, 1521-1533. https://doi.org/10.1016/j.freeradbiomed.2006.08.003
  22. Lo YY and Cruz TF. 1995. Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes. J Biol Chem 270, 11727-11730. https://doi.org/10.1074/jbc.270.20.11727
  23. Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, Hankinson O, Pugh CW and Ratcliffe PJ. 1997. Hypoxiainducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 94, 8104-8109. https://doi.org/10.1073/pnas.94.15.8104
  24. Medici D and Olsen BR. 2012. Rapamycin inhibits proliferation of hemangioma endothelial cells by reducing HIF-1-dependent expression of VEGF. PLoS One 7, e42913. https://doi.org/10.1371/journal.pone.0042913
  25. Mettouchi A and Meneguzzi G. 2006. Distinct roles of beta1 integrins during angiogenesis. Eur J Cell Biol 85, 243-247. https://doi.org/10.1016/j.ejcb.2005.09.010
  26. Millar TM, Phan V and Tibbles LA. 2007. ROS generation in endothelial hypoxia and reoxygenation stimulates MAP kinase signaling and kinase-dependent neutrophil recruitment. Free Radic Biol Med 42, 1165-1177. https://doi.org/10.1016/j.freeradbiomed.2007.01.015
  27. Min JK, Han KY, Kim EC, Kim YM, Lee SW, Kim OH, Kim KW, Gho YS and Kwon YG. 2004. Capsaicin inhibits in vitro and in vivo angiogenesis. Cancer Res 64, 644-651. https://doi.org/10.1158/0008-5472.CAN-03-3250
  28. Newcomb EW, Ali MA, Schnee T, Lan L, Lukyanov Y, Fowkes M, Miller DC and Zagzag D. 2005. Flavopiridol downregulates hypoxia-mediated hypoxia-inducible factor-1alpha expression in human glioma cells by a proteasome-independent pathway: implications for in vivo therapy. Neuro Oncol 7, 225-235. https://doi.org/10.1215/S1152851704000997
  29. Nicosia RF and Ottinetti A. 1990. Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: a comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot. In Vitro Cell Dev Biol 26, 119-128. https://doi.org/10.1007/BF02624102
  30. Niewiarowska J, Brezillon S, Sacewicz-Hofman I, Bednarek R, Maquart FX, Malinowski M, Wiktorska M, Wegrowski Y and Cierniewski CS. 2011. Lumican inhibits angiogenesis by interfering with alpha-2beta1 receptor activity and downregulating MMP-14 expression. Thromb Res 128, 452-457. https://doi.org/10.1016/j.thromres.2011.06.011
  31. Papapetropoulos A, Garcia-Cardena G, Madri JA and Sessa WC. 1997. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100, 3131-3139. https://doi.org/10.1172/JCI119868
  32. Park SJ and Jeon YJ. 2012. Dieckol from Ecklonia cava suppresses the migration and invasion of HT1080 cells by inhibiting the focal adhesion kinase pathway downstream of Rac1-ROS signaling. Mol Cells 33, 141-149. https://doi.org/10.1007/s10059-012-2192-6
  33. Pirone DM, Liu WF, Ruiz SA, Gao L, Raghavan S, Lemmon CA, Romer LH and Chen CS. 2006. An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling. J Cell Biol 174, 277-288. https://doi.org/10.1083/jcb.200510062
  34. Rafii S and Lyden D. 2003. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 9, 702-712. https://doi.org/10.1038/nm0603-702
  35. Risau W. 1997. Mechanisms of angiogenesis. Nature 386, 671-674. https://doi.org/10.1038/386671a0
  36. Sudhakar A, Sugimoto H, Yang C, Lively J, Zeisberg M and Kalluri R. 2003. Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins. Proc Nat'l Acad Sci USA 100, 4766-4771. https://doi.org/10.1073/pnas.0730882100
  37. Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR and Jiang BH. 2007. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res 67, 10823-10830. https://doi.org/10.1158/0008-5472.CAN-07-0783
  38. Zachary I and Gliki G. 2001. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res 49, 568-581. https://doi.org/10.1016/S0008-6363(00)00268-6
  39. Zagzag D, Nomura M, Friedlander DR, Blanco CY, Gagner JP, Nomura N and Newcomb EW. 2003. Geldanamycin inhibits migration of glioma cells in vitro: a potential role for hypoxia-inducible factor (HIF-1alpha) in glioma cell invasion. J Cell Physiol 196, 394-402. https://doi.org/10.1002/jcp.10306
  40. Zhou Q, Liu LZ, Fu B, Hu X, Shi X, Fang J and Jiang BH. 2007. Reactive oxygen species regulate insulin-induced VEGF and HIF-1alpha expression through the activation of p70S6K1 in human prostate cancer cells. Carcinogenesis 28, 28-37. https://doi.org/10.1093/carcin/bgl085