Advertisement

Cytotechnology

, Volume 47, Issue 1–3, pp 117–126 | Cite as

Enzyme-digested Fucoidan Extracts Derived from Seaweed Mozuku of Cladosiphon novae-caledoniae kylin Inhibit Invasion and Angiogenesis of Tumor Cells

  • Jun Ye
  • Yuping Li
  • Kiichiro Teruya
  • Yoshinori Katakura
  • Akira Ichikawa
  • Hiroshi Eto
  • Mutsutaka Hosoi
  • Masako Hosoi
  • Shinji Nishimoto
  • Sanetaka Shirahata
Article

Abstract

Fucoidan is a uniquely-structured sulfated polysaccharide found in the cell walls of several types of brown seaweed that has recently, especially as enzyme-digested fucoidan extract, attracted a lot attention due to its anti-tumor potential. In this study, we evaluated the effects of enzyme-digested fucoidan extracts prepared from seaweed Mozuku of Cladosiphon novae-caledoniae kylin on in vitro invasion and angiogenesis abilities of human tumor cells. First, we evaluated the effect of the fucoidan extracts on oxidative stress of tumor cells, and demonstrated that intracellular H2O2 level and released H2O2 from tumor cells were both greatly repressed upon the treatment with the fucoidan extracts, suggesting that fucoidan extracts ameliorate oxidative stress of tumor cells. Next, we tested for the effects of fucoidan extracts on invasion ability of human fibrosarcoma HT1080 cells, showing that fucoidan extracts significantly inhibit their invasion, possibly via suppressing matrix metalloproteinases (MMPs) MMP-2/9 activities. Further, we investigated the effects of the fucoidan extracts on angiogenesis of human uterine carcinoma HeLa cells, and found that fucoidan extracts suppressed expression and secretion of an angiogenesis factor vascular endothelial growth factor (VEGF), resulting in suppressed vascular tubules formation of tumor cells. The results taken together clarified that enzyme-digested fucoidan extracts from Cladosiphon novae-caledoniae kylin possess inhibitory effects on invasion and angiogenesis of tumor cells. These effects might, at least partially, be elicited by the antioxidative potential of enzyme digested fucoidan extracts.

Keywords

Angiogenesis Antitumor activity Fucoidan Invasion Matrix metalloproteinase VEGF 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agarwal, A., Munoz-Najar, U., Klueh, U., Shih, S.C., Claffey, K.P. 2004N-acetyl-cysteine promotes angiostatin production and vascular collapse in an orthotopic model of breast cancerAm. J. Pathol.16416831696PubMedGoogle Scholar
  2. Albini, A., Morini, M., D’Agostini, F., Ferrari, N., Campelli, F., Arena, G., Noonan, D.M., Pesce, C., Flora, S. 2001Inhibition of angiogenesis-driven Kaposi's sarcoma tumor growth in nude mice by oral N-acetylcysteineCancer Res.6181718178PubMedGoogle Scholar
  3. Balsari, A., Maier, J.A., Colnaghi, M.I., Menard, S. 1999Correlation between tumor vascularity, vascular endothelial growth factor production by tumor cells, serum vascular endothelial growth factor levels, and serum angiogenic activity in patients with breast carcinomaLab. Invest.79897902PubMedGoogle Scholar
  4. Belkhiri, A., Richards, C., Whaley, M., McQueen, S.A., Orr, F.W. 1997Increased expression of activated matrix metalloproteinase-2 by human endothelial cells after sublethal H2O2 exposureLab. Invest.77533539PubMedGoogle Scholar
  5. Berkman, R.A., Merrill, M.J., Reinhold, W.C., Monacci, W.T., Saxena, A., Clark, W.C., Robertson, J.T., Ali, I.U., Oldfield, E.H. 1993Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasmsJ. Clin. Invest.91153159PubMedCrossRefGoogle Scholar
  6. Brauchle, M., Funk, J.O., Kind, P., Werner, S. 1996Ultraviolet B and H2O2 are potent inducers of vascular endothelial growth factor expression in cultured keratinocytesJ Biol Chem2712179321797PubMedCrossRefGoogle Scholar
  7. Chabut, D., Fischer, A.-M., Colliec-Jouault, S., Laurendeau, I., Matou, S., Le Bonniec, B., Helley, D. 2003Low molecular weight fucoidan and heparin enhance the basic fibroblast growth factor-induced tube formation of endothelial cells through heparin sulfate-dependent a6 overexpressionMol. Pharmcol.64696702CrossRefGoogle Scholar
  8. Chabut, D., Fischer, A.M., Helley, D., Colliec, S. 2004Low molecular weight fucoidan promotes FGF-2-induced vascular tube formation by human endothelial cells, with decreased PAI-1 release and ICAM-1 downregulationThrombosis Res.1139395CrossRefGoogle Scholar
  9. Cho, M., Hunt, T.K., Hussain, M.Z. 2001Hydrogen peroxide stimulates macrophage vascular endothelial growth factor releaseAm. J. Physiol. Heart Circ. Physiol.280H23572363PubMedGoogle Scholar
  10. Chua, C.C., Hamdy, R.C., Chua, B.H. 1998Upregulation of vascular endothelial growth factor by H2O2 in rat heart endothelial cellsFree Radic. Biol. Med.25891897CrossRefPubMedGoogle Scholar
  11. Ferrara, N. 1993Vascular endothelial growth factorTrends Cardiovasc. Med.3244250CrossRefGoogle Scholar
  12. Grote, K., Flach, I., Luchtefeld, M., Akin, E., Holland, S.M., Drexler, H., Schieffer, B. 2003Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen speciesCirc. Res.92e8086CrossRefPubMedGoogle Scholar
  13. Guidi, A.J., Abu-Jawdeh, G., Berse, B., Jackman, R.W., Tognazzi, K., Dvorak, H.F., Brown, L.F. 1995Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasiaJ. Natl. Cancer Inst.8712371245PubMedCrossRefGoogle Scholar
  14. Gurjar, M.V., Deleon, J., Sharma, R.V., Bhalla, R.C. 2001Role of reactive oxygen species in IL-1 beta-stimulated sustained ERK activation and MMP-9 inductionAm. J. Physiol. Heart Circ. Physiol.281H25682574PubMedGoogle Scholar
  15. Haroun-Bouhedja, F., Lindenmeyer, F., Lu, H., Soria, C., Jozefonvicz, J., Boisson-Vidal, C. 2002In vitro effects of fucans on DA-MB231 tumor cell adhesion and invasionAnticancer Res.2222852292PubMedGoogle Scholar
  16. Hoyoku, H. 1995Cancer chemoprevention by natural carotenoids and their related compoundsJ. Cell. Biochem. Suppl.22231235Google Scholar
  17. Itoh, H., Noda, H., Amano, H., Zhuang, C., Mizuno, T., Ito, H. 1993Antitumor activity and immunological properties of marine algal polysaccharides, especially Fucoidan, prepared from Sargassum thunbergii of PheophyceaeAnticancer Res.1320452052PubMedGoogle Scholar
  18. Johnsen, M., Lund, L.R., Romer, J., Almholt, K., Dano, K. 1998Cancer invasion and tissue remodeling: common themes in proteolytic matrix degradationCurr. Opin. Cell Biol.106676671CrossRefPubMedGoogle Scholar
  19. Johnson, L.L., Dyer, R., Hupe, D.J. 1998Matrix metalloproteinasesCurr. Opin. Chem. Biol.2466471PubMedCrossRefGoogle Scholar
  20. Kolev, K., Skopal, J., Simon, L., Csonka, E., Machovich, R., Nagy, Z. 2003Matrix metalloproteinase-9 expression in post-hypoxic human brain capillary endothelial cells: H2O2 as a trigger and NF-kappaB as a signal transducerThromb. Haemost.90528537PubMedGoogle Scholar
  21. Koyanagi, S., Tanigawa, N., Nakagawa, H., Soeda, S., Shimeno, H. 2003Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activitiesBiochem. Phamacol.65173179CrossRefGoogle Scholar
  22. Liabakk, N.B., Talbot, I., Smith, R.A., Wilkinson, K., Balkwill, F. 1996Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancerCancer Res.56190196PubMedGoogle Scholar
  23. Malafa, M.P., Fokum, F.D., Smith, L., Louis, A. 2002Inhibition of angiogenesis and promotion of melanoma dormancy by vitamin E succinateAnn. Surg. Oncol.910231032CrossRefPubMedGoogle Scholar
  24. Maruyama, H., Tamauchi, H., Hashimoto, M., Nakano, T. 2003Antitumor activity and immune response of Mekabu Fucoidan extracted from Sporophyll of Undaria pinnatifida In Vivo17245249PubMedGoogle Scholar
  25. Masuda, M., Suzui, M., Lim, J.T., Deguchi, A., Soh, J.W., Weinstein, I.B. 2002Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transductionJ. Exp. Ther. Oncol.2350359CrossRefPubMedGoogle Scholar
  26. Mattern, J., Koomagi, R., Volm, M. 1996Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumor cell proliferation in human epidermoid lung carcinomaBr. J. Cancer73931934PubMedGoogle Scholar
  27. Noda, H., Amano, H., Arashima, K., Nisizawa, K. 1990Antitumor activity of marine algaeHydrobiologica204–205577584CrossRefGoogle Scholar
  28. Okuzumi, J., Nishino, H., Murakoshi, M., Iwashima, A., Tanaka, Y., Yamane, T., Fujita, Y., Takahashi, T. 1990Inhibitory effects of fucoxanthin, a natural carotenoidon N-myc expression and cell cycle progression in human malignant tumor cellsCancer Lett.557581CrossRefPubMedGoogle Scholar
  29. Okuzumi, J., Takahashi, T., Yamane, T., Kitao, Y., Inagake, M., Ohya, K., Nishino, H., Tanaka, Y. 1993Inhibitory effects of fucoxanthin, a natural carotenoidon N-ethyl-N′-nitro-N-nitrosoguanidine-induced mouse duodenal carcinogenesisCancer Lett.68159168CrossRefPubMedGoogle Scholar
  30. Qian, Y., Luo, J., Leonard, S.S., Harris, G.K., Millecchia, L., Flynn, D.C., Shi, X. 2003Hydrogen peroxide formation and actin filament reorganization by Cdc42 are essential for ethanol-induced in vitro angiogenesisJ. Biol. Chem.2781618916197PubMedCrossRefGoogle Scholar
  31. Quanbin, Z., Pengzhan, Y., Zhien, L., Hong, Z., Zuhong, X., Pengcheng, L. 2003Antioxidant activities of sulfated polysaccharide fractions from Porphyra haitanesis J. Appl. Phycol.15305310CrossRefGoogle Scholar
  32. Ruch, W., Cooper, P.H., Baggiolini, M. 1983Assay of H2O2 production by macrophages and neutrophils with homovanillic acid and horse-radish peroxidaseJ. Immunol. Methods63347357CrossRefPubMedGoogle Scholar
  33. Ruperez, P., Ahrazem, O., Leal, J.A. 2002Potential antioxidant capacity of sulfated polysaccharides from the edible marine brown seaweed Fucus vesiculosus J. Agric. Food Chem.50840845CrossRefPubMedGoogle Scholar
  34. Soeda, S., Ishida, S., Shimeno, H., Nagamatsu, A. 1994Inhibitory effect of oversulfated fucoidan on invasion through reconstituted basement membrane by murine Lewis lung carcinomaJpn. J. Cancer Res.8511441150PubMedGoogle Scholar
  35. Suzuki, K., Hayashi, N., Miyamoto, Y., Yamamoto, M., Ohkawa, K., Ito, Y., Sasaki, Y., Yamaguchi, Y., Nakase, H., Noda, K., Enomoto, N., Arai, K., Yamada, Y., Yoshihara, H., Tujimura, T., Kawano, K., Yoshikawa, K., Kamada, T. 1996Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinomaCancer Res.5630043009PubMedGoogle Scholar
  36. Szatrowski, T.P., Nathan, C.F. 1991Production of large amounts of hydrogen peroxide by human tumor cellsCancer Res.51794798PubMedGoogle Scholar
  37. Tang, F.Y., Meydani, M. 2001Green tea catechins and vitamin E inhibit angiogenesis of human microvascular endothelial cells through suppression of IL-8 productionNutr. Cancer41119125PubMedCrossRefGoogle Scholar
  38. Usui, T., Asari, K., Mizuno, T. 1980Isolation of highly purified “Fucoidan” from Eisenia bicycliosits anticoagulant and antitumor activitiesAgric. Biol. Chem.4419651966Google Scholar
  39. Westermarck, J., Kahari, V.M. 1999Regulation of matrix metalloproteinase expression in tumor invasionFaseb. J.13781792PubMedGoogle Scholar
  40. Wizigmann-Voos, S., Breier, G., Risau, W., Plate, K.H. 1995Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomasCancer Res.5513581364PubMedGoogle Scholar
  41. Xue, C.-H., Fang, Y., Lin, H., Chen, L., Li, Z.-J., Deng, D., Lu, C.-X. 2001Chemical characters and antioxidative properties of sulfated polysaccharides from Laminaria japonica J. Appl. Phycol.136770CrossRefGoogle Scholar
  42. Xue, C., Yu, G., Hirata, T., Terao, J., Lin, H. 1998Antioxidative activities of several marine polysaccharides evaluated in a phosphatidylcholine-liposomal suspension and organic solventsBiosci. Biotechnol. Biochem.62206209PubMedCrossRefGoogle Scholar
  43. Xue, Z., Chang-Hu, X., Zhao-Jie, L., Yue-Piao, C., Hong-Ying, L, Hong-Tao, Q. 2004Antioxidant and hepatoprotective activities of low molecular weight sulfated polysaccharide from Laminaria japonica J. Appl. Phycol.16111115CrossRefGoogle Scholar
  44. Yamamoto, I., Takahashi, M., Suzuki, T., Seino, H., Mori, H. 1984Antitumor effect of seaweeds. IV. Enhancement of antitumor activity by sulfation of a crude Fucoidan from Sargassum kjellmanianum Jpn. J. Exp. Med.54143151PubMedGoogle Scholar
  45. Zhang, Q., Li, N., Zhou, G., Lu, X., Xu, Z., Li, Z. 2003In vivo antioxidant activity of polysaccharide fraction from Porphyra haitanesis (Rhodephyta) in aging micePharmacol. Res.48151155PubMedCrossRefGoogle Scholar
  46. Zhu, J.W., Yu, B.M., Ji, Y.B., Zheng, M.H., Li, D.H. 2002Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancerWorld J. Gastroenterol.8153157PubMedGoogle Scholar
  47. Zhuang, C., Itoh, H., Mizuno, T., Ito, H. 1995Antitumor active Fucoidan from the brown seaweedUmitoranoo (Aargassum thunbergii)Biosci. Biotech. Biochem.59563567CrossRefGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Jun Ye
    • 1
  • Yuping Li
    • 1
  • Kiichiro Teruya
    • 1
  • Yoshinori Katakura
    • 1
  • Akira Ichikawa
    • 2
  • Hiroshi Eto
    • 3
  • Mutsutaka Hosoi
    • 4
  • Masako Hosoi
    • 5
  • Shinji Nishimoto
    • 6
  • Sanetaka Shirahata
    • 1
  1. 1.Department of Genetic Resources Technology, Faculty of AgricultureKyushu UniversityFukuokaJapan
  2. 2.Department of Applied BiologyKyoto Institute of TechnologySakyo-ku, KyotoJapan
  3. 3.Daiichi Sangyo Co. Ltd.OsakaJapan
  4. 4.Hosoi Dermatological ClinicFukuokaJapan
  5. 5.Department of Clinical Medicine, Faculty of Medical SciencesKyushu UniversityJapan
  6. 6.Nishimoto Daini ClinicWakayamaJapan

Personalised recommendations