Journal of Applied Phycology

, Volume 23, Issue 1, pp 59–65 | Cite as

Enhanced immunostimulatory and antitumor activity of different derivatives of κ-carrageenan oligosaccharides from Kappaphycus striatum

  • Huamao Yuan
  • Jinming SongEmail author
  • Xuegang Li
  • Ning Li
  • Song Liu


Chemical modification of carbohydrates can lead to differences in their biological activities. We previously showed that κ-carrageenan oligosaccharides from Kappaphycus striatum have antitumor and immunomodulation effects on S180-bearing mice. In this study, we tested the hypothesis that different chemical modifications of carrageenan oligosaccharides enhance their activities. The mice inoculated with S180 cell suspension were treated p.o. with carrageenan oligosaccharides and their sulfated, acetylated, and phosphorylated derivatives (50, 100, and 200 μg g−1) for 14 days. Transplantable tumor inhibition rate and macrophage phagocytosis, quantitative hemolysis of sheep red blood cells, lymphocyte proliferation, the activity of natural killer cells, production of interleukin-2, and tumor necrosis factor-α were also analyzed. As expected, treatment with different κ-carrageenan oligosaccharides derivatives resulted in an increase in tumor inhibition rate and macrophage phagocytosis and cellular immunity, especially on spleen lymphocyte proliferation. The sulfated derivative at the dose 200 μg g−1 per day showed the highest antitumor activity with the 54.12% tumor weight inhibition and elicited an increase in nature killer cells activity up to 76.1% on S180-bearing mice, which were both significantly higher than the unmodified oligosaccharides. It suggested that chemical modification (especially sulfation) of carrageenan oligosaccharides can enhance their antitumor effect and boost their antitumor immunity.


Carrageenan Oligosaccharides Derivatives Antitumor Immunomodulation Chemical modification 



This work was financially supported by the Innovative Key Project of the Chinese Academy of Sciences (KZCX2-YW-209), the National Project for public welfare marine affairs (200705010), the Science and Technology Development Program of Shandong Province (2008BS06005) and the Talent program of Chinese Academy of Science (Dongbei Zhi Chun).


  1. Bland EJ, Keshavarz T, Bucke C (2004) The influence of small oligosaccharides on the immune system. Carbohydr Res 339:1673–1678CrossRefPubMedGoogle Scholar
  2. Bobek V, Boubelik M, Fišerová A, Ľuptovvová M, Vannucci L, Kacprzak G, Kolodzej J, Majewski AM, Hoffman RM (2005) Anticoagulant drugs increase natural killer cell activity in lung cancer. Lung Cancer 47:215–223CrossRefPubMedGoogle Scholar
  3. Chen HM, Yan XJ, Lin J, Wang F, Xu WF (2007) Depolymerized products of λ-carrageenan as a potent angiogenesis inhibitor. J Agric Food Chem 55:6910–6917CrossRefPubMedGoogle Scholar
  4. Ehrke MJ (2003) Immunomodulation in cancer therapeutics. Int Immunopharmacol 3:1105–1119CrossRefPubMedGoogle Scholar
  5. Franz G, Pauper D, Alban S (2000) Bioactive carbohydrate polymers. Proceedings of the Phytochemical Society of Europe, vol 44. Kluwer Academic Publishers, Dordrecht, Boston pp 47–58Google Scholar
  6. Hoffman R (1993) Carrageenans inhibit growth-factor binding. Biochem J 289:331–334PubMedGoogle Scholar
  7. Koyanagi S, Tanigawa N, Nakagawa H, Soeda S, Shimeno H (2003) Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Biochem Pharmacol 65:173–179CrossRefPubMedGoogle Scholar
  8. Li XY (2000) Immunomodulating components from chinese medicines. Pharm Biol 38(Supp):33–40CrossRefGoogle Scholar
  9. Paper DH, Vogl H, Franz G (1995) Defined carrageenan derivatives as angiogenesis inhibitors. Macromol Symp 99:219–225Google Scholar
  10. Parish CR, Freeman C, Brown KJ, Francis DJ, Cowden WB (1999) Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity. Can Res 59:3433–3441Google Scholar
  11. Rabinovich GA, Gabrilovich D, Sotomayor EM (2007) Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296CrossRefPubMedGoogle Scholar
  12. Saksena R, Deepak D, Khare A, Sahai R, Tripathi LM, Srivastava VML (1999) A novel pentasaccharide from immunostimulant oligosaccharide fraction of buffalo milk. Biochim Biophys Acta 1428:433–445PubMedGoogle Scholar
  13. Salem ML, Matsuzaki G, Madkour GA, Nomoto K (1999) Beta-estradiol-induced decrease in IL-12 and TNF-α expression suppresses macrophage functions in the course of Listeria monocytogenes infection in mice. Int J Immunopharmacol 21:481–497CrossRefPubMedGoogle Scholar
  14. Simpson MA, Gozzo JJ (1978) Spectrophotometric determination of lymphocyte mediated sheep red blood cell hemolysis in vitro. J Immunol Meth 21:159–165CrossRefGoogle Scholar
  15. Soeda S, Kozako T, Iwata K, Shimeno H (2000) Oversulfated fucoidan inhibits the basic fibroblast growth factor-induced tube formation by human umbilical vein endothelial cells: its possible mechanism of action. Biochim Biophys Acta 1497:127–134CrossRefPubMedGoogle Scholar
  16. Weymouth-Wilson AC (1997) The role of carbohydrates in biologically active natural products. Nat Prod Rep 14:99–110CrossRefPubMedGoogle Scholar
  17. Yashizawa Y, Ametani A, Tsunehiro J, Numura K, Itoh M, Fukui F (1995) Macrophage stimulation activity of the polysaccharide fraction from a marine alga (Porphyra yezoensis): structure-function relationship and improved solubility. Biosci Biotech Biochem 59:1933–1937CrossRefGoogle Scholar
  18. Yuan HM, Song JM (2005) Preparation, structural characterization and in vitro antitumor activity of kappa-carrageenan oligosaccharide fraction from Kappaphycus striatum. J Appl Phycol 17:7–13CrossRefGoogle Scholar
  19. Yuan HM, Zhang WW, Li XG, Lü XX, Li N, Gao XL, Song JM (2005) Preparation and in vitro antioxidant activity of κ-carrageenan oligosaccharides and their oversulfated, acetylated, and phosphorylated derivatives. Carbohydr Res 340:685–692CrossRefPubMedGoogle Scholar
  20. Yuan HM, Song JM, Li XG, Li N, Dai JC (2006a) Immunomodulation and antitumor activity of κ-carrageenan oligosaccharides. Canc Lett 243:228–234CrossRefGoogle Scholar
  21. Yuan HM, Song JM, Zhang WW, Li XG, Li N, Gao XL (2006b) Antioxidant activity and cytoprotective effect of κ-carrageenan oligosaccharides and their different derivatives. Bioorg Med Chem Lett 16:1329–1334CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Huamao Yuan
    • 1
  • Jinming Song
    • 1
    Email author
  • Xuegang Li
    • 1
  • Ning Li
    • 1
  • Song Liu
    • 1
  1. 1.Institute of OceanologyChinese Academy of SciencesQingdaoPeople’s Republic of China

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