Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities

Koyanagi Satoru, Noboru Tanigawa, Hiroo Nakagawa, Shinji Soeda, Hiroshi Shimeno

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has anticoagulant and antithrombotic activities. Unlike heparin, it shows an inhibitory action on the progression and metastasis of malignant tumors, although the precise mechanisms have not been elucidated. We have demonstrated previously that fucoidan can inhibit tube formation following migration of human umbilical vein endothelial cells (HUVEC) and that its chemical oversulfation enhances the inhibitory potency. In this study, we tested the hypothesis that fucoidan may suppress tumor growth by inhibiting tumor-induced angiogenesis. Both natural and oversulfated fucoidans (NF and OSF) significantly suppressed the mitogenic and chemotactic actions of vascular endothelial growth factor 165 (VEGF165) on HUVEC by preventing the binding of VEGF165 to its cell surface receptor. The suppressive effect of OSF was more potent than that of NF, suggesting an important role for the numbers of sulfate groups in the fucoidan molecule. Consistent with its inhibitory actions on VEGF165, OSF clearly suppressed the neovascularization induced by Sarcoma 180 cells that had been implanted in mice. The inhibitory action of fucoidan was also observed in the growth of Lewis lung carcinoma and B16 melanoma in mice. These results indicate that the antitumor action of fucoidan is due, at least in part, to its anti-angiogenic potency and that increasing the number of sulfate groups in the fucoidan molecule contributes to the effectiveness of its anti-angiogenic and antitumor activities.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalBiochemical Pharmacology
Volume65
Issue number2
DOIs
Publication statusPublished - Jan 15 2003
Externally publishedYes

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Tumors
Endothelial cells
Human Umbilical Vein Endothelial Cells
Sulfates
Sarcoma 180
Seaweed
Lewis Lung Carcinoma
Neoplasms
Experimental Melanomas
Molecules
fucoidan
Cell Surface Receptors
Growth
Anticoagulants
Polysaccharides
Heparin
Neoplasm Metastasis
human VEGFA protein

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. / Satoru, Koyanagi; Tanigawa, Noboru; Nakagawa, Hiroo; Soeda, Shinji; Shimeno, Hiroshi.

In: Biochemical Pharmacology, Vol. 65, No. 2, 15.01.2003, p. 173-179.

Research output: Contribution to journalArticle

Satoru, Koyanagi ; Tanigawa, Noboru ; Nakagawa, Hiroo ; Soeda, Shinji ; Shimeno, Hiroshi. / Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. In: Biochemical Pharmacology. 2003 ; Vol. 65, No. 2. pp. 173-179.
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