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Glycobiology Advance Access originally published online on February 12, 2007
Glycobiology 2007 17(5):541-552; doi:10.1093/glycob/cwm014
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds

Albana Cumashi2, Natalia A. Ushakova3, Marina E. Preobrazhenskaya3, Armida D'Incecco2, Antonio Piccoli4, Licia Totani4, Nicola Tinari2, Galina E. Morozevich3, Albert E. Berman3, Maria I. Bilan5, Anatolii I. Usov5, Nadezhda E. Ustyuzhanina6, Alexey A. Grachev6, Craig J. Sanderson7, Maeve Kelly7, Gabriel A. Rabinovich8, Stefano Iacobelli2, Nikolay E. Nifantiev and on behalf of the Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO), Italy1,6

2 Department of Oncology and Neurosciences, University G. D'Annunzio Medical School & Foundation, 66013 Chieti, Italy
3 V.N. Orekhovich Research Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya str. 10, 119121 Moscow, Russian Federation
4 Consorzio Mario Negri Sud, Laboratory of Vascular Biology and Pharmacology, Santa Maria Imbaro, Chieti 66030, Italy
5 Laboratory of plant polysaccharides
6 Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prospect, 119991 Moscow, Russia
7 Scottish Association for Marine Sciences, Oban, Argyll, Scotland, PA37 1QA, UK
8 Division of Immunogenetics, Hospital de Clínicas "José de San Martín," Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina


1 To whom correspondence should be addressed; Tel/Fax: +7-495-1358784; e-mail: nen{at}ioc.ac.ru

Received on May 24, 2006; revised on January 14, 2007; accepted on February 2, 2007

The anti-inflammatory, antiangiogenic, anticoagulant, and antiadhesive properties of fucoidans obtained from nine species of brown algae were studied in order to examine the influence of fucoidan origin and composition on their biological activities. All fucoidans inhibited leucocyte recruitment in an inflammation model in rats, and neither the content of fucose and sulfate nor other structural features of their polysaccharide backbones significantly affected the efficacy of fucoidans in this model. In vitro evaluation of P-selectin-mediated neutrophil adhesion to platelets under flow conditions revealed that only polysaccharides from Laminaria saccharina, L. digitata, Fucus evanescens, F. serratus, F. distichus, F. spiralis, and Ascophyllum nodosum could serve as P-selectin inhibitors. All fucoidans, except that from Cladosiphon okamuranus carrying substantial levels of 2-O-{alpha}-D-glucuronopyranosyl branches in the linear (1 -> 3)-linked poly-{alpha}-fucopyranoside chain, exhibited anticoagulant activity as measured by activated partial thromboplastin time whereas only fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. evanescens displayed strong antithrombin activity in a platelet aggregation test. The last fucoidans potently inhibited human umbilical vein endothelial cell (HUVEC) tubulogenesis in vitro and this property correlated with decreased levels of plasminogen-activator inhibitor-1 in HUVEC supernatants, suggesting a possible mechanism of fucoidan-induced inhibition of tubulogenesis. Finally, fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. vesiculosus strongly blocked MDA-MB-231 breast carcinoma cell adhesion to platelets, an effect which might have critical implications in tumor metastasis. The data presented herein provide a new rationale for the development of potential drugs for thrombosis, inflammation, and tumor progression.

Key words: fucoidan / brown algae / blood coagulation / inflammation / angiogenesis


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