A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds.
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.
Cumashi
Albana
A
Department of Oncology and Neurosciences, University G. D'Annunzio Medical School & Foundation, 66013 Chieti, Italy, and Division of Immunogenetics, Hospital de Clínicas José de San Martín, Buenos Aires, Argentina.
Ushakova
Natalia A
NA
Preobrazhenskaya
Marina E
ME
D'Incecco
Armida
A
Piccoli
Antonio
A
Totani
Licia
L
Tinari
Nicola
N
Morozevich
Galina E
GE
Berman
Albert E
AE
Bilan
Maria I
MI
Usov
Anatolii I
AI
Ustyuzhanina
Nadezhda E
NE
Grachev
Alexey A
AA
Sanderson
Craig J
CJ
Kelly
Maeve
M
Rabinovich
Gabriel A
GA
Iacobelli
Stefano
S
Nifantiev
Nikolay E
NE
D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000459:Phaeophyceae / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D012624:Seaweed / Q000737:chemistry; D013927:Thrombosis / Q000188:drug therapy / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017395:Plasminogen Activator Inhibitor 1; D011134:Polysaccharides; C007789:fucoidan