Fucoidan inhibits smooth muscle cell proliferation and reduces mitogen-activated protein kinase activity.
OBJECTIVE
fucoidan has previously been shown to inhibit the proliferation of arterial smooth muscle cells both in animal models and in vitro. However, the mechanisms behind the anti-proliferative effects of this polysulfated polysaccharide are not known in detail. Here, the inhibitory effect of fucoidan on rat aortic smooth muscle cell proliferation was examined and compared with the effects of heparin after stimulation with fetal calf serum, platelet-derived growth factor BB, basic fibroblast growth factor, heparin-binding epidermal growth factor, and angiotensin II.


METHODS
the cultures were analysed with respect to cell proliferation and DNA synthesis by cell counting and measurement of(3)H-thymidine incorporation. Phosphorylation of mitogen-activated protein kinase and nuclear translocation of phosphorylated mitogen-activated protein kinase were studied by immunoblotting and immunocytochemistry.


RESULTS
fucoidan was shown to be a more potent inhibitor of smooth muscle cell proliferation than heparin. Fucoidan also reduced growth factor-induced activation of mitogen-activated protein kinase and prevented nuclear translocation of phosphorylated mitogen-activated protein kinase.


CONCLUSIONS
fucoidan is a more potent anti-proliferative polysulphated polysaccharide than heparin and may mediate its effects through inhibition of the mitogen-activated protein kinase pathway in a similar manner as heparin.
Religa
P
P
Department of Surgical Sciences, Division of Vascular Surgery, SE-171 76 Stockholm, Sweden.
Kazi
M
M
Thyberg
J
J
Gaciong
Z
Z
Swedenborg
J
J
Hedin
U
U
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D011134:Polysaccharides; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D006493:Heparin; D004247:DNA; C007789:fucoidan; D020928:Mitogen-Activated Protein Kinases