Fucans, sulfated polysaccharides extracted from brown seaweeds, inhibit vascular smooth muscle cell proliferation. II. Degradation and molecular weight effect.
Fucan, a sulfated polysaccharide extracted from brown seaweeds, inhibits smooth muscle cell (SMC) proliferation with a higher antiproliferative activity than heparin (Logeart et al., Eur. J. Cell Biol. 74, 1997, this issue). In order to investigate the structure-activity relationship of fucan on SMC growth, we have prepared by size exclusion chromatography fucan fractions of various molecular masses ranging from 5.5 to 556 kDa. Our experiments showed that the antiproliferative activity is dependent on the molecular weight of the polysaccharide. The molecular weight threshold indicated that about 30 saccharidic units on fucan were necessary to give the antiproliferative activity on SMCs. A kinetics study of DNA synthesis using tritiated thymidine uptake was also performed with different molecular weight fucan fractions. Although all tested fractions acted as soon as the cells enter the first cell cycle, the duration and potency of action varied. Moreover, displacement experiments of iodinated fucan revealed that the low molecular fucan fraction interacted weakly with the binding sites. Finally, gel permeation chromatography of internalized radiolabeled heparin and fucans was performed with SMCs. A rapid degradation of internalized heparin was observed, whereas only low molecular weight fucan fractions were partially degraded by SMCs. Together, these results indicate the significance of molecular weight on the antiproliferative activity of fucans on SMCs, and might help to understand their mechanism of action. In addition, the degradation experiments with internalized heparin and fucans ruled out a direct link between polysaccharide degradation and the antiproliferative effect on SMCs.
Logeart
D
D
LRM, CNRS URA 502, INFREMER URM2, University Paris XIII, France.
Prigent-Richard
S
S
Boisson-Vidal
C
C
Chaubet
F
F
Durand
P
P
Jozefonvicz
J
J
Letourneur
D
D
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002458:Cell Fractionation; D002478:Cells, Cultured; D006131:Growth Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010936:Plant Extracts; D011134:Polysaccharides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012624:Seaweed; D013431:Sulfates
D006131:Growth Inhibitors; D010936:Plant Extracts; D011134:Polysaccharides; D013431:Sulfates; D006493:Heparin