FUCANS, SULFATED POLYSACCHARIDES EXTRACTED FROM BROWN SEAWEEDS, INHIBIT VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION .2. DEGRADATION AND MOLECULAR-WEIGHT EFFECT

Fucan, a sulfated polysaccharide extracted from brown seaweeds, inhibi ts smooth muscle cell (SMC) proliferation with a higher antiproliferat ive activity than heparin (Logeart et al., fur. J. Cell Biol. 74, 1997 , this issue). In order to investigate the structure-activity relation ship of fucan on SMC growth, we have prepared by size exclusion chroma tography bean frictions of various molecular masses ranging from 5.5 t o 556 kDa. Our experiments showed that the antiproliferative activity is dependent on the molecular weight of the polysaccharide. The molecu lar weight threshold indicated that about 30 saccharidic units on fuca n were necessary to give the antiproliferative activity an SMCs. A kin etics study of DNA synthesis using tritiated thymidine uptake,vas also performed with different molecular weight bean fractions. Although al l tested fractions acted as soon as the cells enter the first cell cyc le, the duration and potency of action varied. Moreover, displacement experiments of iodinated bean revealed that the low molecular fucan fr action interacted weakly with the binding sites. Finally gel permeatio n chromatography of internalized radiolabeled heparin and beans was pe rformed with SMCs. A rapid degradation of internalized heparin was obs erved, whereas only low molecular weight bean fractions were partially degraded by SMCs. Together, these results indicate the significance o f molecular weight on the antiproliferative activity of beans 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 antiprol iferative effect on SMCs.