Biological Properties of Ulvan, a New Source of Green Seaweed Sulfated Polysaccharides, on Cultured Normal and Cancerous Colonic Epithelial Cells

Ulvans (from Ulva lactuca) constitute a dietary fiber structurally similar to the mammalian glycosaminoglycans but with unexplored biological or cytotoxic activities. From native low-viscosity preparations containing 33.5 molar % and 18.4 molar % of sulfate residues and uronic acid residues, respectively, we derived desulfated, reduced and desulfated-reduced polysaccharides with respectively 5.2, 2.9, and 4.5-4.9 molar % of sulfate residues and uronic acid residues. The effects of these preparations were examined on the adhesion, proliferation and differentiation of normal or tumoral colonic epithelial cells cultured in conventional (0.3-0.8 x 10(6) cells/ml) or rotating bioreactor (3-8 x 10(6) cells/ml) culture conditions. In conventional culture conditions, ulvan modified the adhesion phase and the proliferation of normal colonic cells and undifferentiated HT-29 cells according to their molecular weights and to the relative molar proportion of sulfate residues. From the native polysaccharides, we have screened sulfated ulvans (MW < 5,000) which inhibited the Caco-2 cell proliferation/differentiation program by inducing a low cell reactivity to Ulex europeaus-1 lectins in defined (p < 0.001) or serum-supplemented media (p < 0.01) but were inactive on normal colonocytes. In conclusion, this dietary fiber could be a source of oligosaccharides with a bioactivity, a cytotoxicity or a cytostaticity targeted to normal or cancerous epithelial cells.