FUCANS, BUT NOT FUCOMANNOGLUCURONANS, DETERMINE THE BIOLOGICAL ACTIVITIES OF SULFATED POLYSACCHARIDES FROM LAMINARIA SACCHARINA BROWN SEAWEED

CROCI DIEGO; CUMASHI ALBANA; USHAKOVA NATALIA; PREOBRAZHENSKAYA, MARINA; PICCOLI, ANTONIO; TOTANI LICIA; USTYUZHANINA NADEZHDA; BILAN MARIA; USOV ANATOLLI; GRACHEV ALEXEY; MOROZEVICH GALINA; BERMAN ALBERT; SANDERSON CRAIG; KELLY MAEVE; DI GREGORI PATRIZIA; TINARI NICOLA; IACOBELLI STEFANO; RABINOVICH GABRIEL*; NIFANTIEV NIKOLAY* (GR & NN CONTRIBUYERON IGUAL A ESTE TRABAJO)

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: Washington; Año: 2011 vol. 6 p. 17283 - 17292

1932-6203

Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited FBS-induced in vitro tubulogenesis. This effect correlated with a reduction in PAI-1 levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of bFGF-induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed.