Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from laminaria saccharina brown seaweed

• Autores: Croci, D.O.; Cumashi, A.; Ushakova, N.A.; Preobrazhenskaya, M.E.; Piccoli, A.; Totani, L.; Ustyuzhanina, N.E.; Bilan, M.I.; Usov, A.I.; Grachev, A.A.; Morozevich, G.E.; Berman, A.E.; Sanderson, C.J.; Kelly, M.; Gregorio, P.; Rossi, C.; Tinari, N.; Iacobelli, S.; Rabinovich, G.A.; Nifantiev, N.E.
• Año de publicación: 2011
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: PLoS ONE 2011;6(2)
• Materia: bovine serum albumin; carbohydrate derivative; fibroblast growth factor; hemoglobin; o sulfated mannoglucuronofucan derivative; plasminogen activator inhibitor 1; polysaccharide sulfate; sulfated fucan derivative; unclassified drug; angiogenesis inhibitor; anticoagulant agent; antiinflammatory agent; biological product; fucoidin; fucose; polysaccharide; angiogenesis; animal experiment; animal model; antiangiogenic activity; anticoagulation; antiinflammatory activity; antineoplastic activity; article; biological activity; breast cancer; cancer growth; cancer inhibition; cell level; cell surface; controlled study; drug determination; drug efficacy; drug isolation; drug structure; endothelium cell; fibroblast; human; human cell; in vitro study; in vivo study; Laminaria; Laminaria saccharina; leukocyte migration inhibition; melanoma; melanoma cell; mouse; nonhuman; partial thromboplastin time; peritonitis; rat; thrombocyte adhesion; tumor vascularization; animal; brown alga; C57BL mouse; cell culture; chemistry; drug effect; evaluation; female; inflammation; Laminaria; metabolism; pathology; physiology; seaweed; Wistar rat; Bovinae; Mus; Rattus; Saccharina latissima; Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Anticoagulants; Biological Products; Cells, Cultured; Endothelial Cells; Female; Fucose; Humans; Inflammation; Laminaria; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Phaeophyta; Polysaccharides; Rats; Rats, Wistar; Seaweed
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

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 fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (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 basic fibroblast growth factor (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. © 2011 Croci et al.
Fil:Croci, D.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.