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

• Autores: Croci Russo, Diego Omar; Cumashi, Albana; Ushakova, Natalia A.; Preobrazhenskaya, Marina E.; Piccoli, Antonio; Totani, Licia; Ustyuzhanina, Nadezhda E.; Bilan, María I.; Usov, Anatolii I.; Grachev, Alexey A.; Morozevich, Galina E.; Berman, Albert E.; Sanderson, Craig J.; Kelly, Maeve; Di Gregorio, Patrizia; Rossi, Cosmo; Tinari, Nicola; Iacobelli, Stefano; Rabinovich, Gabriel Adrián; Nifantiev, Nicolay E.
• Año de publicación: 2011
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Fucose; Angiogenesis; Endothelial Cells; Saccharina
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Cumashi, Albana. Universita degli Studi "G. D Annunzio"; Italia
Fil: Ushakova, Natalia A.. Russian Academy of Medical Science; Rusia
Fil: Preobrazhenskaya, Marina E.. Russian Academy of Medical Science; Italia
Fil: Piccoli, Antonio. Consorzio Mario Negri Sud; Italia
Fil: Totani, Licia. Consorzio Mario Negri Sud; Italia
Fil: Ustyuzhanina, Nadezhda E.. Russian Academy of Medical Science; Rusia
Fil: Bilan, María I.. Russian Academy of Medical Science; Rusia
Fil: Usov, Anatolii I.. Russian Academy of Medical Science; Rusia
Fil: Grachev, Alexey A.. Russian Academy of Medical Science; Rusia
Fil: Morozevich, Galina E.. Russian Academy of Medical Science; Rusia
Fil: Berman, Albert E.. Russian Academy of Medical Science; Rusia
Fil: Sanderson, Craig J.. Scottish Association for Marine Sciences; Reino Unido
Fil: Kelly, Maeve. Scottish Association for Marine Sciences; Reino Unido
Fil: Di Gregorio, Patrizia. Universita degli Studi "G. D Annunzio"; Italia
Fil: Rossi, Cosmo. Universita degli Studi "G. D Annunzio"; Italia
Fil: Tinari, Nicola. Universita degli Studi "G. D Annunzio"; Italia
Fil: Iacobelli, Stefano. Universita degli Studi "G. D Annunzio"; Italia
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Nifantiev, Nicolay E.. Russian Academy of Medical Science; Rusia