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

Croci DO, Cumashi A, Ushakova NA, Preobrazhenskaya ME, Piccoli A, Totani L, Ustyuzhanina NE, Bilan MI, Usov AI, Grachev AA, Morozevich GE, Berman AE, Sanderson CJ, Kelly M, Di Gregorio P, Rossi C, Tinari N, Iacobelli S, Rabinovich GA, Nifantiev NE, Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO), Ita - PLoS ONE (2011)

Bottom Line: This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas y Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.

ABSTRACT
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.

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Putative structures of the main components of the fractions L.s.-1.0 (A) and L.s.-1.25 (B) obtained from the total sulfated polysaccharide preparation L.s.-P extracted from L. saccharina.
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pone-0017283-g001: Putative structures of the main components of the fractions L.s.-1.0 (A) and L.s.-1.25 (B) obtained from the total sulfated polysaccharide preparation L.s.-P extracted from L. saccharina.

Mentions: Here we investigated the biological profiles of two main components of the parent sulfated polysaccharide extracted from L. saccharina (L.s.-P). Serial fractionation by ion-exchange chromatography produced two main fractions differing in the monosaccharide composition and sulfate content [10]. The first fraction eluted from DEAE-Sephacel by 1.0 M NaCl (L.s.-1.0) consisted mainly of sulfated fucomannoglucuronan (Figure 1A) and not of fucoidan-related polysaccharides. The second fraction eluted by 1.25 M NaCl (L.s.-1.25) consisted mainly of sulfated fucans (Figure 1B), which structurally corresponds to the previously reported fucoidan from L. saccharina [11]. The presence of fucomannoglucuronan component in L.s.-P was surprising as this component was not clearly visible in the NMR spectra of L.s.-P [11]. To determine how L.s.-1.0 and L.s.-1.25 account for the biology activities of L.s.-P, we performed comparative studies of these purified fractions in terms of anti-inflammatory, anti-coagulant, anti-angiogenic, anti-tumor, and anti-adhesive functions. Results presented here provide for the first time, experimental evidence in vitro and in vivo showing that it is possible to dissect out the chemical structures responsible for the anti-inflammatory, anti-angiogenic, and anti-tumor activities of sulfated polysaccharides from L. saccharina.


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

Croci DO, Cumashi A, Ushakova NA, Preobrazhenskaya ME, Piccoli A, Totani L, Ustyuzhanina NE, Bilan MI, Usov AI, Grachev AA, Morozevich GE, Berman AE, Sanderson CJ, Kelly M, Di Gregorio P, Rossi C, Tinari N, Iacobelli S, Rabinovich GA, Nifantiev NE, Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO), Ita - PLoS ONE (2011)

Putative structures of the main components of the fractions L.s.-1.0 (A) and L.s.-1.25 (B) obtained from the total sulfated polysaccharide preparation L.s.-P extracted from L. saccharina.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046160&req=5

pone-0017283-g001: Putative structures of the main components of the fractions L.s.-1.0 (A) and L.s.-1.25 (B) obtained from the total sulfated polysaccharide preparation L.s.-P extracted from L. saccharina.
Mentions: Here we investigated the biological profiles of two main components of the parent sulfated polysaccharide extracted from L. saccharina (L.s.-P). Serial fractionation by ion-exchange chromatography produced two main fractions differing in the monosaccharide composition and sulfate content [10]. The first fraction eluted from DEAE-Sephacel by 1.0 M NaCl (L.s.-1.0) consisted mainly of sulfated fucomannoglucuronan (Figure 1A) and not of fucoidan-related polysaccharides. The second fraction eluted by 1.25 M NaCl (L.s.-1.25) consisted mainly of sulfated fucans (Figure 1B), which structurally corresponds to the previously reported fucoidan from L. saccharina [11]. The presence of fucomannoglucuronan component in L.s.-P was surprising as this component was not clearly visible in the NMR spectra of L.s.-P [11]. To determine how L.s.-1.0 and L.s.-1.25 account for the biology activities of L.s.-P, we performed comparative studies of these purified fractions in terms of anti-inflammatory, anti-coagulant, anti-angiogenic, anti-tumor, and anti-adhesive functions. Results presented here provide for the first time, experimental evidence in vitro and in vivo showing that it is possible to dissect out the chemical structures responsible for the anti-inflammatory, anti-angiogenic, and anti-tumor activities of sulfated polysaccharides from L. saccharina.

Bottom Line: This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas y Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus