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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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(A-B) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of bFGF-induced HUVEC tubulogenesis.(A) Representative photographs of HUVEC cultured on Matrigel in the presence of bFGF along with 100 µg/ml of the indicated polysaccharide preparations. (B) Quantitative analysis of tube-like structures. All data were expressed as the percentage of tubes/cm2 vs control (bFGF). (C,D) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of Balb/c 3T3 adhesion to bFGF. (C) Effects of L.s.-P and L.s.-1.25 on fibroblast cell adhesion to bFGF. Representative images of fibroblast cell adhesion to purified bFGF are shown. The images are representative of three independent experiments. Quantification was performed by counting adhered cells of at least three different fields. Results are expressed as percentage of the treated sample with respect to control (D). ***P<0.001.
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pone-0017283-g004: (A-B) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of bFGF-induced HUVEC tubulogenesis.(A) Representative photographs of HUVEC cultured on Matrigel in the presence of bFGF along with 100 µg/ml of the indicated polysaccharide preparations. (B) Quantitative analysis of tube-like structures. All data were expressed as the percentage of tubes/cm2 vs control (bFGF). (C,D) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of Balb/c 3T3 adhesion to bFGF. (C) Effects of L.s.-P and L.s.-1.25 on fibroblast cell adhesion to bFGF. Representative images of fibroblast cell adhesion to purified bFGF are shown. The images are representative of three independent experiments. Quantification was performed by counting adhered cells of at least three different fields. Results are expressed as percentage of the treated sample with respect to control (D). ***P<0.001.

Mentions: bFGF is an essential mediator capable of regulating angiogenesis [18]. We examined whether the parent fucoidan from L. saccharina or its fractions could selectively modulate bFGF-mediated events. We initially investigated the effect of such polysaccharides by targeting bFGF-induced HUVEC tubulogenesis For such assay, each polysaccharide and bFGF were added before plating HUVEC onto Matrigel. As shown in Figure 4A–B, addition of 100 µg/ml parent fucoidan from L. saccharina (L.s.-P) or the L.s.-1.25 fraction blocked (99% inhibition, P<0.001) bFGF-induced HUVEC tube formation, while L.s.-1.0 had no effect.


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)

(A-B) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of bFGF-induced HUVEC tubulogenesis.(A) Representative photographs of HUVEC cultured on Matrigel in the presence of bFGF along with 100 µg/ml of the indicated polysaccharide preparations. (B) Quantitative analysis of tube-like structures. All data were expressed as the percentage of tubes/cm2 vs control (bFGF). (C,D) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of Balb/c 3T3 adhesion to bFGF. (C) Effects of L.s.-P and L.s.-1.25 on fibroblast cell adhesion to bFGF. Representative images of fibroblast cell adhesion to purified bFGF are shown. The images are representative of three independent experiments. Quantification was performed by counting adhered cells of at least three different fields. Results are expressed as percentage of the treated sample with respect to control (D). ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017283-g004: (A-B) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of bFGF-induced HUVEC tubulogenesis.(A) Representative photographs of HUVEC cultured on Matrigel in the presence of bFGF along with 100 µg/ml of the indicated polysaccharide preparations. (B) Quantitative analysis of tube-like structures. All data were expressed as the percentage of tubes/cm2 vs control (bFGF). (C,D) Specific effect of L.s.-P and its fractions L.s.-1.0 and L.s.-1.25 on the inhibition of Balb/c 3T3 adhesion to bFGF. (C) Effects of L.s.-P and L.s.-1.25 on fibroblast cell adhesion to bFGF. Representative images of fibroblast cell adhesion to purified bFGF are shown. The images are representative of three independent experiments. Quantification was performed by counting adhered cells of at least three different fields. Results are expressed as percentage of the treated sample with respect to control (D). ***P<0.001.
Mentions: bFGF is an essential mediator capable of regulating angiogenesis [18]. We examined whether the parent fucoidan from L. saccharina or its fractions could selectively modulate bFGF-mediated events. We initially investigated the effect of such polysaccharides by targeting bFGF-induced HUVEC tubulogenesis For such assay, each polysaccharide and bFGF were added before plating HUVEC onto Matrigel. As shown in Figure 4A–B, addition of 100 µg/ml parent fucoidan from L. saccharina (L.s.-P) or the L.s.-1.25 fraction blocked (99% inhibition, P<0.001) bFGF-induced HUVEC tube formation, while L.s.-1.0 had no effect.

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