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Antiproliferative activity of fucan nanogel.

Dantas-Santos N, Almeida-Lima J, Vidal AA, Gomes DL, Oliveira RM, Santos Pedrosa S, Pereira P, Gama FM, Oliveira Rocha HA - Mar Drugs (2012)

Bottom Line: The resulting modified material (SNFuc) formed nanosized particles.On the other hand, nanogel improved Chinese hamster ovary (CHO) and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same concentration range.The antiproliferative effect against tumor cells was also confirmed using the BrdU test.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biotechnology of Natural Polymers (BIOPOL), Departament of Biochemistry, Federal University of Rio Grande do Norte (UFRN), Natal-RN 59078-970, Brazil. nednaldod@hotmail.com

ABSTRACT
Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated L-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc) formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean diameter of 123 nm and zeta potential of -38.3 ± 0.74 mV, as measured by dynamic light scattering. Nanoparticles conserved their size for up to 70 days. SNFuc cytotoxicity was determined using the MTT assay after culturing different cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5) proliferation was inhibited by 2.0%-43.7% at nanogel concentrations of 0.05-0.5 mg/mL and rabbit aorta endothelial cells (RAEC) non-tumor cell line proliferation displayed inhibition of 8.0%-22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO) and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same concentration range. The antiproliferative effect against tumor cells was also confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle.

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Structure of fucan A from Spatoglossum schroederi proposed by Leite and colleagues [16].
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marinedrugs-10-02002-f001: Structure of fucan A from Spatoglossum schroederi proposed by Leite and colleagues [16].

Mentions: The brown seaweed Spatoglossum schröederi synthesizes three heterofucans, namely fucan A, fucan B and fucan C. Our group proposes 21 kDa fucan A structure as consisting of a core of β(1–3) glucuronic acid-containing 4.5 kDa oligosaccharide, with branches at C-4 of α(1–3)-linked fucose chains. Fucose is substituted at C-4 and C-2 (minor) with sulfate groups. In addition, some fucose residues are substituted at C-2 with chains of β(1–4) xylose, which, in turn, is also partially sulfated (Figure 1) [16]. This fucan displayed no mutagenicity or genotoxicity [17]. In addition, fucan A shows no toxicity in vivo [18]. Thus, in the present study we synthesized and characterized hydrophobically modified fucan A nanogel (SNFuc), assessing their effect on several tumor and normal cell lines.


Antiproliferative activity of fucan nanogel.

Dantas-Santos N, Almeida-Lima J, Vidal AA, Gomes DL, Oliveira RM, Santos Pedrosa S, Pereira P, Gama FM, Oliveira Rocha HA - Mar Drugs (2012)

Structure of fucan A from Spatoglossum schroederi proposed by Leite and colleagues [16].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475269&req=5

marinedrugs-10-02002-f001: Structure of fucan A from Spatoglossum schroederi proposed by Leite and colleagues [16].
Mentions: The brown seaweed Spatoglossum schröederi synthesizes three heterofucans, namely fucan A, fucan B and fucan C. Our group proposes 21 kDa fucan A structure as consisting of a core of β(1–3) glucuronic acid-containing 4.5 kDa oligosaccharide, with branches at C-4 of α(1–3)-linked fucose chains. Fucose is substituted at C-4 and C-2 (minor) with sulfate groups. In addition, some fucose residues are substituted at C-2 with chains of β(1–4) xylose, which, in turn, is also partially sulfated (Figure 1) [16]. This fucan displayed no mutagenicity or genotoxicity [17]. In addition, fucan A shows no toxicity in vivo [18]. Thus, in the present study we synthesized and characterized hydrophobically modified fucan A nanogel (SNFuc), assessing their effect on several tumor and normal cell lines.

Bottom Line: The resulting modified material (SNFuc) formed nanosized particles.On the other hand, nanogel improved Chinese hamster ovary (CHO) and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same concentration range.The antiproliferative effect against tumor cells was also confirmed using the BrdU test.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biotechnology of Natural Polymers (BIOPOL), Departament of Biochemistry, Federal University of Rio Grande do Norte (UFRN), Natal-RN 59078-970, Brazil. nednaldod@hotmail.com

ABSTRACT
Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated L-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc) formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean diameter of 123 nm and zeta potential of -38.3 ± 0.74 mV, as measured by dynamic light scattering. Nanoparticles conserved their size for up to 70 days. SNFuc cytotoxicity was determined using the MTT assay after culturing different cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5) proliferation was inhibited by 2.0%-43.7% at nanogel concentrations of 0.05-0.5 mg/mL and rabbit aorta endothelial cells (RAEC) non-tumor cell line proliferation displayed inhibition of 8.0%-22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO) and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same concentration range. The antiproliferative effect against tumor cells was also confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle.

Show MeSH
Related in: MedlinePlus