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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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1H NMR spectra of native fucan (A) and SNFuc in D2O at 25 °C (B) and Correlation Spectroscoy analysis (COSY spectrum) of SNFuc (C).
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marinedrugs-10-02002-f003: 1H NMR spectra of native fucan (A) and SNFuc in D2O at 25 °C (B) and Correlation Spectroscoy analysis (COSY spectrum) of SNFuc (C).

Mentions: The native fucan A 1H NMR spectrum is shown in Figure 3A. The two main α-anomeric protons, which correspond to α-L-fucose units, were observed at 5.18 and 5.08 ppm. In contrast with the simplicity of both α-fucose residues, β systems show a certain degree of multiplicity, likely due to diversity in the positions of interglycosidic linkages of sugar residues. β-Anomeric protons appeared as two unresolved multiplets centered at 4.4 and 4.9 ppm, together with signals of protons from sulfation sites, whereas the remaining fucan A protons appear in the range of 3.5–4.5 ppm [16]. Signals around 1.2–1.4 ppm were assigned to CH3 protons of fucose residues.


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)

1H NMR spectra of native fucan (A) and SNFuc in D2O at 25 °C (B) and Correlation Spectroscoy analysis (COSY spectrum) of SNFuc (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

marinedrugs-10-02002-f003: 1H NMR spectra of native fucan (A) and SNFuc in D2O at 25 °C (B) and Correlation Spectroscoy analysis (COSY spectrum) of SNFuc (C).
Mentions: The native fucan A 1H NMR spectrum is shown in Figure 3A. The two main α-anomeric protons, which correspond to α-L-fucose units, were observed at 5.18 and 5.08 ppm. In contrast with the simplicity of both α-fucose residues, β systems show a certain degree of multiplicity, likely due to diversity in the positions of interglycosidic linkages of sugar residues. β-Anomeric protons appeared as two unresolved multiplets centered at 4.4 and 4.9 ppm, together with signals of protons from sulfation sites, whereas the remaining fucan A protons appear in the range of 3.5–4.5 ppm [16]. Signals around 1.2–1.4 ppm were assigned to CH3 protons of fucose residues.

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