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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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Micrograph of 786 cells treated with SNFuc. These cells were incubated with 0.5 mg/mL SNFuc for 24 h and labeled with DAPI to show nuclear morphology. (A) Control 786 cells, without SNFuc; (B) 786 cells treated with SNFuc, showing nuclear morphological changes such as pyknosis (arrows). Bar, 10 µm.
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marinedrugs-10-02002-f007: Micrograph of 786 cells treated with SNFuc. These cells were incubated with 0.5 mg/mL SNFuc for 24 h and labeled with DAPI to show nuclear morphology. (A) Control 786 cells, without SNFuc; (B) 786 cells treated with SNFuc, showing nuclear morphological changes such as pyknosis (arrows). Bar, 10 µm.

Mentions: The 786 cells were exposed to SNFuc (0.5 mg/mL) for 24 h. Contrast microscopy showed that most cells became circular (Data not shown). Nuclear morphological changes were observed by DAPI staining. In the control group, 786 cells were rounded and homogeneously stained (Figure 7A). After 24 h of treatment with SNFuc, blebbing nuclei, pycnotic bodies, morphological alterations and granular apoptotic bodies appeared (Figure 7B). Marked apoptotic morphologic alterations, including nuclear condensation, suggest nanoparticles induce apoptosis in 786 cells.


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)

Micrograph of 786 cells treated with SNFuc. These cells were incubated with 0.5 mg/mL SNFuc for 24 h and labeled with DAPI to show nuclear morphology. (A) Control 786 cells, without SNFuc; (B) 786 cells treated with SNFuc, showing nuclear morphological changes such as pyknosis (arrows). Bar, 10 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

marinedrugs-10-02002-f007: Micrograph of 786 cells treated with SNFuc. These cells were incubated with 0.5 mg/mL SNFuc for 24 h and labeled with DAPI to show nuclear morphology. (A) Control 786 cells, without SNFuc; (B) 786 cells treated with SNFuc, showing nuclear morphological changes such as pyknosis (arrows). Bar, 10 µm.
Mentions: The 786 cells were exposed to SNFuc (0.5 mg/mL) for 24 h. Contrast microscopy showed that most cells became circular (Data not shown). Nuclear morphological changes were observed by DAPI staining. In the control group, 786 cells were rounded and homogeneously stained (Figure 7A). After 24 h of treatment with SNFuc, blebbing nuclei, pycnotic bodies, morphological alterations and granular apoptotic bodies appeared (Figure 7B). Marked apoptotic morphologic alterations, including nuclear condensation, suggest nanoparticles induce apoptosis in 786 cells.

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