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Antiproliferative Activity of Fucan Nanogel
Laboratory of Biotechnology of Natural Polymers (BIOPOL), Departament of Biochemistry, Federal University of Rio Grande do Norte (UFRN), Natal-RN 59078-970, Brazil
Graduate Program in Health Sciences, Federal University of Rio Grande do Norte (UFRN), Natal-RN 59078-970, Brazil
IBB—Institute for Biotechnology and Bioengineering, Centre for Biological Engineering, Minho University, Braga 4704-553, Portugal
* Author to whom correspondence should be addressed.
Received: 18 August 2012; in revised form: 8 September 2012 / Accepted: 11 September 2012 / Published: 17 September 2012
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.
Keywords: nanogels; cancer cells; sulfated polysaccharides; Spatoglossum schröederi
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Dantas-Santos, N.; Almeida-Lima, J.; Vidal, A.A.J.; Lopes Gomes, D.; Medeiros Oliveira, R.; Santos Pedrosa, S.; Pereira, P.; Gama, F.M.; Oliveira Rocha, H.A. Antiproliferative Activity of Fucan Nanogel. Mar. Drugs 2012, 10, 2002-2022.
Dantas-Santos N, Almeida-Lima J, Vidal AAJ, Lopes Gomes D, Medeiros Oliveira R, Santos Pedrosa S, Pereira P, Gama FM, Oliveira Rocha HA. Antiproliferative Activity of Fucan Nanogel. Marine Drugs. 2012; 10(9):2002-2022.
Dantas-Santos, Nednaldo; Almeida-Lima, Jailma; Vidal, Arthur Anthunes Jacome; Lopes Gomes, Dayanne; Medeiros Oliveira, Ruth; Santos Pedrosa, Silvia; Pereira, Paula; Gama, Francisco Miguel; Oliveira Rocha, Hugo Alexandre. 2012. "Antiproliferative Activity of Fucan Nanogel." Mar. Drugs 10, no. 9: 2002-2022.