Antiproliferative activity of fucan nanogel

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.The present study was supported by CAPES, MCT, FAPERN/CNPq and CNPq, Brazil, as well as FCT, Portugal. N Dantas-Santos, J Almeida-Lima, AAJ Vidal, HAO Rocha are grateful to the CNPq and CAPES for their fellowship support. This research was submitted to the Graduate Program in Health Sciences at the Federal University of Rio Grande do Norte as part of the D.Sc. thesis of ND-S

Fucan effect on CHO cell proliferation and migration

Fucan is a term used to denominate sulfated L-fucose rich polysaccharides. Here, a heterofucan, named fucan B, was extracted from the Spatoglossum schroederi seaweed. This 21.5 kDa galactofucan inhibited CHO-Kl proliferation and migration when fibronectin was the substrate. Fucan B derivatives revealed that such effects depend on their degree of sulfation. Fucan B did not induce cell death, but promoted G1 cell cycle arrest. Western blotting and flow cytometry analysis suggest that fucan B binds to fibronectin and activates integrin, mainly integrin alpha 5 beta 1, which induces FAK/RAS/MEK/ERK activation. FAK activation inhibits CHO-K1 migration on fibronectin and ERK blocks cell cycle progression. This study indicates that fucan B could be applied in developing new antitumor drugs. (C) 2013 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)MCTFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPERNCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Rio Grande do Norte, Dept Bioquim, BR-59072970 Natal, RN, BrazilUniversidade Federal de São Paulo, Depto Bioquim, Disciplina Biol Mol, São Paulo, BrazilUniv Fed Parana, Dept Biol Celular, BR-80060000 Curitiba, PR, BrazilUniversidade Federal de São Paulo, Depto Bioquim, Disciplina Biol Mol, São Paulo, BrazilWeb of Scienc