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Fucoidan is a natural sulfated polysaccharide with a large range of biological activities including anticancer and anti-oxidation activities. Hepatocellular carcinoma is the fourth most common aggressive cancer type. The aim of this study was to investigate the bioactivity of free fucoidan versus its vectorization using nanoparticles (NPs) in human hepatoma cells, Huh-7. Iron oxide NPs were functionalized with fucoidan by a one-step surface complexation. NP cellular uptake was quantified by magnetic measurement at various extracellular iron concentrations. Cell invasion and migration were reduced with NPs while free fucoidan increases these events at low fucoidan concentration (≤0.5 μM). Concomitantly, a high decrease of reactive oxygen species production related with a decrease of the matrix metalloproteinase-9 activity and an increase of its expression was observed with NPs compared to free fucoidan. A proteomic analysis evidenced that some fucoidan regulated proteins appeared, which were related to protein synthesis, N-glycan processing, and cellular stress. To our knowledge, this is the first study which reveals such activity induced by fucoidan. These results pave the way for USPIO-fucoidan-NPs as potential theranostic nanotools for hepatocellular carcinoma treatment.

This paper describes the preparation and the biological evaluation of α-halogenated oxaphosphinanes. These halogen derivatives were synthetized from a short and stereoselective synthetic sequence starting by previously described hydroxy-precursors 1 and 2 with respectively a glucose and mannose-like configuration. The in vitro biological tests of these unnatural halogenated phosphinosugars, on several cell lines, highlighted, for some of them, their antiproliferative and anti migration and invasion properties at nanomolar concentration.

We investigated the biological effects of new synthesized bisphosphonates (BPs) on HuH7 hepatocarcinoma cells. BPs containing p-bromophenyl (R1 = p-Br, Ph, 2) in their side chain were the more potent to inhibit HuH7 cell viability. In addition, phenyl diesterified analogues (R2 = R3 = Ph, 2a) were more potent than methyl (R2 = R3 = Me, 2b) or non-esterified BPs (2) inducing more necrosis suggesting that they better entered into cells. Phosphodiesterase inhibitor (IBMX) reversed the effect of the esterified BPs and not that of non-esterified ones suggesting role of cell phosphodiesterases to release active BPs. BP analogues inhibited HuH7 cell migration but esterified ones had no effect on invasion due to the hiding of phosphonic groups. All together, these results indicated the therapeutic interest of these new BP prodrugs.

International audience; Zosterin, an apiose-rich pectic polysaccharide, was extracted and purified from the sea grass Zostera marina. Structural studies conducted by gas chromatography and NMR spectroscopy on a purified zosterin fraction (AGU) revealed a typical apiogalacturonan structure comprising an α-1,4-d- galactopyranosyluronan backbone substituted by 1,2-linked apiofuranose oligosaccharides and single apiose residues. The average molecular mass of AGU was estimated to be about 4100 Da with a low polydispersity. AGU inhibited proliferation of A431 human epidermoid carcinoma cells with an approximate IC50 value of 3 μg/mL (0.7 μM). In addition, AGU inhibited A431 cell migration and invasion. Preliminary experiments showed that inhibition of metalloproteases expression could play a role in these antimigration and anti-invasive properties. Autohydrolysis of AGU, which eliminated apiose and oligo-apiose substituents, led to a virtual disappearance of cytotoxic properties, thus suggesting a direct structure-function relationship with the apiose-rich hairy region of AGU.

The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.

International audience; The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.

International audience; The synthesis and biological activity of a novel DNA cross-linking antitumor agent is presented. The new alkylating agent significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.

International audience; The capsular polysaccharide produced by the thermophilic blue green alga/cyanobacterium Mastigocladus laminosus was tested for its cytotoxic activity against the A431 human epidermoid carcinoma cell line. This polysaccharide inhibited the proliferation of A431 cells in a dose-dependent manner with an IC (50) value of 50 microg mL (-1). In addition, this polysaccharide strongly inhibited A431 cell migration and invasion. Preliminary experiments showing that secretion of metalloproteinases MMP2 and MMP9 by A431 tumour cells was inhibited by this polysaccharide suggest that this mechanism of action could play a role in its anti-migration and anti-invasive properties. Acid hydrolysis of the polysaccharide produced specific oligosaccharides which conserved - at similar concentrations - their cytotoxic, anti-migration and anti-invasion properties; in this case, the mechanism of action was nevertheless uncorrelated to the decrease of metalloproteinase expression.