Preparation, characterization and in vitro anti-metastasis activity of glucan derivatives

Abstract

Abstract Four derivatives (PSC, PSC1, PMC and PMC1) with different substitution were prepared from β-(1→3)- d -glucan or carboxymethyl glucan using modified Wolfrom's method and characterized by homogeneity analysis, molecular weight analysis and elemental analysis. The structure of PSC was confirmed by FTIR and 13C NMR. FTIR spectrum of PSC showed the characteristic absorptions of sulfate ester bonds at 807 cm−1 and 1210 cm−1. 13C NMR spectrum indicated the relatively high substitution degree at C-6 position. The heparanase inhibitory activities of four derivatives were predicted by docking to a homology model of heparanase. The result of the heparanase assay in vitro supported the computer prediction. Of these, PSC (8,000 Da, DS = 2.6) showed the high inhibitory activity. In further investigations, it was found that PSC remarkably inhibited the bFGF induced migration of HUVECs and MDA-MB-435. The result of the Western blotting revealed that PSC blocked basic fibroblast growth factor (bFGF) signal transduction pathway by decreasing the phosphorylation of ERK 1/2 and JNK.