Characterization of a sulfated galactoglucan from Antrodia cinnamomea and its anticancer mechanism via TGFβ/FAK/Slug axis suppression

A sulfated 1,4-beta-D-galactoglucan (B86-III) with 1,6-branches was isolated and identified from Antrodia cinnamomea. The repeating unit of B86-III was proposed based on one-dimensional 1D (H-1, C-13 and DEPT-135) and 2D (DQF-COSY, TOCSY, HSQC and HMBC) NMR spectra. The conformation of the sugars was hypothesized to be a rare boat form instead of a C-4(1) chair form. The sulfate substitutions were suggested to be on the C-2 and C-3 positions, resulting in the following structure: [GRAPHICS] B86-III inhibited the viability of H1975 lung cancer cells via cell apoptosis, including the activation of caspase 3 and PARP. Transforming growth factor beta receptor (TGFR) and its downstream signaling FAK and Slug are involved in lung tumorigenesis. B86-III downregulated TGFR I protein levels and inhibited FAK phosphorylation, resulting in inhibition of Slug expression and migration. This study is the first to characterize sulfated polysaccharides with a rare boat-form conformation and identify the mechanism of inhibition lung cancer cell. (C) 2017 Elsevier Ltd. All rights reserved.