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

• Published in: Carbohydrate polymers 2017-07, Vol.167, p.229-239
• Main Authors: Lu, Mei-Kuang, Lin, Tung-Yi, Hu, Chun-Hao, Chao, Chi-Hsein, Chang, Chia-Chuan, Hsu, Hsien-Yeh
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antrodia - chemistry; Antrodia cinnamomea; Apoptosis; Cell Line, Tumor; Cell Survival; Focal Adhesion Kinase 1 - metabolism; Galactans - chemistry; Glucans - chemistry; Humans; Lung cancer; Lung Neoplasms - pathology; Polysaccharides, Bacterial - chemistry; Signal Transduction; Slug; Snail Family Transcription Factors - metabolism; Sulfated polysaccharides; Transforming Growth Factor beta - metabolism; Transforming growth factor β receptors (TGFRs)
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2017.02.104

A sulfated 1,4-β-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 (1H, 13C 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 4C1 chair form. The sulfate substitutions were suggested to be on the C-2 and C-3 positions, resulting in the following structure: [Display omitted] B86-III inhibited the viability of H1975 lung cancer cells via cell apoptosis, including the activation of caspase 3 and PARP. Transforming growth factor β 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.