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

Carbohydr Polym. 2017 Jul 1:167:229-239. doi: 10.1016/j.carbpol.2017.02.104. Epub 2017 Mar 6.

Abstract

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: 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.

Keywords: Antrodia cinnamomea; Lung cancer; Slug; Sulfated polysaccharides; Transforming growth factor β receptors (TGFRs).

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antrodia / chemistry*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival
  • Focal Adhesion Kinase 1 / metabolism*
  • Galactans / chemistry*
  • Glucans / chemistry*
  • Humans
  • Lung Neoplasms / pathology
  • Polysaccharides, Bacterial / chemistry*
  • Signal Transduction
  • Snail Family Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism*

Substances

  • Antineoplastic Agents
  • Galactans
  • Glucans
  • Polysaccharides, Bacterial
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta
  • galactoglucan
  • Focal Adhesion Kinase 1
  • PTK2 protein, human