Chemical identification of a sulfated glucan from Antrodia cinnamomea and its anti-cancer functions via inhibition of EGFR and mTOR activity

Carbohydr Polym. 2018 Dec 15:202:536-544. doi: 10.1016/j.carbpol.2018.09.009. Epub 2018 Sep 6.

Abstract

Antrodia cinnamomea is a polyporaceous medicinal and native fungus in Taiwan. In this study, we found that AC-SPS-F3, a sulfated glucan from A. cinnamomea, reduced lung cancer cell viability via inhibition of EGFR and mTOR activity. The co-administration of AC-SPS-F3 and cisplatin synergistically inhibited lung cancer cell viability. We identified AC-SPS-F3 was a sulfated β-(1→4)-d-glucan with two long 1,6-branches in each repeat unit. The FT-IR absorption at 1341 cm-1 and 887 cm-1 confirmed the existence of sulfates. The proposed repeat unit of AC-SPS-F3, including the types of main skeleton and side chains, as well as the position of the minor galactopyranosyl and mannopyranosyl residues, were proposed according to the 1D and 2D NMR spectra, shown as follows: The features for the proposed repeat unit of AC-SPS-F3 included two long β-(1→6)-Glcp branches, a very high ratio of sulfate substitution, and partial 2-O and 4-O substituents evenly distributed on the β-(1→6)-Glcp branches. The present study is first to characterize the highly branched sulfated polysaccharides and elucidates its anti-cancer functions.

Keywords: Antrodia cinnamomea; FT-IR; Lung cancer; NMR; Sulfated polysaccharides; Synergistic effect.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Antrodia / chemistry*
  • Carbohydrate Conformation
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Glucans / chemistry
  • Glucans / isolation & purification
  • Glucans / pharmacology*
  • Humans
  • Sulfates / chemistry
  • Sulfates / isolation & purification
  • Sulfates / pharmacology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Glucans
  • Sulfates
  • MTOR protein, human
  • EGFR protein, human
  • ErbB Receptors
  • TOR Serine-Threonine Kinases