Sodium thiosulfate enhances production of polysaccharides and anticancer activities of sulfated polysaccharides in Antrodia cinnamomea

Carbohydr Polym. 2019 Jul 15:216:204-212. doi: 10.1016/j.carbpol.2019.04.017. Epub 2019 Apr 5.

Abstract

Sulfated polysaccharides (SPSs) are polysaccharides (PSs) with high sulfate functionalization and possess bioactivities. This study aimed to increase the sulfate content of SPSs in Antrodia cinnamomea through sulfate feeding. Feeding A. cinnamomea with sodium thiosulfate was found to increase yields of PSs and SPSs in A. cinnamomea. The SPSs thus obtained (ST-SPS) were further isolated, showing enhanced sulfate content of 2.5 mmol/g. Sodium thiosulfate induced changes in molecular weight from 320 kDa to 1342 kDa, and area percentage of low-molecular-weight ST-SPS (< 20 kDa) was decreased. Functional studies revealed that sodium thiosulfate increased the ST-SPS anticancer efficacy in cancer cells via inhibition of EGFR/AKT signaling. Moreover, the ST-SPS enhanced synergistically cisplatin-, gefitinib- and 5 FU-induced cytotoxic effects in lung cancer H1975 cells and colon cancer CT26 cells. This study is the first to demonstrate that sodium thiosulfate induced changes in properties of A. cinnamomea with the anticancer mechanisms of ST-SPS.

Keywords: Anticancer activity; Antrodia cinnamomea; Sodium thiosulfate; Sulfated polysaccharides.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antrodia / chemistry*
  • Antrodia / metabolism*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Synergism
  • ErbB Receptors / metabolism
  • Fluorouracil / pharmacology
  • Gefitinib / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Molecular Weight
  • Phosphorylation / drug effects
  • Polysaccharides / biosynthesis
  • Polysaccharides / chemistry
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Signal Transduction / drug effects
  • Sulfuric Acid Esters / chemistry
  • Sulfuric Acid Esters / isolation & purification
  • Sulfuric Acid Esters / metabolism
  • Sulfuric Acid Esters / pharmacology*
  • Thiosulfates / metabolism*

Substances

  • Antineoplastic Agents
  • Polysaccharides
  • Sulfuric Acid Esters
  • Thiosulfates
  • ErbB Receptors
  • sodium thiosulfate
  • Cisplatin
  • Gefitinib
  • Fluorouracil