Cordyceps sinensis polysaccharide inhibits colon cancer cells growth by inducing apoptosis and autophagy flux blockage via mTOR signaling

Carbohydr Polym. 2020 Jun 1:237:116113. doi: 10.1016/j.carbpol.2020.116113. Epub 2020 Mar 4.

Abstract

Cordyceps sinensis is thought to have anti-cancer effects, but its mechanisms remain elusive. In this study, we aimed to investigate the anti-cancer effect of Cordyceps sinensis polysaccharide (CSP) on human colon cancer cell line (HCT116) and its mechanism. Results indicated that CSP significantly inhibited the proliferation of HCT116 cells, increased autophagy and apoptosis, while blocked autophagy flux and lysosome formation. Further experiments showed that CSP decreased the expression of PI3K and phosphorylation level of AKT and mTOR, increased the expression of AMPKa and phosphorylation level of ULK1. In addition, repression of CSP-induced autophagy by bafilomycin (autophagy inhibitor) enhanced apoptosis and cell death of HCT116 cells. Hence, our findings suggested that CSP inhibited the proliferation of HCT116 cells by inducing apoptosis and autophagy flux blockage, which might be achieved through PI3K-AKT-mTOR and AMPK-mTOR-ULK1 signaling. CSP may be a potential therapeutic agent for colon cancer.

Keywords: 3-Methyladenine (PubChem CID: 135398661); Apoptosis; Autophagy; Bafilomycin A1 (PubChem CID: 6436223); Colon cancer cell; Cordyceps sinensis polysaccharide; Rapamycin (PubChem CID: 5284616); mTOR signaling.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology*
  • Cordyceps / chemistry*
  • HCT116 Cells
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polysaccharides / pharmacology*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Polysaccharides
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases