Cantharellus cibarius branched mannans inhibits colon cancer cells growth by interfering with signals transduction in NF-ĸB pathway

Int J Biol Macromol. 2019 Aug 1:134:770-780. doi: 10.1016/j.ijbiomac.2019.05.072. Epub 2019 May 15.

Abstract

In order to evaluate the therapeutic potential of polysaccharides obtained from the widely consumed Cantharellus cibarius mushroom on NF-ĸB pathway involved in cancer cells proliferation, survival, and metastasis, their antiproliferative and cytotoxic properties in human colon cancer cells LS180 and human colon epithelial cells CCD841 CoN were studied. BrdU and LDH assays results show that a branched mannan isolated from C. cibarius (CC2a) was selective against colon cancer cells, suppressing their proliferation and destroying membrane integrity but at the same time not adversely affecting colon epithelial cells. Results of Western blotting, immunofluorescence, RealTime PCR revealed that CC2a anticancer abilities were accompanied by disorders in signals transduction in NF-ĸB pathway in particular inhibition of IκBα degradation, attenuation of activated NF-κB phosphorylation and the subsequent decrease of NF-κB nuclear level as well as significant down-regulation of NF-κB target genes BAX, BCL2, CCND1, MMP9, MYC, BIRC5 and the corresponding proteins (except Bax). Furthermore, CC2a treatment of LS180 cells resulted in perturbation in G0/G and S phases of the cell cycle also associated with a marked increase of DNA fragmentation as well as inhibition of cancer cells motility. Obtained results indicated C. cibarius branched mannans as a new option in fighting with colon cancer.

MeSH terms

  • Agaricales / chemistry*
  • Animals
  • Apoptosis / drug effects
  • Biomarkers
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Fungal Polysaccharides / chemistry
  • Fungal Polysaccharides / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunohistochemistry
  • Mannans / chemistry
  • Mannans / isolation & purification
  • Mannans / pharmacology*
  • Mice
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects*
  • Spectroscopy, Fourier Transform Infrared
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers
  • Fungal Polysaccharides
  • Mannans
  • NF-kappa B