Interaction of colon cancer cells with glycoconjugates triggers complex changes in gene expression, glucose transporters and cell invasion

Mol Med Rep. 2018 Apr;17(4):5508-5517. doi: 10.3892/mmr.2018.8490. Epub 2018 Jan 25.

Abstract

Glycan metabolism balance is critical for cell prosperity, and macromolecule glycosylation is essential for cell communication, signaling and survival. Thus, glycotherapy may be a potential cancer treatment. The aim of the present study was to determine whether combined synthetic glycoconjugates (GCs) induce changes in gene expression that alter the survival of colon cancer cells. The current study evaluated the effect of the GCs N‑acetyl‑D‑glucosamine modified polyamidoamine dendrimer and calix[4]arene scaffold on cancer cell proliferation, apoptosis, invasion and sensitivity to immune cell‑mediated killing. Using reverse transcription‑quantitative polymerase chain reaction, the expression of genes involved in the aforementioned processes was measured. It was determined that GCs reduce the expression of the glucosaminyltransferases Mgat3 and Mgat5 responsible for surface glycosylation and employed components of the Wnt signaling pathway Wnt2B and Wnt9B. In addition, the calix[4]arene‑based GC reduced cell colony formation; this was accompanied by the downregulation of the metalloproteinase Mmp3. By contrast, the dendrimer‑based GC affected the expression of the glucose transporter components Sglt1 and Egfr1. Therefore, to the best of our knowledge, the present study is the first to reveal that N‑acetyl‑D‑glucosamine‑dendrimer/calix[4]arene GCs alter mRNA expression in a comprehensive way, resulting in the reduced malignant phenotype of the colon cancer cell line HT‑29.

MeSH terms

  • Apoptosis / genetics
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / drug effects
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glucose / metabolism
  • Glucose Transport Proteins, Facilitative / genetics*
  • Glycoconjugates / pharmacology*
  • HT29 Cells
  • Humans
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Transcriptome
  • Tumor Stem Cell Assay

Substances

  • Cell Adhesion Molecules
  • Glucose Transport Proteins, Facilitative
  • Glycoconjugates
  • Glucose