The effect of ICRT-3 on Wnt signaling pathway in head and neck cancer

J Cell Biochem. 2019 Jan;120(1):380-395. doi: 10.1002/jcb.27393. Epub 2018 Aug 26.

Abstract

The effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of β-catenin responsive transcription (ICRT-3) blocks the Wnt signaling pathway by binding to β-catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT-3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer. The effect of this compound on cytotoxicity and cell viability in FaDu and HNCSC line was assessed by using the water-soluble tetrazolium salt-1 method. The effect of ICRT-3 on apoptosis was detected by using Annexin V and caspase-3, caspase-9 kit, on cell cycle progression by cycle test plus DNA reagent kit, on gene expression by dual luciferase reporter assay, and on migration activity by wound healing assay in both cell lines. ICRT-3 was determined to have cytotoxic and apoptotic effect in both cell lines. In addition, it was also found that the administration of ICRT-3 caused cell cycle arrest and significant decrease in gene expression level and migration ability of the cells.

Keywords: Wnt signaling pathway; apoptosis; cell cycle; head and neck cancer stem cell (HNCSC); hypopharynx cancer; inhibitor of β-catenin responsive transcription (ICRT-3); β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / pathology
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cytotoxins / metabolism
  • Cytotoxins / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Hypopharyngeal Neoplasms / pathology
  • Inhibitory Concentration 50
  • Lymphoid Enhancer-Binding Factor 1 / metabolism
  • Neoplastic Stem Cells / metabolism*
  • Oxazoles / metabolism
  • Oxazoles / pharmacology*
  • Signal Transduction / drug effects
  • Transcription Factor 4 / metabolism
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • Cytotoxins
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Oxazoles
  • TCF4 protein, human
  • Transcription Factor 4
  • beta Catenin
  • iCRT3 compound
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9