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The effect of ICRT-3 on Wnt signaling pathway in head and neck cancer
Fatma Sogutlu1, Cagla Kayabasi1, Besra Ozmen Yelken1
1Faculty of Medicine, Department of Medical Biology, Ege University, Bornova, Izmir, Turkey.
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.
Insights
The Wnt signaling inhibitor ICRT-3 effectively reduced head and neck cancer stem cell growth and migration. This compound demonstrated significant cytotoxic and apoptotic effects, offering a promising therapeutic strategy for head and neck cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant Wnt signaling is implicated in various cancers, but its role in head and neck cancer remains unclear.
- The Wnt signaling pathway, crucial for cancer development, involves β-catenin as a key coactivator.
- ICRT-3, an inhibitor of β-catenin responsive transcription, targets and blocks the Wnt signaling pathway.
Purpose of the Study:
- To investigate the therapeutic potential of ICRT-3 in head and neck cancer.
- To evaluate the effects of ICRT-3 on head and neck cancer stem cells (HNCSC) and hypopharynx cancer.
- To assess ICRT-3's impact on cytotoxicity, apoptosis, cell cycle, migration, and gene expression.
Main Methods:
- Cytotoxicity and cell viability assessed using water-soluble tetrazolium salt-1 assay.
- Apoptosis evaluated via Annexin V and caspase kits; cell cycle progression analyzed using DNA reagent kits.
- Gene expression measured by dual luciferase reporter assay; migration analyzed by wound healing assay.
Main Results:
- ICRT-3 exhibited significant cytotoxic and apoptotic effects in both FaDu and HNCSC lines.
- Administration of ICRT-3 led to cell cycle arrest in the tested cancer cells.
- ICRT-3 significantly reduced gene expression levels and migration ability of head and neck cancer cells.
Conclusions:
- ICRT-3 demonstrates potent anti-cancer properties against head and neck cancer stem cells and hypopharynx cancer.
- ICRT-3 effectively inhibits proliferation, induces apoptosis, and impedes migration, highlighting its therapeutic promise.
- Targeting the Wnt pathway with ICRT-3 represents a viable strategy for head and neck cancer treatment.
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