Bitter Taste Receptor Agonists Induce Apoptosis in Papillary Thyroid Cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Papillary thyroid carcinoma (PTC) is the most prevalent thyroid malignancy, characterized by a significant recurrence rate.
• Bitter taste receptors (T2Rs) and their genes (TAS2Rs) are implicated in regulating cell survival within solid tumors.
• The expression and functional role of T2Rs in PTC cells remain largely unexplored.

Purpose of the Study:

• To investigate the expression of T2Rs in human PTC cell lines.
• To determine the functional effects of bitter agonist activation on PTC cell viability and apoptosis.
• To explore the correlation between T2R expression and patient survival outcomes in PTC.

Main Methods:

• Analysis of T2R gene and protein expression in three PTC cell lines (MDA-T32, MDA-T68, MDA-T85) using RT-qPCR and immunofluorescence.
• Measurement of intracellular calcium responses to bitter agonists via live cell imaging.
• Assessment of cell viability and apoptosis using crystal violet staining and caspase 3/7 activation assays.
• Correlation analysis between TAS2R14 expression and patient progression-free survival.

Main Results:

• TAS2R14 was found to be highly expressed across all examined PTC cell lines.
• Activation by five distinct bitter agonists elicited significant calcium responses in both cytoplasmic and mitochondrial compartments.
• Exposure to bitter agonists markedly reduced cell viability and induced apoptosis in PTC cells.
• A significant positive correlation was observed between higher TAS2R14 expression and improved progression-free survival in PTC patients (p < 0.05).

Conclusions:

• Activation of T2Rs by bitter agonists triggers apoptosis in PTC cells.
• Elevated T2R expression is associated with enhanced survival outcomes in patients with thyroid cancer.
• These findings highlight the potential therapeutic utility of T2R agonists in managing thyroid cancer.