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Updated: Jan 12, 2026

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
T2R5 Agonist Phendione Decreases Cell Viability and Induces Apoptosis in Head and Neck Squamous Cell Carcinoma
Sarah Sywanycz1, Brianna L Hill1, Zoey A Miller1
1Department of Otorhinolaryngology - Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract:
Bitter taste receptors (T2Rs), a family of G-protein-coupled receptors, are emerging as potential therapeutic targets in head and neck squamous cell carcinoma (HNSCC). Phendione, a known T2R5 agonist, has not been previously investigated in HNSCC. In this study, we show that phendione activates endogenously expressed T2R5 in HNSCC cells and ex vivo tumor samples, inducing sustained calcium responses, reducing cell viability, and promoting apoptosis through a T2R5-dependent mechanism. Analysis of The Cancer Genome Atlas data revealed that high T2R5 expression in HNSCC tumors correlates with improved long-term disease-specific survival, suggesting a potential tumor-suppressive role for T2R5. These findings highlight T2R5 as a promising therapeutic target in HNSCC and support further investigation of phendione or other T2R5 agonists as potential anticancer agents.
Insights
Phendione activates bitter taste receptor T2R5 in head and neck squamous cell carcinoma (HNSCC) cells, reducing viability and promoting apoptosis. High T2R5 expression correlates with better survival in HNSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Bitter taste receptors (T2Rs) are G-protein coupled receptors with emerging roles in cancer.
- Head and neck squamous cell carcinoma (HNSCC) is a significant global health challenge.
- The therapeutic potential of T2Rs in HNSCC remains largely unexplored.
Purpose of the Study:
- To investigate the role of T2R5 and its agonist phendione in HNSCC.
- To determine if phendione can modulate HNSCC cell behavior via T2R5 activation.
- To assess the clinical relevance of T2R5 expression in HNSCC patient survival.
Main Methods:
- Activation of T2R5 by phendione in HNSCC cell lines and ex vivo tumor samples.
- Measurement of intracellular calcium responses.
- Assessment of cell viability and apoptosis induction.
- Analysis of The Cancer Genome Atlas (TCGA) data for T2R5 expression and patient survival.
Main Results:
- Phendione activated endogenously expressed T2R5 in HNSCC cells and tumor samples.
- T2R5 activation by phendione induced sustained calcium responses.
- Phendione treatment reduced HNSCC cell viability and promoted apoptosis in a T2R5-dependent manner.
- High T2R5 expression in HNSCC tumors correlated with improved long-term disease-specific survival.
Conclusions:
- T2R5 is activated by phendione in HNSCC, leading to anti-cancer effects.
- T2R5 may play a tumor-suppressive role in HNSCC.
- T2R5 and its agonists like phendione represent promising therapeutic targets for HNSCC treatment.
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