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.

PubMed

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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