Pyr3 inhibits cell viability and PKCα activity to suppress migration in human bladder cancer cells

  • Eur J Pharmacol. 2025 Feb 5:988:177235. doi: 10.1016/j.ejphar.2024.177235.
Hui-Kung Ting  1 ,  Yi-Chien Dou  2 ,  Yi-Hsuan Lin  2 ,  Tzu-Min Chen  2 ,  Yu-Ling Tsai  3 ,  Wen-Chiuan Tsai  3 ,  Sheng-Tang Wu  4 ,  Ying Chen  5
Affiliations
  • 1. Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
  • 2. Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
  • 3. Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 4. Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; Division of Urology, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan. Electronic address: [email protected].
  • 5. Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: [email protected].
PMID: 39725132 DOI: 10.1016/j.ejphar.2024.177235
Abstract

Bladder Cancer, more prevalent in men, has high recurrence rates in non-muscle-invasive forms and is highly lethal upon metastasis in muscle-invasive cases. Transient receptor potential canonical channels (TRPCs), specifically TRPC3, play a role in calcium signaling, influencing Cancer cell behavior. This study examines the effects of Pyr3, a TRPC3 inhibitor, and TRPC3 knockdown on both muscle-invasive (T24) and non-muscle-invasive (RT4) bladder Cancer cells. Pyr3 treatment reduced cell viability, migration, adhesion, and calcium influx in these cells. Additionally, Pyr3 treatment and siTRPC3 downregulated protein kinase C alpha (PKCα), phospho-PKCα, and protein Phosphatase 2A (PP2A) levels. While PKC Activator phorbol 12-myristate 13-acetate (PMA) could not restore Pyr3-induced viability loss, it reversed the migration inhibition. In a xenograft model, Pyr3 suppressed T24 cell viability, Ki67, phospho-PKCα, PP2A and TRPC3 expression. These findings suggest that Pyr3 inhibits bladder Cancer cell migration through PKC signaling and holds potential as a therapeutic agent for bladder Cancer.

Keywords
Bladder cancer; Migration; PKCα; Pyr3; TRPC3.
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