2. Academic Validation
  3. Pyr3 inhibits cell viability and PKCα activity to suppress migration in human bladder cancer cells

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

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: doc20283@mail.ndmctsgh.edu.tw.
  • 5 Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: ychen0523@mail.ndmctsgh.edu.tw.
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-108465
    99.90%, TRPC3 Channel Inhibitor