Oridonin Suppresses Bladder Cancer Growth and Metastasis by Inducing S-Phase Arrest and Apoptosis

Wenqiang Sun1, Yongchao Li1, Menglong Xu1

  • 1The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Tarim University, Alar 843300, China.

Insights

Oridonin (ORI), a natural compound, effectively inhibits bladder cancer (BC) growth and metastasis. ORI induces cell cycle arrest and apoptosis, showing promise as a novel BC therapeutic agent with minimal toxicity.

Area of Science:

  • Oncology
  • Pharmacology
  • Natural Products Chemistry

Background:

  • Bladder cancer (BC) presents significant therapeutic challenges due to limited treatment options and high recurrence rates.
  • Oridonin (ORI), a natural diterpenoid from *Rabdosia* plants, shows potential anti-tumor effects, but its role in BC is not well understood.

Purpose of the Study:

  • To investigate the anti-cancer effects and underlying mechanisms of Oridonin (ORI) in bladder cancer (BC) models.
  • To evaluate ORI's efficacy and safety in vitro and in vivo for potential BC therapy.

Main Methods:

  • Utilized in vitro assays (proliferation, migration, invasion, cell-cycle, apoptosis) and in vivo xenograft models.
  • Integrated transcriptomic and proteomic analyses, Western blotting to elucidate molecular mechanisms.
  • Oridonin (ORI) treatment effects were assessed in 5637 and T24 bladder cancer cell lines and a 5637 xenograft mouse model.

Main Results:

  • Oridonin (ORI) dose- and time-dependently inhibited bladder cancer cell proliferation, migration, and invasion.
  • ORI induced significant S-phase arrest and promoted apoptosis and necrosis, evidenced by altered expression of apoptosis-related proteins (BAX, CASP3, BID, CYCS, BCL2).
  • In vivo, Oridonin (ORI) significantly suppressed tumor growth in a 5637 xenograft model without apparent toxicity.

Conclusions:

  • Oridonin (ORI) demonstrates significant anti-bladder cancer activity by inducing S-phase arrest and apoptosis.
  • ORI effectively inhibits BC growth and metastasis, suggesting its potential as a promising therapeutic candidate for bladder cancer.
  • The findings support further investigation of Oridonin (ORI) for clinical application in bladder cancer treatment.