Berberine Promotes Antiproliferative Effects of Epirubicin in T24 Bladder Cancer Cells by Enhancing Apoptosis and Cell Cycle Arrest

Int J Clin Pharmacol Ther. 2017 Jan;55(1):32-40. doi: 10.5414/CP202534.


Objective: The present study was aimed to observe the effect of berberine (Ber) on epirubicin (EPI)-induced growth inhibition, apoptosis, and cell cycle arrest in T24 bladder cancer cells.

Methods: The cancer cells were exposed to EPI, with or without different concentrations of Ber. The viability of the cancer cells was measured by cell counting Kit-8, the apoptosis was determined by Hoechst 33258 staining and the expression of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, and P53 proteins were detected by Western blot assay. In addition, cell cycle arrest and the production of reactive oxygen species (ROS) were also measured.

Results: We found that Ber enhanced the inhibitory effect of EPI on the viability of T24 cells and promoted EPI-induced cell cycle arrest at G0/G1 and apoptosis in T24 cells. EPI increased the expression of cleaved caspase-3, cleaved caspase-9, Bax, P53, and P21 proteins, all of which were enhanced by treatment with Ber. In contrast, Ber exposure further decreased the expression of Bcl-2 in EPI-treated T24 cells. Furthermore, we also demonstrated that Ber significantly increased ROS production in EPI-treated T24 cells.

Conclusions: These data indicate that Ber enhances the antiproliferative effects of EPI in bladder cancer cells by promoting apoptosis and cell cycle arrest. .

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Berberine / administration & dosage
  • Berberine / pharmacology*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Drug Synergism
  • Epirubicin / administration & dosage
  • Epirubicin / pharmacology*
  • Humans
  • Reactive Oxygen Species / metabolism
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*


  • Antibiotics, Antineoplastic
  • Reactive Oxygen Species
  • Berberine
  • Epirubicin
  • Caspase 3