Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines

Braz J Med Biol Res. 2015 Feb;48(2):111-9. doi: 10.1590/1414-431X20144293. Epub 2014 Dec 12.


Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects*
  • Berberine / therapeutic use*
  • Caspase 3 / drug effects
  • Caspase 7 / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Flow Cytometry
  • G1 Phase / drug effects*
  • Humans
  • Pancreatic Neoplasms / drug therapy*
  • Reactive Oxygen Species / metabolism*
  • Time Factors


  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Reactive Oxygen Species
  • Berberine
  • Deoxycytidine
  • gemcitabine
  • Caspase 3
  • Caspase 7