Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway

Neurochem Res. 2017 Apr;42(4):1130-1140. doi: 10.1007/s11064-016-2147-y. Epub 2017 Jan 25.


Betulinic acid (BA), a pentacyclic triterpene of natural origin, has been demonstrated to have varied biologic activities including anti-viral, anti-inflammatory, and anti-malarial effects; it has also been found to induce apoptosis in many types of cancer. However, little is known about the effect of BA on normal cells. In this study, the effects of BA on normal neuronal cell apoptosis and the mechanisms involved were studied using differentiated PC12 cells as a model. Treatment with 50 μM BA for 24 h apparently induced PC12 cell apoptosis. In the early stage of apoptosis, the level of intracellular reactive oxygen species (ROS) increased. Afterwards, the loss of the mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-3 occurred. Treatment with antioxidants could significantly reduce BA-induced PC12 cell apoptosis. In conclusion, we report for the first time that BA induced the mitochondrial apoptotic pathway in differentiated PC12 cells through ROS.

Keywords: Apoptosis; BA; Mitochondrial; PC12 cells; ROS.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Betulinic Acid
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • PC12 Cells
  • Pentacyclic Triterpenes
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Triterpenes / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • Pentacyclic Triterpenes
  • Reactive Oxygen Species
  • Triterpenes
  • Betulinic Acid