Induction of Cell Death by Betulinic Acid through Induction of Apoptosis and Inhibition of Autophagic Flux in Microglia BV-2 Cells

  • Seo, Jeongbin (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Jung, Juneyoung (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Jang, Dae Sik (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Kim, Joungmok (Department of Oral Biochemistry and Molecular Biology, School of Dentistry, Kyung Hee University) ;
  • Kim, Jeong Hee (Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University)
  • Received : 2016.11.15
  • Accepted : 2016.12.27
  • Published : 2017.11.01


Betulinic acid (BA), a natural pentacyclic triterpene found in many medicinal plants is known to have various biological activity including tumor suppression and anti-inflammatory effects. In this study, the cell-death induction effect of BA was investigated in BV-2 microglia cells. BA was cytotoxic to BV-2 cells with $IC_{50}$ of approximately $2.0{\mu}M$. Treatment of BA resulted in a dose-dependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content. BA treatment triggered apoptosis by decreasing Bcl-2 levels, activation of capase-3 protease and cleavage of PARP. In addition, BA treatment induced the accumulation of p62 and the increase in conversion of LC3-I to LC3-II, which are important autophagic flux monitoring markers. The increase in LC3-II indicates that BA treatment induced autophagosome formation, however, accumulation of p62 represents that the downstream autophagy pathway is blocked. It is demonstrated that BA induced cell death of BV-2 cells by inducing apoptosis and inhibiting autophagic flux. These data may provide important new information towards understanding the mechanisms by which BA induce cell death in microglia BV-2 cells.



Supported by : National Research Foundation of Korea


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