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http://dx.doi.org/10.4062/biomolther.2016.255

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)
Publication Information
Biomolecules & Therapeutics / v.25, no.6, 2017 , pp. 618-624 More about this Journal
Abstract
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.
Keywords
Betulinic acid; Apoptosis; Autophagy; Microglia BV-2 cell;
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