Induction of Cell Death by Betulinic Acid through Induction of Apoptosis and Inhibition of Autophagic Flux in Microglia BV-2 Cells
| Autor: | Juneyoung Jung, Jeongbin Seo, Joungmok Kim, Jeong Hee Kim, Dae Sik Jang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pharmacology Programmed cell death Microglia Poly ADP ribose polymerase Autophagy Apoptosis Biological activity Betulinic acid Biochemistry Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology medicine.anatomical_structure chemistry Drug Discovery medicine Microglia BV-2 cell Molecular Medicine Cytotoxic T cell Original Article |
| Zdroj: | Biomolecules & Therapeutics |
| ISSN: | 1976-9148 2005-4483 |
| DOI: | 10.4062/biomolther.2016.255 |
| Popis: | 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 IC₅₀ of approximately 2.0 µM. 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. |
| Databáze: | OpenAIRE |
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