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A plant triterpenoid, avicin D, induces autophagy by activation of AMP-activated protein kinase.
- Source :
-
Cell Death & Differentiation . Nov2007, Vol. 14 Issue 11, p1948-1957. 10p. 6 Graphs. - Publication Year :
- 2007
-
Abstract
- Avicins, a family of plant triterpene electrophiles, can trigger apoptosis-associated tumor cell death, and suppress chemical-induced carcinogenesis by its anti-inflammatory, anti-mutagenic, and antioxidant properties. Here, we show that tumor cells treated with benzyloxycarbonylvalyl-alanyl–aspartic acid (O-methyl)–fluoro-methylketone, an apoptosis inhibitor, and Bax−/−Bak−/− apoptosis-resistant cells can still undergo cell death in response to avicin D treatment. We demonstrate that this non-apoptotic cell death is mediated by autophagy, which can be suppressed by chloroquine, an autophagy inhibitor, and by specific knockdown of autophagy-related gene-5 (Atg5) and Atg7. Avicin D decreases cellular ATP levels, stimulates the activation of AMP-activated protein kinase (AMPK), and inhibits mammalian target of rapamycin (mTOR) and S6 kinase activity. Suppression of AMPK by compound C and dominant-negative AMPK decreases avicin D-induced autophagic cell death. Furthermore, avicin D-induced autophagic cell death can be abrogated by knockdown of tuberous sclerosis complex 2 (TSC2), a key mediator linking AMPK to mTOR inhibition, suggesting that AMPK activation is a crucial event targeted by avicin D. These findings indicate the therapeutic potential of avicins by triggering autophagic cell death.Cell Death and Differentiation (2007) 14, 1948–1957; doi:10.1038/sj.cdd.4402207; published online 10 August 2007 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 14
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 27076076
- Full Text :
- https://doi.org/10.1038/sj.cdd.4402207