Dendropanoxide Induces Autophagy through ERK1/2 Activation in MG-63 Human Osteosarcoma Cells and Autophagy Inhibition Enhances Dendropanoxide-Induced Apoptosisopen access
- Authors
- Lee, JW[Lee, Ji-Won]; Kim, KS[Kim, Kyoung-Sook]; An, HK[An, Hyun-Kyu]; Kim, CH[Kim, Cheorl-Ho]; Moon, HI[Moon, Hyung-In]; Lee, YC[Lee, Young-Choon]
- Issue Date
- 17-Dec-2013
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.8, no.12
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 8
- Number
- 12
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/58198
- DOI
- 10.1371/journal.pone.0083611
- ISSN
- 1932-6203
- Abstract
- Anticancer effects of dendropanoxide (DP) newly isolated from leaves and stem of Dendropanax morbifera Leveille were firstly investigated in this study. DP inhibited cell proliferation and induced apoptosis in dose-and time-dependent manner in MG-63 human osteosarcoma cells, which was dependent on the release of cytochrome c to the cytosol and the activation of caspases. Moreover, the DP-treated cells exhibited autophagy, as characterized by the punctuate patterns of microtubule-associated protein 1 light chain 3 (LC3) by confocal microscopy and the appearance of autophagic vacuoles by MDC staining. The expression levels of ATG7, Beclin-1 and LC3-II were also increased by DP treatment. Inhibition of autophagy by 3-methyladenine (3-MA) and wortmannin (Wort) significantly enhanced DP-induced apoptosis. DP treatment also caused a time-dependent increase in protein levels of extracellular signal-regulated kinase 1 and 2 (ERK1/2), and inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased DP-induced autophagy that was accompanied by an increased apoptosis and a decreased cell viability. These results indicate a cytoprotective function of autophagy against DP-induced apoptosis and suggest that the combination of DP treatment with autophagy inhibition may be a promising strategy for human osteosarcoma control. Taken together, this study demonstrated for the first time that DP could induce autophagy through ERK1/2 activation in human osteosarcoma cells and autophagy inhibition enhanced DP-induced apoptosis.
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Collections - Science > Department of Biological Science > 1. Journal Articles
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