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Deoxypodophyllotoxin induces cytoprotective autophagy against apoptosis via inhibition of PI3K/AKT/mTOR pathway in osteosarcoma U2OS cells

Authors
Kim, SH | Son, KM | Kim, KY | Yu, SN | Park, SG | Kim, YW | Nam, HW | Suh, JT | Ji, JH  | Ahn, SC
Citation
Pharmacological reports : PR, 69(5). : 878-884, 2017
Journal Title
Pharmacological reports : PR
ISSN
1734-1140null
Abstract
BACKGROUND: A natural compound deoxypodophyllotoxin (DPT) possesses potent anti-proliferative and anti-tumor properties on several cancer types. It triggers cell cycle arrest followed by apoptosis through various cellular processes. However, it is limited to the action mechanism of DPT-mediated cell death modes via apoptosis and autophagy.
METHODS: Cell viability assay, morphological changes, annexin-V/propidium iodide (PI) assay, reactive oxygen species (ROS), acridine orange staining, and Western blot analyses were evaluated.
RESULTS: We demonstrated that DPT induced both apoptosis and autophagy via production of mitochondrial reactive oxygen species (ROS). DPT suppressed the PI3K/AKT/mTOR signaling cascades to lead autophagy process, resulting from conversion of light chain 3-I (LC3-I) into LC3-II and acidic vesicular organelles (AVOs) formation. Even if DPT-induced ROS were occurred in both apoptosis and autophagy, inhibition of ROS generation enhanced cell viability. Otherwise, 3-methyladeine (3-MA) impeding on autophagy accelerated an apoptotic response caused by DPT. Therefore, these findings suggest that DPT triggers cytoprotective autophagy against cytotoxic apoptosis.
CONCLUSION: Autophagy is required for cell survival by inhibition of apoptosis through down-regulation of PI3K/AKT/mTOR pathway against DPT-induced apoptosis in U2OS cells.
Keywords
DOI
10.1016/j.pharep.2017.04.007
PMID
28623712
Appears in Collections:
Journal Papers > Research Organization > Genomic Instability Research Center
Ajou Authors
지, 재훈
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