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

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dc.contributor.authorKim, SH-
dc.contributor.authorSon, KM-
dc.contributor.authorKim, KY-
dc.contributor.authorYu, SN-
dc.contributor.authorPark, SG-
dc.contributor.authorKim, YW-
dc.contributor.authorNam, HW-
dc.contributor.authorSuh, JT-
dc.contributor.authorJi, JH-
dc.contributor.authorAhn, SC-
dc.date.accessioned2018-08-24T01:48:53Z-
dc.date.available2018-08-24T01:48:53Z-
dc.date.issued2017-
dc.identifier.issn1734-1140-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/15908-
dc.description.abstractBACKGROUND: 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.
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dc.formatapplication/pdf-
dc.language.isoen-
dc.titleDeoxypodophyllotoxin induces cytoprotective autophagy against apoptosis via inhibition of PI3K/AKT/mTOR pathway in osteosarcoma U2OS cells-
dc.typeArticle-
dc.identifier.pmid28623712-
dc.subject.keywordApoptosis-
dc.subject.keywordDPT-
dc.subject.keywordDeoxypodophyllotoxin-
dc.subject.keywordROS-
dc.subject.keywordReactive oxygen species-
dc.contributor.affiliatedAuthor지, 재훈-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.pharep.2017.04.007-
dc.citation.titlePharmacological reports : PR-
dc.citation.volume69-
dc.citation.number5-
dc.citation.date2017-
dc.citation.startPage878-
dc.citation.endPage884-
dc.identifier.bibliographicCitationPharmacological reports : PR, 69(5). : 878-884, 2017-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissnnull-
dc.relation.journalidJ017341140-
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Journal Papers > Research Organization > Genomic Instability Research Center
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