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Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells
journal contribution
posted on 2014-03-28, 00:00 authored by Y C Li, S M He, Z X He, M Li, Y Yang, J X Pang, X Zhang, K Chow, Q Zhou, Wei DuanWei Duan, Z W Zhou, T Yang, G H Huang, A Liu, J X Qiu, J P Liu, S F ZhouPlumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines. PLB dose-dependently induces autophagy through inhibition of PI3K/Akt/mTOR pathway as indicated by reduced phosphorylation of Akt and mTOR. Inhibition or induction of autophagy enhances PLB-induced apoptosis. There is crosstalk between PLB-induced apoptosis and autophagy. These findings indicate that PLB initiates both apoptosis and autophagy in NSCLC cells through coordinated pathways.
History
Journal
Cancer LettersVolume
344Issue
2Pagination
239 - 259Publisher
Elsevier IrelandLocation
Shannon, County Clare, IrelandPublisher DOI
ISSN
1872-7980eISSN
1872-7980Language
EnglishPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2014, ElsevierUsage metrics
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No categories selectedKeywords
ApoptosisAutophagyNon-small-cell lung cancerPI3K\/Akt\/mTORPlumbaginCarcinoma, Non-Small-Cell LungCell Line, TumorHumansLung NeoplasmsMAP Kinase Signaling SystemNaphthoquinonesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesScience & TechnologyLife Sciences & BiomedicineOncologyNF-KAPPA-BCYTOCHROME-CCYCLE ARRESTIN-VITROSIGNALING PATHWAYBONE METASTASISP53BREASTPHOSPHORYLATIONEXPRESSION
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