Plumbagin induces apoptotic and autophagic cell death through inhibition of the PI3K/Akt/mTOR pathway in human non-small cell lung cancer cells

Abstract Plumbagin (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 ce...

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Veröffentlicht in:Cancer letters 2014-03, Vol.344 (2), p.239-259
Hauptverfasser: Li, Yan-Cong, He, Shu-Ming, He, Zhi-Xu, Li, Minghua, Yang, Yinxue, Pang, Jian-Xin, Zhang, Xueji, Chow, Kevin, Zhou, Qingyu, Duan, Wei, Zhou, Zhi-Wei, Yang, Tianxin, Huang, Gui-Hua, Liu, Aibing, Qiu, Jia-Xuan, Liu, Jun-Ping, Zhou, Shu-Feng
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Sprache:eng
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Zusammenfassung:Abstract Plumbagin (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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2013.11.001