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

Yan-Cong Li, Shu-Ming He, Zhi-Xu He, Minghua Li, Yinxue Yang, Jian-Xin Pang, Xueji Zhang, Kevin Chow, Qingyu Zhou, Wei Duan, Zhi-Wei Zhou, Tianxin Yang, Gui-Hua Huang, Aibing Liu, Jia-Xuan Qiu, Jun-Ping Liu, Shu-Feng Zhou

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120 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)239 - 259
Number of pages21
JournalCancer Letters
Volume344
Issue number2
DOIs
Publication statusPublished - 2014

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