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

Research output: Contribution to journalArticlepeer-review

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 (US)
Pages (from-to)239-259
Number of pages21
JournalCancer Letters
Volume344
Issue number2
DOIs
StatePublished - Mar 28 2014
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Non-small-cell lung cancer
  • PI3K/Akt/mTOR
  • Plumbagin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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