title: β-Elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells.
abstract: OBJECTIVE
  β-Elemene, a novel traditional Chinese medicine, has been shown to be effective against a wide range of tumours. In this study, the antitumour effect of β-elemene on human non-small-cell lung cancer (NSCLC) A549 cells and the mechanism involved have been investigated.
  
  
  METHODS
  Cell viability and apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein expression was assayed by Western blotting. Autophagy was evaluated under fluorescence microscopy and transmission electron microscopy.
  
  
  RESULTS
  β-Elemene inhibited the viability of A549 cells in a dose-dependent manner. This suppression of cell viability was due to the induction of apoptosis. Further study showed that β-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway, and at the same time it triggered a robust autophagy. The autophagy was characterized by the accumulation of punctate LC3 dots in the cytoplasm, morphological changes, and the increased levels of LC3-II as well as Atg5-Atg12 conjugated proteins. Inhibition of autophagy with chlorochine significantly enhanced the antitumour effect of β-elemene.
  
  
  CONCLUSIONS
  Our data indicated that β-elemene inhibited the activity of the PI3K/Akt/mTOR/p70S6K1 signalling pathway in human NSCLC A549 cells, which resulted in apoptosis as well as protective autophagy. A combination of β-elemene with autophagy inhibitor might be an effective therapeutic option for advanced NSCLC.
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Hu
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Qu
authors.forename: Ke-Zuo
authors.initials: KZ
authors.lastname: Hou
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008517:Phytotherapy / Q000379:methods; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D012717:Sesquiterpenes; C445979:beta-elemene