title: Withaferin A induces mitochondrial-dependent apoptosis in non-small cell lung cancer cells via generation of reactive oxygen species.
abstract: OBJECTIVE
  Withaferin A (WA) is a bioactive lactone, isolated from natural sources, mainly found in Withania somnifera, and was known to be highly effective against a variety of tumor cells both in vitro and in vivo. Accumulating experimental evidence suggests the involvement of reactive oxygen species (ROS) in WA-mediated cytotoxicity against cancer cells. Hence, the purpose of this study was to investigate the effect of WA in non-small cell lung cancer (NSCLC) cells and also the role of ROC in WA-mediated cytotoxicity.
  
  
  METHODS
  In the present study we investigated the cytotoxic potential of WA against NSCLC cell line A549 and also highlighted the mechanism of cytotoxicity of this compound. Non-carcinoma WI-38 and PBMC cell lines were used as controls.
  
  
  RESULTS
  WA treatment resulted in a dose-dependent cytotoxicity in A549 cells, while the non-carcinoma cells WI-38 and PBMC were unaffected. Further experimental approaches revealed that ROS plays a major role in WAinduced apoptosis in NSCLC cells.
  
  
  CONCLUSIONS
  WA induces oxidative damage to NSCLC cells with minimum toxicity to normal cells.
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, 100853, P.R.China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Tian
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D054358:Withanolides / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D054358:Withanolides; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; C009684:withaferin A