title: Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells.
abstract: BACKGROUND
  Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, is recommended as the first-line anti-malarial drug with low toxicity. DHA has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways, although the molecular mechanisms are not well understood.
  
  
  METHODS
  In this study, cell counting kit (CCK-8) assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. Collapse of mitochondrial transmembrane potential (DeltaPsim) was measured by dynamic detection under a laser scanning confocal microscope and flow cytometry analysis using Rhodamine123. Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis.
  
  
  RESULTS
  Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of DeltaPsim and the activation of caspase-3.
  
  
  CONCLUSIONS
  These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. Our work may provide evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of lung adenocarcinoma.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou 510631, PR China. superchristie@sina.com
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Lu
authors.forename: Tong-Sheng
authors.initials: TS
authors.lastname: Chen
authors.forename: Jun-Le
authors.initials: JL
authors.lastname: Qu
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Pan
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Xun-Bin
authors.initials: XB
authors.lastname: Wei
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000962:Antimalarials / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D037621:Artemisinins / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects*; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008168:Lung / Q000166:cytology*; D008175:Lung Neoplasms / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000962:Antimalarials; D037621:Artemisinins; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C039060:artenimol; D053148:Caspase 3