title: Cyclosporine A induces apoptosis of human lung adenocarcinoma cells via caspase-dependent pathway.
abstract: BACKGROUND
  Aerosolized cyclosporine A (CsA) increases the local concentration of CsA in lung tissue and has proven to be an effective therapy for refractory rejection in lung transplant patients. However, the safety of high concentrations of CsA on tumour progression remains controversial.
  
  
  METHODS
  Human lung adenocarcinoma A549 cells were cultured with or without 1-3 μg/ml of CsA. The percentage of apoptotic cells was evaluated by Annexin V staining. The expressions of caspase-3, -9, -8 and cytochrome c were determined by Western blotting.
  
  
  RESULTS
  CsA therapy suppressed the growth of human lung cancer cells and increased the percentage of apoptotic cells compared with control cells. Western blot analysis revealed that CsA increased the levels of cytosolic cytochrome c and cleaved caspase-3 and -9, but not of cleaved caspase-8 in the lung cancer cells, suggesting that CsA-induced apoptosis is associated with the activation of caspase-3 and -9.
  
  
  CONCLUSIONS
  Our findings indicate that a high concentration of CsA has cytocidal effects through the caspase-3- and -9-dependent apoptotic pathway. This result shows that local administration of CsA does not increase the risk of secondary lung cancer.
authors: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamimachi, Itabashi-ku, Tokyo 173-8610, Japan.
authors: Maki
authors: M
authors: Sato
authors: Ichiro
authors: I
authors: Tsujino
authors: Makiko
authors: M
authors: Fukunaga
authors: Kenji
authors: K
authors: Mizumura
authors: Yasuhiro
authors: Y
authors: Gon
authors: Noriaki
authors: N
authors: Takahashi
authors: Shu
authors: S
authors: Hashimoto
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008928:Mitochondria / Q000201:enzymology
chemical_list: D007527:Isoenzymes; D016572:Cyclosporine; D045304:Cytochromes c; D020169:Caspases