title: Clozapine induces autophagic cell death in non-small cell lung cancer cells.
abstract: OBJECTIVE
  Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects.
  
  
  METHODS
  A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine.
  
  
  RESULTS
  Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7.
  
  
  CONCLUSIONS
  Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.
authors: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan.
authors: Yu-Chun
authors: YC
authors: Yin
authors: Chao-Cheng
authors: CC
authors: Lin
authors: Tzu-Ting
authors: TT
authors: Chen
authors: Jen-Yeu
authors: JY
authors: Chen
authors: Hui-Ju
authors: HJ
authors: Tsai
authors: Chia-Yu
authors: CY
authors: Wang
authors: Shiow-Yi
authors: SY
authors: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003024:Clozapine / Q000008:administration & dosage*; D006801:Humans; D018942:Macrolides / Q000008:administration & dosage; D034741:RNA, Small Interfering; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D018942:Macrolides; D034741:RNA, Small Interfering; C040929:bafilomycin A1; D003024:Clozapine