title: Autophagy Accompanied with Bisdemethoxycurcumin-induced Apoptosis in Non-small Cell Lung Cancer Cells.
abstract: OBJECTIVE
  To investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells.
  
  
  METHODS
  CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells.
  
  
  RESULTS
  BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells (SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened (SMO) and the transcription factor glioma-associated oncogene 1 (Gli1) expression. Furthermore, depletion of Gli1 by siRNA and cyclopamine (a specific SMO inhibitor) induced autophagy.
  
  
  CONCLUSIONS
  Aberrant activation of Hedgehog (Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.
authors.affiliation: Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jin Hong
authors.initials: JH
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: He Ping
authors.initials: HP
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiang Dong
authors.initials: XD
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hai Jing
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chun Lan
authors.initials: CL
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D036381:Diarylheptanoids; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; D036381:Diarylheptanoids; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000071676:Zinc Finger Protein GLI1; C034786:bisdemethoxycurcumin; D003474:Curcumin
keywords: Apoptosis; Autophagy; Bisdemethoxycurcumin; Hedgehog pathway; Non-small cell lung cancer