title: BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model.
abstract: BACKGROUND
  2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinolin-11-one (BPIQ) is a derivative from 6-arylindeno[1,2-c]quinoline. Our previous study showed the anti-cancer potential of BPIQ compared to its two analogues topotecan and irinotecan. In the study, the aim is to investigate the potency and the mechanism of BPIQ against lung cancer cells.
  
  
  METHODS
  Both in vitro and zebrafish xenograft model were performed to examine the anti-lung cancer effect of BPIQ. Flow cytometer-based assays were performed for detecting apoptosis and cell cycle distribution. Western blot assay was used for detecting the changes of apoptotic and cell cycle-associated proteins. siRNA knockdown assay was performed for confirming the apoptotic role of Bim.
  
  
  RESULTS
  Both in vitro and zebrafish xenograft model demonstrated the anti-lung cancer effect of BPIQ. BPIQ-induced proliferative inhibition of H1299 cells was achieved through the induction of G2/M-phase arrest and apoptosis. The results of Western blot showed that BPIQ-induced G2/M-phase arrest was associated with a marked decrease in the protein levels of cyclin B and cyclin-dependent kinase 1 (CDK1). The up-regulation of pro-apoptotic Bad, Bim and down-regulation of pro-survival XIAP and survivin was observed following BPIQ treatment.
  
  
  CONCLUSIONS
  BPIQ-induced anti-lung cancer is involved in mitochondrial apoptosis. BPIQ could be a promising anti-lung cancer drug for further applications.
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. cchiu@kmu.edu.tw.|Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan. cchiu@kmu.edu.tw.|Translational Research Center, Cancer Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. cchiu@kmu.edu.tw.|Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. cchiu@kmu.edu.tw.|Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. cchiu@kmu.edu.tw.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. d992050005@gmail.com.|Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. d992050005@gmail.com.
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Chou
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. bhchen@kmu.edu.tw.|Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. bhchen@kmu.edu.tw.
authors.forename: Bing-Hung
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. kfchang1231@gmail.com.
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. r920030@cc.kmu.edu.tw.|Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. r920030@cc.kmu.edu.tw.
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.affiliation: Department of Thoracic Surgery, Chi-Mei Medical Center, Tainan, 710, Taiwan. yaou.fong@msa.hinet.net.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fong
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, School of Medicine, National Cheng Kung University, Tainan, 701, Taiwan. tffu@mail.ncku.edu.tw.
authors.forename: Tzu-Fun
authors.initials: TF
authors.lastname: Fu
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. changhw@kmu.edu.tw.
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, 804, Taiwan. cywu@mail.nsysu.edu.tw.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. tsaieing@kmu.edu.tw.
authors.forename: Eing-Mei
authors.initials: EM
authors.lastname: Tsai
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. shreli@kmu.edu.tw.
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. yeloch@kmu.edu.tw.
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines; C037219:quinoline