title: Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE2.
abstract: OBJECTIVE
  83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis.
  
  
  METHODS
  A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2-derived prostaglandin E2(PGE2) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively.In vivoanti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450.
  
  
  RESULTS
  83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2-derived PGE2were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft.
  
  
  CONCLUSIONS
  The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Ivan Ho Yuen
authors.initials: IH
authors.lastname: Pun
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Dessy
authors.initials: D
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Sau Hing
authors.initials: SH
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Po Yee
authors.initials: PY
authors.lastname: Chung
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.affiliation: Department of Pathology, Griffith Medical School and Griffith Health Institute, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Alfred King Yin
authors.initials: AK
authors.lastname: Lam
authors.affiliation: Clinical Division, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Chung Hin
authors.initials: CH
authors.lastname: Chui
authors.affiliation: Sun Yat Sen University, School of Pharmaceutical Sciences, Guangzhou, China.
authors.forename: Albert Sun Chi
authors.initials: AS
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Lam
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Johnny Cheuk On
authors.initials: JC
authors.lastname: Tang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D011804:Quinolines; D012333:RNA, Messenger; C037219:quinoline; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Cell cytotoxicity; Cyclooxygenase 2; Dinoprostone; Esophageal squamous cell carcinoma; Heterografts; Nude-mice; PPAR delta; Quinolines; Real-time polymerase chain reaction; Reverse transcription polymerase chain reaction