title: Niclosamide induced cell apoptosis via upregulation of ATF3 and activation of PERK in Hepatocellular carcinoma cells.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of most common and aggressive human malignancies in the world, especially, in eastern Asia, and its mortality is very high at any phase. We want to investigate mechanism of niclosamide inducing cell apoptosis in HCC.
  
  
  METHODS
  Two hepatoma cell lines were used to evaluate activity of niclosamide inducing cell apoptosis and study its mechanism. Quantitative real-time PCR and western blotting were used in analysis of genes expression or protein active regulated by niclosamide.
  
  
  RESULTS
  Niclosamide remarkably induced cell apoptosis in hepatoma cells. Furthermore, our study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to niclosamide. niclosamide also significantly increase activating transcription factor 3 (ATF3), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expression in HCC cells. It's suggested that the function of niclosamide was abrogated by PERK inhibitor or absent ATF3. Expression of PERK and CHOP is correlated with ATF3 level in the cells.
  
  
  CONCLUSIONS
  Taken together, our results indicate that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in HCC cells. In this study, the new mechanism of niclosamide as anti-cancer we investigated, too.
authors.affiliation: Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd, Biology and Pharmacy Building, suite 6-208, Shanghai, 200240, People's Republic of China. wengshunyan@hotmail.com.|The Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, People's Republic of China. wengshunyan@hotmail.com.|School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, People's Republic of China. wengshunyan@hotmail.com.
authors.forename: Shunyan
authors.initials: S
authors.lastname: Weng
authors.affiliation: The Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, People's Republic of China. Abang1212@sjtu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: The Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, People's Republic of China. dengqingemma@sjtu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd, Biology and Pharmacy Building, suite 6-208, Shanghai, 200240, People's Republic of China. Wangjiaxian1993@foxmail.com.
authors.forename: Jiaxian
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, People's Republic of China. Yanyu@sjtu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd, Biology and Pharmacy Building, suite 6-208, Shanghai, 200240, People's Republic of China. JianweiZ@SJTU.EDU.CN.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd, Biology and Pharmacy Building, suite 6-208, Shanghai, 200240, People's Republic of China. yunsheng@sjtu.edu.cn.|The Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai, 200240, People's Republic of China. yunsheng@sjtu.edu.cn.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D051700:Activating Transcription Factor 3 / Q000187:drug effects* / Q000235:genetics; D051701:Activating Transcription Factor 4 / Q000187:drug effects / Q000235:genetics; D000871:Anthelmintics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D055786:Gene Knockout Techniques; D056945:Hep G2 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms; D009534:Niclosamide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D019892:eIF-2 Kinase / Q000187:drug effects* / Q000378:metabolism
chemical_list: C490449:ATF3 protein, human; C497109:ATF4 protein, human; D051700:Activating Transcription Factor 3; D000871:Anthelmintics; C497249:DDIT3 protein, human; D012333:RNA, Messenger; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D009534:Niclosamide; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase