title: Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice.
abstract: Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer.
  
  
  
  The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin.
  
  
  
  The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53.
  
  
  
  The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.
authors.affiliation: 1 Chongqing Key Laboratory of Hepatobiliary Surgery, Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.|2 Division of Basic Medical Science, Chongqing Three Gorges Medical College, Chongqing, Wanzhou, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Huang
authors.affiliation: 2 Division of Basic Medical Science, Chongqing Three Gorges Medical College, Chongqing, Wanzhou, People's Republic of China.|3 Department of Histology and Embryology, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Runqin
authors.initials: R
authors.lastname: Li
authors.affiliation: 4 Department of Hepatobiliary Surgery, The Third Hospital of Mianyang, Mianyang, Sichuan, People's Republic of China.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1 Chongqing Key Laboratory of Hepatobiliary Surgery, Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Gong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D039823:Iridoids / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D039823:Iridoids; D016159:Tumor Suppressor Protein p53; C102609:amarogentin; C509186:TERT protein, human; D019098:Telomerase
keywords: amarogentin; hepatocellular carcinoma; human telomerase reverse transcriptase; p53