title: β-Elemene Inhibits Cell Proliferation by Regulating the Expression and Activity of Topoisomerases I and IIα in Human Hepatocarcinoma HepG-2 Cells.
abstract: OBJECTIVE
  To investigate the effects of β-Elemene (β-ELE) on the proliferation, apoptosis, and topoisomerase I (TOPO I) and topoisomerase IIα (TOPO IIα) expression and activity of human hepatocarcinoma HepG-2 cells.
  
  
  METHODS
  After treatment with β-ELE, morphological alterations of HepG-2 cells were observed under an inverted microscope. Cell proliferation was assessed using an MTT assay, cell cycles were analyzed using flow cytometry, and apoptosis was detected by Annexin V/PI staining. The expression of TOPO I and TOPO IIα was analyzed by Western blot techniques, and their activity was measured using the TOPO I-mediated, supercoiled pBR322 DNA relaxation and TOPO IIα-mediated Kinetoplast DNA (kDNA) decatenation assays, respectively. Supercoiled pBR322 and kDNA were also used to determine the direct effect of β-ELE on DNA breaks.
  
  
  RESULTS
  β-ELE significantly inhibited HepG-2 cell proliferation in a dose- and time-dependent manner. β-ELE also induced tumor cell arrest at S phase, induced cell apoptosis, and downregulated the protein expression of TOPO I and TOPO IIα in a dose-dependent manner. β-ELE also inhibited TOPO I- and TOPO IIα-mediated DNA relaxation but did not directly induce DNA breakage at any concentration.
  
  
  CONCLUSIONS
  β-ELE could inhibit the proliferation of HepG-2 cells and interfere with the expression and activity of TOPO I and TOPO IIα.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gong
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Ya-jie
authors.initials: YJ
authors.lastname: Gao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Ping-ping
authors.initials: PP
authors.lastname: Zhai
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Basic Medicine, Dalian Medical University, Dalian, Liaoning 116023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
authors.forename: Xiao-nan
authors.initials: XN
authors.lastname: Cui
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis* / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage*
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D012717:Sesquiterpenes; C445979:beta-elemene; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II