title: Anti-cancer Activity of Osmanthus matsumuranus Extract by Inducing G2/M Arrest and Apoptosis in Human Hepatocellular Carcinoma Hep G2 Cells.
abstract: BACKGROUND
  Osmanthus matsumuranus, a species of Oleaceae, is found in East Asia and Southeast Asia. The bioactivities of O. matsumuranus have not yet been fully understood. Here, we studied on the molecular mechanisms underlying anti-cancer effect of ethanol extract of O. matsumuranus (EEOM).
  
  
  METHODS
  Inhibitory effect of EEOM on cell growth and proliferation was determined by WST assay in various cancer cells. To investigate the mechanisms of EEOM-mediated cytotoxicity, HepG2 cells were treated with various concentration of EEOM and analyzed the cell cycle arrest and apoptosis induction by flow cytometry, Western blot analysis, 4,6-diamidino-2-phenylindole (DAPI) staining and DNA fragmentation.
  
  
  RESULTS
  EEOM showed the cytotoxic activities in a dose-dependent manner in various cancer cell lines but not in normal cells, and HepG2 cells were most susceptible to EEOM-induced cytotoxicity. EEOM induced G2/M arrest in HepG2 cells associated with decreased expression of cyclin-dependent kinase 1 (CDK1), cyclin A and cylcin B, and increased expression of phospho-checkpoint kinase 2, p53 and CDK inhibitor p21. Immunofluorescence staining showed that EEOM-treated HepG2 increased doublet nuclei and condensed actin, resulting in cell rounding. Furthermore, EEOM-mediated apoptosis was determined by Annexin V staining, chromatin condensation and DNA fragmentation. EEOM caused upregulation of FAS and Bax, activation of caspase-3, -8, -9, and fragmentation of poly ADP ribose polymerase.
  
  
  CONCLUSIONS
  These results suggest that EEOM efficiently inhibits proliferation of HepG2 cells by inducing both G2/M arrest and apoptosis via intrinsic and extrinsic pathways, and EEOM may be used as a cancer chemopreventive agent in the food or nutraceutical industry.
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busan, Korea; Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busan, Korea.
authors.forename: Soojung
authors.initials: S
authors.lastname: Jin
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busan, Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busan, Korea.
authors.forename: You Na
authors.initials: YN
authors.lastname: Oh
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busan, Korea; Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busan, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busan, Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busan, Korea; Department of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan, Korea; Anti-Aging Research Center, Dong-Eui University, Busan, Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busan, Korea; Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busan, Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
keywords: Anticancer effect; Apoptosis; Cell cycle arrest; Hep G2 cells; Osmanthus matsumuranus