title: Molecular mechanisms of denbinobin-induced anti-tumorigenesis effect in colon cancer cells.
abstract: OBJECTIVE
  To explore both the in vitro and in vivo effects of denbinobin against colon cancer cells and clarify its underlying signal pathways.
  
  
  METHODS
  We used COLO 205 cancer cell lines and nude mice xenograft model to study the in vitro and in vivo anti-cancer effects of denbinobin.
  
  
  RESULTS
  Denbinobin at concentration of 10-20 micromol/L dose-dependently suppressed COLO 205 cell proliferation by MTT test. Flow cytometry analysis and DNA fragmentation assay revealed that 10-20 micromol/L denbinobin treatment induced COLO 205 cells apoptosis. Western blot analysis showed that caspases 3, 8, 9 and Bid protein were activated by denbinobin treatment to COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation. Pretreatment of MEK 1 inhibitor (U10126), but not p38 inhibitor (SB203580) and JNK inhibitor (SP600125), reversed denbinobin-induced caspase 8, 9 and Bid activation in COLO 205 cells suggesting that extracellular signal-regulated kinase were involved in the denbinobin-induced apoptosis in COLO 205 cells. Significant regression of tumor up to 68% was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with denbinobin 50 mg/kg intraperitoneally.
  
  
  CONCLUSIONS
  Our findings suggest that denbinobin could inhibit colon cancer growth both in vitro and in vivo. Activation of extrinsic and intrinsic apoptotic pathways and AIF were involved in the denbinobin-induced COLO 205 cell apoptosis.
authors.affiliation: Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, China.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Yang
authors.forename: Yih-Huei
authors.initials: YH
authors.lastname: Uen
authors.forename: Fat-Moon
authors.initials: FM
authors.lastname: Suk
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Liang
authors.forename: Ying-Jan
authors.initials: YJ
authors.lastname: Wang
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Li
authors.forename: Shyr-Yi
authors.initials: SY
authors.lastname: Lin
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010616:Phenanthrenes / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D010616:Phenanthrenes; C436544:denbinobin