title: Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.
abstract: OBJECTIVE
  In the current study the antiproliferative effect of arctigenin, plant lignin, was evaluated on human colon cancer cell line HT-29. Furthermore, attempts were made to explore the signaling mechanism which may be responsible for its effect.
  
  
  METHODS
  Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line.
  
  
  RESULTS
  MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure.
  
  
  CONCLUSIONS
  Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.
authors.forename: Qing-chun
authors.initials: QC
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Liang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Guang-rui
authors.initials: GR
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D005663:Furans; D017705:Lignans; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; C071942:arctigenin