title: Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells.
abstract: OBJECTIVE
  To investigate the anti-cancer mechanisms of Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) using a human colon cancer cell line (COLO).
  
  
  METHODS
  Cytotoxic effects of VCA on COLO cells were determined by 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay in vitro and tumor-killing effects in vivo. To study the mechanisms involved, the expression of various pro-caspases, anti-apoptotic proteins, and death receptors was determined by western blot. To determine which death receptor is involved in VCA-induced apoptosis of COLO cells, cytotoxicity was examined by MTT assay after treatment with agonists or antagonists of death receptors.
  
  
  RESULTS
  VCA killed COLO cells in a time- and dose-dependent manner and induced complete regression of tumors in nude mice transplanted with COLO cells. Treatment of COLO cells with VCA activated caspase-2, -3, -8, and -9 and decreased expression of anti-apoptotic molecules including receptor interacting protein, nuclear factor-kappaB, X-linked inhibitor of apoptosis protein, and Akt/protein kinase B. We then examined the involvement of death receptors in VCA-induced apoptosis. Only tumor necrosis factor receptor 1, among the death receptors examined, was involved in apoptosis of COLO cells, evidenced by inhibition of VCA-induced apoptosis and decreased activation of caspases, particularly caspase-8, by tumor necrosis factor receptor 1 antagonizing antibody.
  
  
  CONCLUSIONS
  VCA-induced apoptotic COLO cell death is due to the activation of caspases and inhibition of anti-apoptotic proteins, in part through the tumor necrosis factor receptor 1 signaling pathway.
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Lee-Yong
authors.initials: LY
authors.lastname: Khil
authors.forename: Wi
authors.initials: W
authors.lastname: Kim
authors.forename: Suyun
authors.initials: S
authors.lastname: Lyu
authors.forename: Won-Bong
authors.initials: WB
authors.lastname: Park
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Yoon
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology; D020169:Caspases / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D028321:Plant Preparations / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000502:physiology; D054790:Ribosome Inactivating Proteins, Type 2; D015398:Signal Transduction / Q000502:physiology; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014118:Toxins, Biological / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D047990:TNF Receptor-Associated Factor 1; D014118:Toxins, Biological; C488862:mistletoe lectin I; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases