title: Induction of cell cycle arrest and apoptosis by 5-fluorouracil in laryngeal cancer cells containing HPV16 E6 and E7 oncoproteins.
abstract: OBJECTIVE
  To investigate the cytotoxic effect of 5-fluorouracil (5Fu) on HPV16-associated laryngeal cancer cells.
  
  
  METHODS
  Cytotoxicity assay and TUNEL assay were used to assess the effect of 5Fu on laryngeal cancer cells transfected with HPV16 E6 or E7.
  
  
  RESULTS
  5Fu induced apoptosis in the cells either with or without HPV16 in a dose- and time-dependent manner. 5Fu caused the accumulation of active pRb and p21(WAF1/CIP1), together with an increase in Bak and Bax expression and a decrease in Bcl-2 levels in all the transfected cells. G(1)/S phase cell cycle arrest was associated with the antiproliferation activity of 5Fu. 5Fu also presented some effects on the E6 and E7 oncoproteins.
  
  
  CONCLUSIONS
  HPV16 E6 and E7 oncoproteins do not prevent 5Fu-medicated apoptosis and G(1)/S cell arrest in laryngeal cancers. The sensitivity of 5Fu treatment is associated with the decrease of Bcl-2 and/or the increase in Bak and p21(WAFI/CIP1).
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Han Ching
authors.initials: HC
authors.lastname: Liu
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Vlantis
authors.forename: Michael C F
authors.initials: MC
authors.lastname: Tong
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Chan
authors.forename: C Andrew
authors.initials: CA
authors.lastname: van Hasselt
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015513:Oncogene Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D014162:Transfection; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; C068651:E6 protein, Human papillomavirus type 16; D015513:Oncogene Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D050998:bcl-2 Homologous Antagonist-Killer Protein; C059731:oncogene protein E7, Human papillomavirus type 16; D005472:Fluorouracil