title: The irinotecan/5-fluorouracil combination induces apoptosis and enhances manganese superoxide dismutase activity in HT-29 human colon carcinoma cells.
abstract: BACKGROUND
  We examined whether induction of apoptosis and Mn-superoxide dismutase (Mn-SOD) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activities were involved in the greater cytotoxicity of the irinotecan (CPT-11)/5-fluorouracil (5-FU) combination for human colon cancer cells when compared to both drugs alone.
  
  
  METHODS
  HT-29 and SNU-C4 human colon carcinoma cell lines were treated with 5-FU and CPT-11, then apoptosis was evaluated by flow cytometry and SOD activities were determined by polyacrylamide gel electrophoresis.
  
  
  RESULTS
  Enhanced apoptosis of HT-29 cells was observed with all treatments containing 5-FU in SNU-C4 cells; however, in HT-29 cells, apoptosis was enhanced only with the CPT-11/5-FU combination. In the SNU-C4 cell line, none of the treatments exerted a significant effect on Cu,Zn-SOD or Mn-SOD activity. However, in HT-29 cells, the CPT-11/5-FU combination enhanced Mn-SOD activity when compared to cells treated with CPT-11 alone. Nevertheless, the combined treatment did not interfere with Cu,Zn-SOD activity.
  
  
  CONCLUSIONS
  Treatment with the CPT-11/5-FU combination may promote in HT-29 cell apoptosis by enhancing Mn-SOD activity.
authors.affiliation: South-American Office of Anticancer Drug Development, Porto Alegre, Centro de Pesquisas em Ciências Médicas, Universidade Luterana do Brasil, Canoas, Brazil. grivicich@terra.com.br
authors.forename: Ivana
authors.initials: I
authors.lastname: Grivicich
authors.forename: Andréa
authors.initials: A
authors.lastname: Regner
authors.forename: Adriana B
authors.initials: AB
authors.lastname: da Rocha
authors.forename: Guilherme B
authors.initials: GB
authors.lastname: Kayser
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Schunemann
authors.forename: Luciano B
authors.initials: LB
authors.lastname: Grass
authors.forename: Pedro A G
authors.initials: PA
authors.lastname: Alves
authors.forename: João A P
authors.initials: JA
authors.lastname: Henriques
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003110:Colonic Neoplasms; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D013482:Superoxide Dismutase / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D013482:Superoxide Dismutase; D005472:Fluorouracil; D002166:Camptothecin