The irinotecan/5-fluorouracil combination induces apoptosis and enhances manganese superoxide dismutase activity in HT-29 human colon carcinoma cells.

Autor: Grivicich I; 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, Regner A, da Rocha AB, Kayser GB, Schunemann DP, Grass LB, Alves PA, Henriques JA, Schwartsmann G
Jazyk: angličtina
Zdroj: Chemotherapy [Chemotherapy] 2005 May; Vol. 51 (2-3), pp. 93-102. Date of Electronic Publication: 2005 May 09.
DOI: 10.1159/000085617
Abstrakt: 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.
Conclusion: Treatment with the CPT-11/5-FU combination may promote in HT-29 cell apoptosis by enhancing Mn-SOD activity.
(Copyright 2005 S. Karger AG, Basel)
Databáze: MEDLINE