The irinotecan/5-fluorouracil combination induces apoptosis and enhances manganese superoxide dismutase activity in HT-29 human colon carcinoma cells.
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.
Grivicich
Ivana
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
Andréa
A
da Rocha
Adriana B
AB
Kayser
Guilherme B
GB
Schunemann
Daniel P
DP
Grass
Luciano B
LB
Alves
Pedro A G
PA
Henriques
João A P
JA
Schwartsmann
Gilberto
G
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*
D000970:Antineoplastic Agents; D000077146:Irinotecan; D013482:Superoxide Dismutase; D005472:Fluorouracil; D002166:Camptothecin