Article Text

  1. D M Aresvik1,
  2. R D Pettersen1,
  3. T G Abrahamsen2,3,
  4. M S Wright1
  1. 1Department of Paediatric Research, Division of Paediatrics, Rikshospitalet University Hospital, Oslo, Norway
  2. 2Division of Paediatrics, Rikshospitalet University Hospital, Oslo, Norway
  3. 3University of Oslo, Oslo, Norway


Objective Cytostatics are widely used to treat paediatric cancer with the intention to eliminate cancer cells by apoptosis. 5-Fluorouracil (5-FU) is frequently used in the treatment of malignancies. Previous studies with 5-FU and different cell lines indicate that the pro-apoptotic protein Bax and the tumour suppressor protein p53 are central actors in this process. The acute leukaemic T-cell line Jurkat E6 has mutations in both genes and 5-FU therefore needs to activate alternative death pathways. Previously, we have shown that incubation with 5-FU apparently triggers apoptosis in Jurkat cells in a dose-dependent manner, with a maximal response within 72 h; death response was attenuated in the presence of general caspase inhibitor.

Methods Jurkat T cells were treated with 5-FU for different time periods. Caspase-3 activity and changes in the mitochondrial membrane potential were measured by flow cytometry. Expression of various proteins, eg, PARP, NOXA and Mcl-1, was examined by Western blot.

Results Flow cytometric analysis showed activation of caspase-3 in a time and dose-dependent manner. Using Western blot we observed decreasing levels of anti-apoptotic and increasing levels of pro-apoptotic proteins. Treatment with 5-FU induced a breakdown of the mitochondrial membrane potential.

Conclusion Our results indicate that Jurkat T cells, previously thought to be resistant, can indeed be induced to undergo cell death, using sufficient doses of 5-FU and incubation time. The apoptotic pathway induced by 5-FU in this cell line may provide a rational basis for the design of chemotherapy.

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