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[摘要]：5-Fluorouracil (5-FU) is frequently used in cancer treatment. Previous studies with 5-FU suggest that proapoptotic protein BAX and tumor suppressor protein TP53 are central factors in this process. As the leukemic T cell line Jurkat E6 has mutations in both these genes, we investigated a possible activation of alternative death pathways following 5-FU treatment. Here we show that 5-FU triggers apoptosis in Jurkat cells in a dose-dependent manner. Death responses were only moderately attenuated in the presence of a general caspase inhibitor. However, flow cytometric analysis showed activation of caspase 3 and a slight increase in ROS generation in a time- and dose-dependent manner. Furthermore, we observed 5-FU induced PARP cleavage and notably, reduced expression of antiapoptotic MCL-IL associated with the appearance of proapoptotic MCL-IS. Our results demonstrate the activation of alternative death pathways following treatment with 5-FU, despite mutations in the TP53 and BAX genes. |
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