Mansilla Sylvia, Priebe Waldemar, Portugal José
Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Josep Samitier, 1-5, E-08028 Barcelona, Spain.
Eur J Pharmacol. 2006 Jul 1;540(1-3):34-45. doi: 10.1016/j.ejphar.2006.04.035. Epub 2006 Apr 30.
Exposure of Jurkat T lymphocytes containing functional p53 to nanomolar concentrations of bisanthracycline WP631 resulted in arrest at the G2/M checkpoint and transient senescence-like phenotype in the presence of DNA synthesis. The cells entered crisis, became polyploid, showed aberrant mitotic figures, and died through mitotic catastrophe. Cell death was accompanied by changes in the expression profile of various oncogenes and tumour suppressor genes including the down-regulation of p53. The changed expression was confirmed for some of these genes using semi-quantitative RT-PCR, and the decline in p53 protein levels was established. Our results suggest that WP631 induced changes in cell cycle control pathways leading to death of Jurkat T cells through mitotic catastrophe, which occurred in the absence of caspase-2 and caspase-3 activities, rather than apoptosis.
含有功能性p53的Jurkat T淋巴细胞暴露于纳摩尔浓度的双蒽环类药物WP631下，在DNA合成存在的情况下会导致细胞在G2/M期检查点停滞，并出现短暂的衰老样表型。细胞进入危机状态，变成多倍体，出现异常有丝分裂图像，并通过有丝分裂灾难死亡。细胞死亡伴随着各种癌基因和肿瘤抑制基因表达谱的变化，包括p53的下调。使用半定量RT-PCR对其中一些基因的表达变化进行了确认，并确定了p53蛋白水平的下降。我们的结果表明，WP631诱导细胞周期控制途径发生变化，导致Jurkat T细胞通过有丝分裂灾难死亡，这一过程发生在缺乏caspase-2和caspase-3活性的情况下，而非凋亡。
