Mansilla Sylvia, Portugal José
Instituto de Biologia Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Josep Samitier 1-5, E-08028 Barcelona, Spain.
Biochimie. 2008 Jul;90(7):976-87. doi: 10.1016/j.biochi.2007.12.008. Epub 2008 Jan 5.
The analysis of how anthracyclines interfere with DNA-protein complexes, and the evaluation of their effects on gene transcription, can promote the development of new more specific anti-tumour agents. Daunorubicin and the bisintercalating anthracycline WP631 (which binds more tightly to DNA) have been compared for their ability to inhibit Sp1-DNA interactions and gene transcription. WP631 is more efficient at inhibiting transcription initiation from promoters containing an Sp1-binding site, and it is a potent inhibitor of Sp1-activated transcription both in vitro and in human cell lines. The analysis of gene expression profiles using arrays, which include several genes containing Sp1-putative binding sites, suggests that changes in the transcriptome induce cell cycle arrest and drive a time-dependent response of cells to death stimuli through distinct pathways, which rely on the anthracycline used and its concentration.
对蒽环类药物如何干扰DNA-蛋白质复合物以及评估它们对基因转录的影响进行分析，可促进新型更具特异性抗肿瘤药物的研发。已比较柔红霉素和双嵌入型蒽环类药物WP631（其与DNA结合更紧密）抑制Sp1-DNA相互作用和基因转录的能力。WP631在抑制来自含有Sp1结合位点的启动子的转录起始方面更有效，并且在体外和人细胞系中都是Sp1激活转录的有效抑制剂。使用包含几个含有Sp1假定结合位点的基因的阵列对基因表达谱进行分析表明，转录组的变化会诱导细胞周期停滞，并通过不同途径驱动细胞对死亡刺激的时间依赖性反应，这些途径取决于所使用的蒽环类药物及其浓度。
