Instituto de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, Barcelona, Spain.
Biochem Pharmacol. 2012 Nov 1;84(9):1133-42. doi: 10.1016/j.bcp.2012.08.003. Epub 2012 Aug 14.
The effects of mithramycin SK (MSK) and demycarosyl-3D-β-D-digitoxosyl-mithramycin SK (DIG-MSK; EC-8042), two novel analogs of the antitumor antibiotic mithramycin A, on gene transcription were examined in human HCT116 colon carcinoma cells by quantitative real-time PCR of 89 genes mainly involved in cell cycle control. Each one of the analogs down-regulated a different set of genes, while only five genes were down-regulated by both compounds. Moreover, other genes were significantly up-regulated, among them p21(WAF1)/CDKN1A which is involved in halting cells at the G1 and G2/M checkpoints. These results are rationalized in terms of MSK or DIG-MSK competition with various transcription factors for binding to consensus C/G-rich tracts encompassed in gene promoters. Changes in cell cycle distribution and protein levels after treatment with every analog were consistent with changes observed in gene expression.
米托霉素 SK（MSK）和去甲卡波霉素-3D-β-D-地高辛基米托霉素 SK（DIG-MSK；EC-8042）是抗肿瘤抗生素米托霉素 A 的两种新型类似物，我们通过定量实时 PCR 检测了这两种类似物对主要涉及细胞周期控制的 89 个基因的转录的影响，这些基因均在人 HCT116 结肠癌细胞中。这两种类似物均下调了不同的基因集，而只有 5 个基因被这两种化合物共同下调。此外，还有许多基因显著上调，其中包括参与阻止细胞在 G1 和 G2/M 检验点的 p21（WAF1）/CDKN1A。这些结果可以用 MSK 或 DIG-MSK 与各种转录因子竞争结合基因启动子中包含的各种 C/G 富集区来合理化。每个类似物处理后细胞周期分布和蛋白水平的变化与基因表达观察到的变化一致。
