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首页> 外文期刊>Life sciences >Reactivation of methylation-silenced tumor suppressor gene p161NK4a by nordihydroguaiaretic acid and its implication in G1 cell cycle arrest
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Reactivation of methylation-silenced tumor suppressor gene p161NK4a by nordihydroguaiaretic acid and its implication in G1 cell cycle arrest

机译：去甲二氢愈创木酸对甲基化沉默的抑癌基因p161NK4a的激活及其对G1细胞周期阻滞的影响

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Phytoestrogens, including the two major groups isoflavones and lignans, are chemicals with weak estrogenic activity which occur naturally in many foods and herbs. Recently, several intriguing studies reported that some isoflavones can affect DNA methylation status. However, little is known about the effect of plant lignans on epigenetic modification. Using cultured T47D and RKO human cancer cells as a model, we studied the modulating effects of nordihydroguaiaretic acid (NDGA), a member of the lignan family, on the methylation status of the gene promoter region. Our results indicated that NDGA reverses p161NK4a CpG island hypermethylation, and restores its transcription and expression in both cell lines. Cytomettic analysis showed that NDGA significantly affects cell cycle progression by arresting cells at the G1 phase. Consistent with the reacquisition of p161NK4a expression, we also found that NDGA induces cellular senescence in cancer cells. This is the first study demonstrating that a member of the lignan family can induce demethylation in human cancer cell lines, suggesting a novel epigenetic mechanism in the prevention or treatment of cancer. (C) 2007 Elsevier Inc. All rights reserved.
机译：植物雌激素，包括异黄酮和木脂素两大类，是雌激素活性弱的化学物质，许多食物和草药中都天然存在。最近，一些有趣的研究报告说一些异黄酮会影响DNA甲基化状态。然而，关于植物木脂素对表观遗传修饰的影响知之甚少。使用培养的T47D和RKO人类癌细胞作为模型，我们研究了木脂素家族成员去氢二氢愈创木酸（NDGA）对基因启动子区域甲基化状态的调节作用。我们的结果表明，NDGA可逆转p161NK4a CpG岛的超甲基化，并在两种细胞系中恢复其转录和表达。细胞计数分析表明，NDGA通过将细胞停滞在G1期而显着影响细胞周期进程。与p161NK4a表达的重新获得一致，我们还发现NDGA诱导癌细胞中的细胞衰老。这是第一个证明木脂素家族成员可以诱导人癌细胞系中去甲基化的研究，这表明了预防或治疗癌症的新表观遗传机制。 （C）2007 Elsevier Inc.保留所有权利。

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