Reactivation of methylation-silenced tumor suppressor gene p161NK4a by nordihydroguaiaretic acid and its implication in G1 cell cycle arrest
Reactivation of methylation-silenced tumor suppressor gene p161NK4a by nordihydroguaiaretic acid and its implication in G1 cell cycle arrest
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DOI：
10.1016/j.lfs.2007.11.013
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发表时间：
2008-01-30
期刊：
影响因子：
6.1
通讯作者：
Ma, Xu
中科院分区：
文献类型：
--
作者：
Cui, Yi;Lu, Cailing;Ma, Xu
植物雌激素，包括异黄酮和木酚素两大类，是具有弱雌激素活性的化学物质，天然存在于许多食物和草药中。最近，一些有趣的研究报告称，一些异黄酮可以影响 DNA 甲基化状态。然而，人们对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，我们研究了木酚素家族成员去甲二氢愈创木酸 (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 逆转了 p161NK4a CpG 岛高甲基化，并恢复了其在两种细胞系中的转录和表达。细胞计数分析表明，NDGA 通过将细胞阻滞在 G1 期来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 诱导癌细胞的细胞衰老。这是第一项研究证明木酚素家族的成员可以诱导人类癌细胞系去甲基化，这表明在预防或治疗癌症方面存在一种新的表观遗传机制。 (C) 2007 Elsevier Inc. 保留所有权利。
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.