Dietary polyphenols may affect DNA methylation
Dietary polyphenols may affect DNA methylation
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DOI：
10.1093/jn/137.1.223s
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Yang, Chung S.
中科院分区：
文献类型：
--
作者：
Fang, Mingzhu;Chen, Dapeng;Yang, Chung S.
某些膳食多酚，例如绿茶中的 (-)-表没食子儿茶素 3-没食子酸酯 (EGCG) 和大豆中的染料木黄酮，已被证明可以在体外抑制 DNA 甲基转移酶 (DNMT)。这种抑制活性与启动子中 CpG 岛的去甲基化和甲基化沉默基因的重新激活有关，例如 P16(INK4a)、视黄酸受体 β、O-6-甲基鸟嘌呤甲基转移酶、人 mutL 同源物 1 和谷胱甘肽 S-转移酶-pi。这些活性已在人类食管癌、结肠癌、前列腺癌和乳腺癌细胞系中观察到，并且通过组蛋白脱乙酰酶抑制剂的存在或长期治疗可以增强该活性。许多其他多酚化合物抑制 DNMT 的活性较低。儿茶酚多酚可能通过 S-腺苷-L-蛋氨酸甲基化产生 S-腺苷-L-高半胱氨酸来间接抑制 DNMT。理论上，通过DNMT抑制剂预防或逆转高甲基化引起的关键肿瘤抑制基因或受体基因失活可能是预防癌症的有效方法。由于大多数多酚化合物的生物利用度相当低，膳食多酚对人类DNA甲基化的影响有多大尚不清楚。正常饮食中摄入单一多酚化合物的影响可能微不足道。然而，多酚与膳食组蛋白脱乙酰酶抑制剂的组合以及不同膳食化学物质的相加作用可能会产生一些效果。另一方面，膳食补充剂中摄入过量的多酚可能会影响 DNA 甲基化状态。所有这些可能性都有待检验。
Certain dietary polyphenols, such as (-)-epigallocatechin 3-gallate (EGCG) from green tea and genistein from soybean, have been demonstrated to inhibit DNA methyltransferases (DNMT) in vitro. This inhibitory activity is associated with the demethylation of the CpG islands in the promoters and the reactivation of methylation-silenced genes such as P16(INK4a), retinoic acid receptor beta, O-6-methylguanine methyltransferase, human mutL homolog 1, and glutathione S-transferase-pi. These activities have been observed in human esophageal, colon, prostate, and mammary cancer cell lines, and the activity can be enhanced by the presence of histone deacetylase inhibitors or by a longer-term treatment. Many other polyphenolic compounds have lower activities in inhibiting DNMT. Catechol polyphenols may indirectly inhibit DNMT by generating S-adenosyl-L-homocysteine on their methylation by S-adenosyl-L-methionine. In theory, prevention or reversal of hypermethylation-induced inactivation of key tumor suppression genes or receptor genes by DNMT inhibitors could be an effective approach for cancer prevention, Because of the rather low bioavailability of most polyphenolic compounds, how much of an effect dietary polyphenols would have on DNA methylation in humans is not clear. The effect of normal dietary consumption of a single polyphenolic compound is probably insignificant. However, the combination of polyphenols with dietary histone deacetylase inhibitors and the additive effect of different dietary chemicals may produce some effects. On the other hand, the consumption of excessive amounts of polyphenols in dietary supplements may affect DNA methylation status. All these possibilities remain to be examined.