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姜黄素作为表观遗传事件的调节剂。

Curcumin as a regulator of epigenetic events.

机构信息

Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg.

出版信息

Mol Nutr Food Res. 2013 Sep;57(9):1619-29. doi: 10.1002/mnfr.201300201. Epub 2013 Jun 11.

Abstract

Epigenetic alterations correspond to changes in DNA methylation, covalent modifications of histones, or altered miRNA expression patterns. These three mechanisms are interconnected and appear to be key players in tumor progression and failure of conventional chemotherapy. Dietary components emerged as a promising source of new epigenetically active compounds able to reverse these alterations and to actively regulate gene expression as well as molecular targets implicated in tumorigenesis. The polyphenolic compound curcumin (diferuloylmethane), a yellow spice that enters into the composition of curry, already described for its diverse and broad biological activities, is nowadays well described as an inhibitor of DNA methyltransferase so that it is considered as a DNA hypomethylating agent. It reestablishes the balance between histone acetyl transferase and histone deacetylase (HDAC 1, 3, 4, 5, 8) activity to selectively activate or inactivate the expression of genes implicated in cancer death and progression, respectively. Finally curcumin modulates miRNAs (miR-15a, miR-16, miR-21, miR-22, miR-26, miR-101, miR-146, miR-200, miR-203, and let-7) and their multiple target genes. In conclusion, this dietary compound is able to restore the epigenetic regulation balance and appears as an attractive preventive and/or therapeutic approach against human cancer.

摘要

表观遗传改变对应于 DNA 甲基化、组蛋白的共价修饰或 miRNA 表达模式的改变。这三种机制相互关联,似乎是肿瘤进展和传统化疗失败的关键因素。膳食成分作为一种有前途的新的表观遗传活性化合物来源,能够逆转这些改变,并积极调节基因表达以及肿瘤发生中涉及的分子靶点。多酚化合物姜黄素(二芳基甲甲烷),一种黄色香料,进入咖喱的成分,已经因其多样和广泛的生物学活性而被描述,现在被很好地描述为 DNA 甲基转移酶抑制剂,因此被认为是一种 DNA 去甲基化剂。它重新建立组蛋白乙酰转移酶和组蛋白去乙酰化酶(HDAC1、3、4、5、8)活性之间的平衡,分别选择性地激活或失活与癌症死亡和进展相关的基因的表达。最后,姜黄素调节 miRNA(miR-15a、miR-16、miR-21、miR-22、miR-26、miR-101、miR-146、miR-200、miR-203 和 let-7)及其多个靶基因。总之,这种膳食化合物能够恢复表观遗传调控的平衡,作为一种有吸引力的预防和/或治疗人类癌症的方法。

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