Current Medicinal Chemistry, 2010, 17(20):2141-51.

Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components

Yuanyuan Li, and Trygve O. Tollefsbol

Department of Biology, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA; et al

It is well established that aberrant gene regulation by epigenetic mechanisms can develop as a result of pathological processes such as cancer. Methylation of CpG islands is an important component of the epigenetic code and a number of genes become abnormally methylated during tumorigenesis. Some bioactive food components have been shown to have cancer inhibition activities by reducing DNA hypermethylation of key cancer-causing genes through their DNA methyltransferase (DNMT) inhibition properties. The dietary polyphenols, (-)-epigallocatechin- 3-gallate (EGCG) from green tea, genistein from soybean and possibly isothiocyanates from plant foods, are some examples of these bioactive food components modulated by epigenetic factors. The activity of cancer inhibition generated from dietary polyphenols is associated with gene reactivation through demethylation in the promoters of methylation-silenced genes such as p16INK4a and retinoic acid receptor beta. The effects of dietary polyphenols such as EGCG on DNMTs appear to have their direct inhibition by interaction with the catalytic site of the DNMT1 molecule, and may also influence methylation status indirectly through metabolic effects associated with energy metabolism. Therefore, reversal of hypermethylation-induced inactivation of key tumor suppression genes by dietary DNMT inhibitors could be an effective approach to cancer prevention and therapy. In this analysis, we focus on advances in understanding the effects of dietary polyphenols on DNA methylation modulation during the process of cancer development, which will offer exciting new opportunities to explore the role of diet in influencing the biology of cancer and to understand the susceptibility of the human epigenome to dietary effects.

荷兰《现代医药化学》，2010年

膳食成分的生物活性使DNA 甲基化对癌症预防和治疗的影响

李园园和特里格弗 O 泰勒福伯

美国阿拉巴马大学伯明翰分校生物学院等

总所周知，表观遗传机制的异常基因调控会导致例如癌症等病理过程。CpG 岛的甲基化是表观遗传编码的重要组成部分，并且在在肿瘤发生过程中部分基因变得异常甲基化。一些具生物活性的食品成分已被证明通过其 DNA 甲基转移酶 (DNMT) 缓蚀性能来减少关键致癌基因DNA 的甲基化可以抑制癌症活性。日常的饮食多酚、从绿茶提取的（-）-表儿茶素-3-没食子酸酯 (EGCG)、从大豆提取的染料木素和可能来自植物性食品的异硫氰酸酯，是表观遗传因素调节具生物活性食品成分的一些例子。饮食多酚生成的抑制癌症的活性与通过去甲基化启动子中的甲基化沉默基因，比如 p16INK4a 和视黄酸受体 β导致的基因激活有关。膳食多酚如EGCG对DNMTs的影响似乎通过与DNMT1分子催化位点的相互作用有直接的抑制作用，也可能会间接通过代谢作用与能量代谢影响甲基化状态。因此，通过膳食DNMT抑制剂逆转关键肿瘤抑制基因的高甲基化诱导失活可能是预防和治疗癌症的有效途径。在此分析中，我们专注于了解饮食多酚在癌症发展过程中对DNA 甲基化调节的影响，将提供令人兴奋的新机会，来探讨饮食在影响癌症生物学方面的作用，了解人类表观基因组对膳食作用的易感性。