National Center for Natural Products Research, University of Mississippi, University, Mississippi 38677, United States.
Chem Res Toxicol. 2012 Jan 13;25(1):61-73. doi: 10.1021/tx200378c. Epub 2011 Oct 28.
Aberrant epigenetic alterations in the genome such as DNA methylation and chromatin remodeling play a significant role in breast cancer development. Since epigenetic alterations are considered to be more easily reversible compared to genetic changes, epigenetic therapy is potentially very useful in reversing some of these defects. Methylation of CpG islands is an important component of the epigenetic code, and a number of genes become abnormally methylated in breast cancer patients. Currently, several epigenetic-based synthetic drugs that can reduce DNA hypermethylation and histone deacetylation are undergoing preclinical and clinical trials. However, these chemicals are generally very toxic and do not have gene specificity. Epidemiological studies have shown that Asian women are less prone to breast cancer due to their high consumption of soy food than the Caucasian women of western countries. Moreover, complementary/and or alternative medicines are commonly used by Asian populations which are rich in bioactive ingredients known to be chemopreventive against tumorigenesis in general. Examples of such agents include dietary polyphenols, (-)-epigallocatechin-3-gallate (EGCG) from green tea, genistein from soybean, isothiocyanates from plant foods, curcumin from turmeric, resveratrol from grapes, and sulforaphane from cruciferous vegetables. These bioactive components are able to modulate epigenetic events, and their epigenetic targets are known to be associated with breast cancer prevention and therapy. This approach could facilitate the discovery and development of novel drugs for the treatment of breast cancer. In this brief review, we will summarize the epigenetic events associated with breast cancer and the potential of some of these bioactive dietary components to modulate these events and thus afford new therapeutic or preventive approaches.
基因组中的异常表观遗传改变，如 DNA 甲基化和染色质重塑，在乳腺癌的发生发展中起着重要作用。由于与遗传改变相比，表观遗传改变更容易逆转，因此表观遗传疗法在逆转其中一些缺陷方面具有很大的潜力。CpG 岛的甲基化是表观遗传密码的一个重要组成部分，许多基因在乳腺癌患者中出现异常甲基化。目前，有几种基于表观遗传学的合成药物可以减少 DNA 过度甲基化和组蛋白去乙酰化，正在进行临床前和临床试验。然而，这些化学物质通常毒性很大，并且没有基因特异性。流行病学研究表明，亚洲女性由于大量食用豆制品，患乳腺癌的风险比西方国家的白种女性低。此外，亚洲人群普遍使用补充/替代医学，这些医学富含具有抗肿瘤作用的生物活性成分。这类药物的例子包括膳食多酚、绿茶中的 (-)-表没食子儿茶素-3-没食子酸酯（EGCG）、大豆中的染料木黄酮、植物性食物中的异硫氰酸酯、姜黄中的姜黄素、葡萄中的白藜芦醇和十字花科蔬菜中的萝卜硫素。这些生物活性成分能够调节表观遗传事件，其表观遗传靶标与乳腺癌的预防和治疗有关。这种方法可以促进新型乳腺癌治疗药物的发现和开发。在这篇简短的综述中，我们将总结与乳腺癌相关的表观遗传事件，以及其中一些生物活性膳食成分调节这些事件的潜力，从而提供新的治疗或预防方法。
