Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia.
Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia.
Biomolecules. 2019 Jul 18;9(7):289. doi: 10.3390/biom9070289.
The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans.
DNA 甲基转移酶（DNMTs）活性的调节是一种重要的表观遗传机制，影响细胞中的基因表达或 DNA 修复机制。DNMTs 功能的异常修饰是人类癌症发病机制的一个基本事件和组成部分。植物次生代谢产物形式合成的植物化学物质是具有多种作用的生物分子的重要来源，从而提供了广泛的可能的临床应用。有充分的文献记载表明，植物化学物质具有显著的抗癌特性，在这方面，临床前研究中的快速发展令人鼓舞。植物化学物质影响几种表观遗传分子机制，包括 DNA 甲基化模式，如肿瘤抑制基因的过度甲基化和致癌基因的整体低甲基化，这些都是癌症发展和进展的特定细胞标志。这篇综述将重点介绍使用植物来源的化合物和植物性饮食来靶向表观遗传调节剂和基因转录调节剂的最新进展，以便在临床前和临床研究中生成新型抗癌药物作为常规治疗的增敏剂或适合高危人群化学预防临床环境的化合物。总之，已经描述了与适当调节 DNA 甲基化状态相关的膳食植物化学物质的不可争议的抗癌活性。然而，需要进行精心设计和良好控制的临床研究，以确认它们在人类长期消费后的有益的表观遗传效应。
