Shukla Samriddhi, Meeran Syed M, Katiyar Santosh K
Cancer Epigenetic Laboratory, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226021, India.
Department of Dermatology, University of Alabama, Birmingham, AL 35294, USA; Comprehensive Cancer Center, University of Alabama, Birmingham, AL 35294, USA; Birmingham Veterans Affairs Medical Center, Birmingham, AL 35233, USA.
Cancer Lett. 2014 Dec 1;355(1):9-17. doi: 10.1016/j.canlet.2014.09.017. Epub 2014 Sep 16.
The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy.
对癌症表观遗传学日益增长的兴趣很大程度上归因于表观遗传变化的可逆性,这种变化在致癌过程中往往会发生改变。主要的表观遗传变化包括DNA甲基化、染色质修饰和miRNA调控,它们在肿瘤发生过程中发挥着重要作用。有几种具有表观遗传活性的合成分子,如DNA甲基转移酶(DNMTs)和组蛋白脱乙酰酶(HDACs)抑制剂,它们要么已被批准,要么正在进行治疗各种癌症的临床试验。然而,大多数合成抑制剂都显示出不良副作用,特异性窄且价格昂贵。因此,具有生物活性的植物化学物质因其广泛可得且毒性较小,已被测试其在癌症预防和治疗的基因调控中表观遗传调节活性方面的作用。令人鼓舞的是,许多具有生物活性的植物化学物质通过调节癌症中的DNA甲基化和染色质修饰,潜在地改变了关键肿瘤抑制基因、肿瘤促进基因和癌基因的表达。这些具有生物活性的植物化学物质单独或与其他植物化学物质联合使用,对各种癌症都显示出了有前景的结果。在此,我们总结并讨论一些常见研究的植物化学物质的作用及其在癌症预防和癌症治疗中特别受关注的表观遗传靶点。