Mukherjee Neelam, Kumar Addanki P, Ghosh Rita
Department of Urology, School of Medicine, University of Texas Health Science Center at San Antonio.
Department of Urology, School of Medicine, University of Texas Health Science Center at San Antonio ; Department of Pharmacology, School of Medicine, University of Texas Health Science Center at San Antonio ; Department of Molecular Medicine, School of Medicine, University of Texas Health Science Center at San Antonio ; South Texas Veterans Health Care System, San Antonio, TX 78229.
Curr Pharmacol Rep. 2015 Apr 1;1(2):112-120. doi: 10.1007/s40495-014-0004-8.
Malignancies of the genitourinary system have some of the highest cancer incidence and mortality rates. For example prostate cancer is the second most common cancer in men and ovarian cancer mortality and incidence are near equal. In addition to genetic changes modulation of the epigenome is critical to cancer development and progression. In this regard epigenetic changes in DNA methylation state and DNA hypermethylation in particular has garnered a great deal of attention. While hypomethylation occurs mostly in repeated sequence such as tandem and interspersed repeats and segment duplications, hypermethylation is associated with CpG islands. Hypomethylation leads to activation of cancer-causing genes with global DNA hypomethylation being commonly associated with metastatic disease. Hypermethylation-mediated silencing of tumor suppressive genes is commonly associated with cancer development. Bioactive phytochemicals such as flavonoids present in fruits, vegetables, beverages etc. have the ability to modulate DNA methylation status and are therefore very valuable agents for cancer prevention. In this review we discuss several commonly methylated genes and flavonoids used to modulate DNA methylation in the prevention of genitourinary cancers.
泌尿生殖系统恶性肿瘤的癌症发病率和死亡率位居前列。例如,前列腺癌是男性第二常见的癌症,卵巢癌的死亡率和发病率几乎相当。除了基因变化外,表观基因组的调控对癌症的发生和发展至关重要。在这方面,DNA甲基化状态的表观遗传变化,尤其是DNA高甲基化,已引起了广泛关注。虽然低甲基化主要发生在重复序列中,如串联重复、散布重复和片段重复,但高甲基化与CpG岛相关。低甲基化会导致致癌基因的激活,而整体DNA低甲基化通常与转移性疾病有关。高甲基化介导的肿瘤抑制基因沉默通常与癌症发展有关。水果、蔬菜、饮料等中含有的生物活性植物化学物质,如黄酮类化合物,具有调节DNA甲基化状态的能力,因此是预防癌症的非常有价值的物质。在这篇综述中,我们讨论了几种常用于调节DNA甲基化以预防泌尿生殖系统癌症的常见甲基化基因和黄酮类化合物。