Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen, Germany.
German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center, D-35392 Giessen, Germany.
Int J Mol Sci. 2017 Oct 17;18(10):2160. doi: 10.3390/ijms18102160.
Epigenetic inactivation of tumor suppressor genes (TSG) is a fundamental event in the pathogenesis of human cancer. This silencing is accomplished by aberrant chromatin modifications including DNA hypermethylation of the gene promoter. One of the most frequently hypermethylated TSG in human cancer is the () gene. Aberrant methylation of has been reported in melanoma, sarcoma and carcinoma of different tissues. hypermethylation has been correlated with tumor progression and poor prognosis. Reactivation of epigenetically silenced TSG has been suggested as a therapy in cancer treatment. In particular, natural compounds isolated from herbal extracts have been tested for their capacity to induce in cancer cells, through demethylation. Here, we review the treatment of cancer cells with natural supplements (e.g., methyl donors, vitamins and polyphenols) that have been utilized to revert or prevent the epigenetic silencing of . Moreover, we specify pathways that were involved in reactivation. Several of these compounds (e.g., reseveratol and curcumin) act by inhibiting the activity or expression of DNA methyltransferases and reactive in cancer. Thus natural compounds could serve as important agents in tumor prevention or cancer therapy. However, the exact epigenetic reactivation mechanism is still under investigation.
肿瘤抑制基因 (TSG) 的表观遗传失活是人类癌症发病机制的一个基本事件。这种沉默是通过异常的染色质修饰来实现的，包括基因启动子的 DNA 过度甲基化。在人类癌症中最常发生过度甲基化的 TSG 之一是 () 基因。已经在黑色素瘤、肉瘤和不同组织的癌中报道了 的异常甲基化。 的异常甲基化与肿瘤进展和预后不良相关。已经提出了重新激活表观遗传沉默的 TSG 作为癌症治疗的一种疗法。特别是，已经测试了从草药提取物中分离出的天然化合物通过去甲基化来诱导癌细胞中的 。在这里，我们回顾了用天然补充剂（例如供甲基体、维生素和多酚）治疗癌细胞的情况，这些补充剂已被用于逆转或预防 的表观遗传沉默。此外，我们还指定了涉及 重新激活的途径。这些化合物中的几种（例如白藜芦醇和姜黄素）通过抑制 DNA 甲基转移酶和反应性 的活性或表达来发挥作用。因此，天然化合物可以作为肿瘤预防或癌症治疗的重要药物。然而，确切的表观遗传再激活机制仍在研究中。
