DNA甲基化（DNA methylation）是最早发现的修饰途径之一，大量研究表明，DNA甲基化能引起染色质结构、DNA构象、DNA稳定性及DNA与蛋白质相互作用方式的改变，从而控制基因表达。DNA甲基化是关闭基因通道的正常操作过程，有助于调控细胞获取DNA基因信息。在癌症疾病中，DNA甲基化进程被打乱。其他一些疾病如心血管疾病、免疫功能低下、神经变性疾病等患者体内同样也存在着DNA甲基化进程紊乱现象。
近日，俄亥俄州立大学研究人员在Clin Epigenetics杂志上发表的一项研究文章揭示：在西兰花、芥蓝、北方圆红萝卜等十字花科植物中含量较丰富的萝卜硫素(1-异硫氰酸-4-甲磺酰基丁烷) (Sulforaphane)的两条抗癌机制。
萝卜硫素，又称“莱菔硫烷”，是目前发现的所有天然抗癌物质里，效力最强、效果最好的活性成分，其有独特的抗癌功效，它可以造成癌细胞的细胞凋亡和细胞阻滞，同时可以诱导人体内的Ⅱ相解毒酶，同时抑制Ⅰ型酶的产生，最终通过多种酶体系排出致癌物和自由基等有害成分，同时，该成分不会在人体内残留，对机体无副作用，是一种新型的抗癌成分。
DNA甲基化以及组蛋白去乙酰化酶(histone deacetylase, HDAC)对细胞功能和细胞的分裂发挥重要作用。通常DNA甲基化以及HDAC被抑制被当作是癌症发生的标志。先前研究发现萝卜硫素作为HDAC抑制剂能修复修复正确的平衡，抑制肿瘤细胞的生长。在这项研究中，工作人员发现萝卜硫素也能作用于前列腺癌细胞D2细胞周期蛋白的去甲基化过程，抑制前列腺癌细胞增殖。
研究人员表示：西兰花等其他的一些十字花科蔬菜中含有大量的萝卜硫素，不管实验室研究还是临床上研究都证实了多摄入西兰花等十字花科蔬菜有助于防癌。（生物谷Bioon.com）
doi:10.1186/1868-7083-3-3
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Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells
Anna Hsu,1,2 Carmen P Wong,1,2 Zhen Yu,3 David E Williams,2,3 Roderick H Dashwood,2,3 and Emily Hocorresponding author1,2
Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC) enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent.
