DNA甲基化(DNA methylation)是最早發(fā)現(xiàn)的修飾途徑之一,,大量研究表明,,DNA甲基化能引起染色質(zhì)結(jié)構(gòu),、DNA構(gòu)象,、DNA穩(wěn)定性及DNA與蛋白質(zhì)相互作用方式的改變,,從而控制基因表達(dá),。DNA甲基化是關(guān)閉基因通道的正常操作過(guò)程,有助于調(diào)控細(xì)胞獲取DNA基因信息,。在癌癥疾病中,,DNA甲基化進(jìn)程被打亂,。其他一些疾病如心血管疾病、免疫功能低下,、神經(jīng)變性疾病等患者體內(nèi)同樣也存在著DNA甲基化進(jìn)程紊亂現(xiàn)象,。
近日,俄亥俄州立大學(xué)研究人員在Clin Epigenetics雜志上發(fā)表的一項(xiàng)研究文章揭示:在西蘭花,、芥藍(lán),、北方圓紅蘿卜等十字花科植物中含量較豐富的蘿卜硫素(1-異硫氰酸-4-甲磺酰基丁烷) (Sulforaphane)的兩條抗癌機(jī)制,。
蘿卜硫素,,又稱“萊菔硫烷”,是目前發(fā)現(xiàn)的所有天然抗癌物質(zhì)里,,效力最強(qiáng),、效果最好的活性成分,其有獨(dú)特的抗癌功效,,它可以造成癌細(xì)胞的細(xì)胞凋亡和細(xì)胞阻滯,,同時(shí)可以誘導(dǎo)人體內(nèi)的Ⅱ相解毒酶,同時(shí)抑制Ⅰ型酶的產(chǎn)生,,最終通過(guò)多種酶體系排出致癌物和自由基等有害成分,,同時(shí),該成分不會(huì)在人體內(nèi)殘留,,對(duì)機(jī)體無(wú)副作用,,是一種新型的抗癌成分。
DNA甲基化以及組蛋白去乙?;?histone deacetylase, HDAC)對(duì)細(xì)胞功能和細(xì)胞的分裂發(fā)揮重要作用,。通常DNA甲基化以及HDAC被抑制被當(dāng)作是癌癥發(fā)生的標(biāo)志。先前研究發(fā)現(xiàn)蘿卜硫素作為HDAC抑制劑能修復(fù)修復(fù)正確的平衡,,抑制腫瘤細(xì)胞的生長(zhǎng),。在這項(xiàng)研究中,工作人員發(fā)現(xiàn)蘿卜硫素也能作用于前列腺癌細(xì)胞D2細(xì)胞周期蛋白的去甲基化過(guò)程,,抑制前列腺癌細(xì)胞增殖,。
研究人員表示:西蘭花等其他的一些十字花科蔬菜中含有大量的蘿卜硫素,不管實(shí)驗(yàn)室研究還是臨床上研究都證實(shí)了多攝入西蘭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.