Dietary Sulforaphane, a Histone Deacetylase Inhibitor for Cancer Prevention
Dietary Sulforaphane, a Histone Deacetylase Inhibitor for Cancer Prevention
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DOI：
10.3945/jn.109.113332
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Dashwood, Roderick H.
中科院分区：
文献类型：
--
作者：
Ho, Emily;Clarke, John D.;Dashwood, Roderick H.
组蛋白的可逆乙酰化是基因调控的重要机制。在前列腺癌进展过程中，组蛋白上乙酰化模式的特定修饰是明显的。针对表观基因组，包括使用组蛋白脱乙酰酶(HDAC)抑制剂，是一种新的癌症化学预防策略。最近，被归类为HDAC抑制剂的药物在癌症临床试验中显示出了良好的前景。我们之前已经发现萝卜硫素(SFN)，一种在十字花科蔬菜中发现的化合物，可以抑制人类结直肠和前列腺癌细胞中的HDAC活性。基于SFN代谢物和其他植物化学物质与已知的HDAC抑制剂的相似性，我们先前证明萝卜硫素在前列腺癌中起HDAC抑制剂的作用，导致组蛋白乙酰化增强，P21和Bax下调，并诱导细胞周期停滞/凋亡，从而预防癌症。SFN针对异常乙酰化模式的能力，以及对第二阶段酶的影响，可能使其成为一种有效的化学预防药物，这些研究之所以重要，是因为这些研究有可能鉴定或改变对高危前列腺癌患者的建议，从而通过将容易获得的食物加入到他们的饮食中来提高他们的存活率。这些研究也将为未来大规模的人类临床干预研究提供坚实的科学基础。J.Nutr.139：2393-2396,2009。
The reversible acetylation of histones is an important mechanism of gene regulation. During prostate cancer progression, specific modifications in acetylation patterns on histones are apparent. Targeting the epigenome, including the use of histone deacetylase (HDAC) inhibitors, is a novel strategy for cancer chemoprevention. Recently, drugs classified as HDAC inhibitors have shown promise in cancer clinical trials. We have previously found that sulforaphane (SFN), a compound found in cruciferous vegetables, inhibits HDAC activity in human colorectal and prostate cancer cells. Based on the similarity of SFN metabolites and other phytochemicals to known HDAC inhibitors, we previously demonstrated that sulforaphane acted as an HDAC inhibitor in the prostate, causing enhanced histone acetylation, derepression of P21 and Bax, and induction of cell cycle arrest/apoptosis, leading to cancer prevention. The ability of SFN to target aberrant acetylation patterns, in addition to effects on phase 2 enzymes, may make it an effective chemoprevention agent, These studies are important because of the potential to qualify or change recommendations for high-risk prostate cancer patients and thereby increase their survival through simple dietary choices incorporating easily accessible foods into their diets. These studies also will provide a strong scientific foundation for future large-scale human clinical intervention studies. J. Nutr. 139: 2393-2396, 2009.