Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
Eur J Nutr. 2013 Jun;52(4):1327-41. doi: 10.1007/s00394-012-0442-1. Epub 2012 Aug 26.
It is relatively unknown how different dietary components, in partnership, regulate gene expression linked to colon pathology. It has been suggested that the combination of various bioactive components present in a plant-based diet is crucial for their potential anticancer activities. This study employed a combinatorial chemopreventive strategy to investigate the impact of selenium and/or isothiocyanates on DNA methylation processes in colorectal carcinoma cell lines.
To gain insights into the epigenetic-mediated changes in gene expression in response to these dietary constituents cultured Caco-2 and HCT116 cells were exposed for up to 12 days to different concentrations of selenium methylselenocysteine and selenite (ranging from 0.2 to 5 μM) either alone or in combination with sulforaphane and iberin (ranging from 6 to 8 μM), and changes to gene-specific (p16(INK4A) and ESR1), global (LINE-1) methylation and DNMT expression were quantified using real-time PCR-based assays.
No effects on the methylation of CpG islands in ESR1, p16(INK4A) or of LINE-1, a marker of global genomic methylation, were observed after exposure of Caco-2 and HCT116 cells to selenium or isothiocyanates. Only transient changes in DNMT mRNA expression, which occurred mostly in the treatment groups containing isothiocyanates, were observed, and these occurred only for specific DNMT transcripts and did not lead to the modification of the aberrant methylation status present in these cells.
These data suggest that treatment for colon cancer cells with selenium and/or isothiocyanates, either individually or in combination does not impact abnormal methylation patterns of key genes involved in the complex multistep process of colon carcinogenesis in vitro.
不同的饮食成分如何协同调节与结肠病理相关的基因表达尚不清楚。有人认为，植物性饮食中各种生物活性成分的组合对于它们的潜在抗癌活性至关重要。本研究采用组合化学预防策略，研究硒和/或异硫氰酸盐对结直肠癌细胞系中 DNA 甲基化过程的影响。
为了深入了解这些饮食成分对基因表达的表观遗传介导变化，我们将培养的 Caco-2 和 HCT116 细胞暴露于不同浓度的硒甲基硒代半胱氨酸和亚硒酸钠（范围为 0.2 至 5 μM）中，单独或与萝卜硫素和异长春花碱（范围为 6 至 8 μM）组合，使用基于实时 PCR 的测定法来量化基因特异性（p16(INK4A)和 ESR1）、全基因组（LINE-1）甲基化和 DNMT 表达的变化。
Caco-2 和 HCT116 细胞暴露于硒或异硫氰酸盐后，未观察到 ESR1、p16(INK4A)或 LINE-1（全基因组甲基化的标志物）CpG 岛的甲基化变化。仅观察到 DNMT mRNA 表达的短暂变化，这些变化主要发生在含有异硫氰酸盐的治疗组中，但这些变化仅针对特定的 DNMT 转录本，并且不会导致这些细胞中存在的异常甲基化状态发生改变。
这些数据表明，单独或联合使用硒和/或异硫氰酸盐治疗结肠癌细胞不会影响涉及结肠癌变复杂多步骤过程的关键基因的异常甲基化模式。
