摘要
背景:表观遗传调节(如组蛋白修饰)因其修饰基因而不改变DNA序列的能力而日益受到重视。已经显示许多生物活性化合物改变各种癌症中的遗传和表观遗传学特征。 Sulforaphane(SFN)是十字花科蔬菜中发现的异硫氰酸盐,如羽衣甘蓝,卷心菜和西兰花芽,是迄今为止最有效的组蛋白去乙酰化酶抑制剂(HDACis)之一。最近,已经确定HDAC在调节微RNA(miR)和人端粒酶逆转录酶(hTERT)中可能发挥重要作用。 目的:我们的研究目标是确定异常的HDAC,hTERT和miR水平是否可以通过在结肠直肠癌(CRC)细胞中采用基于饮食的新方法来调节。 方法:采用MTT法,细胞密度实验,实时逆转录 - 聚合酶链反应(RT-PCR),细胞周期分析,western-blot实验,HDAC活性实验和免疫组织化学方法检测SFN对CRC细胞的体外表观遗传效应。 teloTAGGG端粒酶PCR Elisa分析。 结果:我们在HCT116和RKO CRC细胞中证明了生理相关浓度SFN的抑制作用,并首次表明SFN处理降低了CRC细胞的细胞密度,显着抑制了细胞活力并诱导细胞凋亡。我们还发现实际剂量的SFN显着下调CRC细胞中的致癌miR-21,HDAC和hTERT mRNA,蛋白质和酶水平。 结论:我们的研究表明HDAC,hTERT和miR-21的调控是延缓和/或预防CRC的有希望的方法,并且可以通过在十字花科蔬菜中食用SFN来完成。
关键词: Sulforaphane,表观遗传学,组蛋白去酰化酶,组蛋白去质酶抑制剂,人端粒酶逆转录酶,miR-21。
Current Cancer Drug Targets
Title:Mechanisms for the Inhibition of Colon Cancer Cells by Sulforaphane through Epigenetic Modulation of MicroRNA-21 and Human Telomerase Reverse Transcriptase (hTERT) Down-regulation
Volume: 18 Issue: 1
关键词: Sulforaphane,表观遗传学,组蛋白去酰化酶,组蛋白去质酶抑制剂,人端粒酶逆转录酶,miR-21。
摘要: Background: Epigenetic modulations such as histone modifications are becoming increasingly valued for their ability to modify genes without altering the DNA sequence. Many bioactive compounds have been shown to alter genetic and epigenetic profiles in various cancers. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables such as kale, cabbage and broccoli sprouts, is one of the most potent histone deacetylase inhibitors (HDACis) to date. Recently, it has been identified that HDACis may play a vital role in regulating microRNAs (miRs) and human telomerase reverse transcriptase (hTERT).
Objective: The aim of our study was to identify if aberrant HDAC, hTERT and miR levels could be regulated through novel dietary-based approaches in colorectal cancer (CRC) cells.
Methods: We evaluated the in vitro epigenetic effects of SFN on CRC cells by MTT assay, cellular density assay, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), cell cycle analysis, western-blot assay, HDAC activity assay and teloTAGGG telomerase PCR Elisa assay.
Results: We demonstrated the inhibitory effects of physiologically relevant concentrations of SFN in both HCT116 and RKO CRC cells, and showed for the first time that SFN treatment decreased cell density, significantly inhibited cell viability and induced apoptosis in CRC cells. We also found that practical doses of SFN significantly down-regulated oncogenic miR-21, HDAC and hTERT mRNA, protein and enzymatic levels in CRC cells.
Conclusion: Our studies suggest that the regulation of HDAC, hTERT and miR-21 is a promising approach for delaying and/or preventing CRC and may be accomplished via the consumption of SFN in cruciferous vegetables.
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Mechanisms for the Inhibition of Colon Cancer Cells by Sulforaphane through Epigenetic Modulation of MicroRNA-21 and Human Telomerase Reverse Transcriptase (hTERT) Down-regulation, Current Cancer Drug Targets 2018; 18 (1) . https://dx.doi.org/10.2174/1568009617666170206104032
DOI https://dx.doi.org/10.2174/1568009617666170206104032 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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