Эпигаллокатехин и рак
жүктеу/скачать 1.88 Mb.
|
- Бұл бет үшін навигация:
- Эпигенетические механизмы
- Эпигенетические диетические соединений
- Будущая перспектива
- Epigenetic mechanisms
Будущая перспективаРазличных механизмов, участвующих в поддержании эпигенетического государств. Исследований, обсуждаемых в данном документе показали, что пищевые факторы, которые, вероятно, способствуют эпигенетических изменений, а в некоторых случаях может быть возможность обратного аномальные эпигенетических состояний. Кроме того, в то время как многие из вышеупомянутых исследований были проведены с использованием определенного диетического фактора, есть основания полагать, что большинство может быть использован в комбинации и на протяжении всей жизни. Это может предоставить обоснование для изучения питательных эпигенетические более модификаторов в сочетании исследований или предложение " эпигенетические диета " фокусируется на употреблении продуктов, которые показывают способность стимулировать выгодно эпигенетических модификаций, в том числе увеличение потребления фруктов, овощей и те пищевые компоненты, которые упоминаются в настоящем документе. Это может использоваться от химические точки зрения включения противораковых питательных веществ в одной ежедневной рутины, чтобы препятствовать механизмов болезни. С терапевтической точки зрения многих питательных веществ были и изучаются их способность предотвратить и уменьшить риск или тяжесть некоторых заболеваний и для их антиканцерогенные свойства. Области нутригеномики предполагает изучение того, как гены и пищевые компоненты взаимодействуют влиять на фенотип и может показать, как один реагирует на биологически активные компоненты, основанные на генетике, питательных веществ-индуцированные изменения в метилировании ДНК и хроматина изменения, и питательных-индуцированные изменения в экспрессии генов, в то время как области nutriepigenomics предполагает непрерывное ремоделирования нашей epigenomes, пищевые факторы [218-220]. Nutriepigenomic исследований, ориентируясь на индивидуальные ответы в биологически активные компоненты и индивидуальный эпигенетические диеты, состоящей из биологически активных пищевых факторов, упомянутых в настоящем документе, будет представлять особый интерес в будущем. Кроме того, будущие исследования, посвященные изучению клинической значимости и механизм эпигенетической модификации био-активные пищевые факторы необходимы для дальнейшей оценки применимости диетических факторов рака профилактические и химические агенты. Резюме
Эпигенетические диетические соединений
Будущая перспектива
Dietary factors have become agents of strong interest in the field of epigenetics. A number of bioactive dietary components that appear to have potential to prevent disease and promote overall health have been identified [1–4]. In fact, several naturally occurring dietary phytochemicals have been demonstrated to have anticarcinogenic properties and may play a role in regulating biological processes [5,6]. Many studies have shown that natural products have epigenetic targets in cancer cells and can act as cancer preventive agents. Compounds found in dietary phytochemical preparations such as teas, garlic, soy products, herbs, grapes and cruciferous vegetables are now generally accepted to defend against the development of many different types of tumors as well as acting as epigenetic modulators that impact not only the initiation, but also the progression of oncogenesis [6–9]. Epigenetic mechanismsThe term epigenetics was coined in 1942 by developmental biologist Conrad H Waddington [10]. Epigenetics generally refers to heritable changes in gene expression and chromatin organization that are not due to alterations in the DNA sequence [11]. Epigenetic modifications typically occur by changes in DNA methylation, histone covalent modifications or by RNAi [12]. DNA methylation occurs when a methyl group is added to the 5-carbon (C5) position of a cytosine. The methylation of cytosine involves the transfer of a methyl group from S-adenosyl-L-methionine (SAM), a methyl precursor, to the cytosines in CpG dinucleotides [13]. DNA methylation has many roles in various cellular processes and may impact the transcription of genes by preventing the binding of key transcriptional factors [14–17]. Transcriptional silencing due to DNA methylation is thought to occur by the recruitment of methyl CpG-binding transcriptional repressors and by interfering with the DNA binding of transcriptional activators, which in turn results in a condensed chromatin state. In addition, methylated DNA may be bound by methyl-CpG-binding domain (MBD) proteins, which are essential for binding to 5-methylcytosine [16]. DNA methylation is catalyzed by enzymes known as DNA methyltransferases (DNMTs) and hypermethylation of CpG dinucleotides or CpG islands by DNMTs usually results in transcriptional gene silencing and gene inactivation [12]. The human genome contains four DNMT genes, DNMT1, DNMT2, DNMT3A and DNMT3B [18]. Altered DNMT expression and activity is seen in numerous diseases including autism, cardiovascular diseases, obesity, Type-2 diabetes and cancer [19–23]. In addition, global hypomethylation is associated with nearly all human cancers [24,25]. Histone modifications typically occur as post-translational modifications at the N-terminal of histones. These modifications include acetylation, methylation, phosphorylation, biotinylation and ubiquitination and are essential during development [26–28]. Histone modifications are catalyzed by enzymes such as histone methyltransferases (HMTs), histone demethylases (HDMs) histone acetyltransferases (HATs), and histone deacetylases (HDACs). HMTs act to add methyl groups to lysine and/or arginine residues in histones, while HDMs remove the methyl moieties. In turn, HATs catalyze the addition of acetyl groups to the lysine residues of histones, whereas HDACs are responsible for the removal of these groups [29,30]. Lysine methylation can cause either activation or repression of transcription, while arginine methylation typically activates transcription. Likewise, histone hyperacetylation results in the activation of normally repressed genes while hypoacetylation results in gene silencing. This is apparent in carcinogenesis where aberrant activity of HATs and HDACs are thought to trigger carcinogenic processes [31]. RNAi is the process by which dsRNA inhibits the accumulation of homologous transcripts from like genes [32]. RNAi or ncRNAs, in the form of antisense transcripts, can lead to transcriptional silencing by the formation of heterochromatin. The involvement of RNA in different silencing mechanisms has been described in detail in several organisms [33]. For example, in the yeast Schizosaccharomyces pombe, the deletion of different components of the RNAi machinery results in the loss of H3K9 methylation, as well as impairment of centromere function [33,34]. Similarly, DNA methylation and H3K9 methylation have been demonstrated in Arabidopsis thaliana and in α-thalassaemia [35,36]. RNAi has also been demonstrated to be involved in silencing genes associated with HIV-1, along with several types of cancers [37–41]. In addition, noncoding miRNAs can control the expression of DNMTs and other enzymes associated with epigenetic modifications, which affect mRNA translation and stability [42–44]. Exciting developments have indicated that RNAi-directed silencing of heterochromatic regions might trigger direct histone modifications and DNA methylation to specific loci, causing gene silencing [35,36,45,46]. Epigenetic modifications are of particular interest in the field of cancer research since their impact on the epigenome is involved in cell proliferation, differentiation and survival [27,47,48]. Furthermore, epigenetic modifications are often involved in transcriptional regulation and have been implicated both in tumor development and progression [40,49,50]. Epigenetic modifications causing transcriptional deregulation may result in the inappropriate expression or activation of transcription factors associated with oncogenes and/or the failure to express genes responsible for tumor suppression [51]. In fact, cancer cells have genome-wide aberrations in a number of epigenetic markers, including global hypomethylation, global downregulation of miRNAs, promoter-specific hypermethylation, histone deacetylation and upregulation of epigenetic machinery [52]. In addition, the impact of epigenomic processes in cancer is apparent by the finding that at least half of all tumor suppressor genes are inactivated through epigenetic mechanisms in tumorigenesis [16,53–55]. Bioactive dietary components consumed by ingesting natural products including fruits and vegetables can act as sources of vitamins and minerals. While this is an invaluable role, these agents have high potential for application to oncogenesis owing to in part to their anticarcinogenic properties [9,56]. A growing body of evidence suggests that dietary agents as well as non-nutrient components of fruits and vegetables can affect epigenetic processes and are involved in processes, including the reactivation of tumor suppressor genes, the initiation of apoptosis, the repression of cancer-related genes and the activation of cell survival proteins in different cancers [57–60]. Dietary phytochemicals such as tea polyphenols, genistein, sulforaphane (SFN), resveratrol, curcumin and others have been demonstrated to be effective agents against cancer and to act through epigenetic mechanisms that affect the epigenome [56,61]. жүктеу/скачать 1.88 Mb. Достарыңызбен бөлісу:
|