Different mechanisms are involved in the maintenance of epigenetic states. Studies discussed herein have shown that dietary factors are likely to contribute to epigenetic alterations and in some cases may be able to reverse abnormal epigenetic states. In addition, while many of the aforementioned studies were conducted using a particular dietary factor, it is reasonable to believe that most may be consumed in combination and over a period of a lifetime. This may provide a rationale for studying nutrient epigenetic modifiers more in combination studies or the proposal of an ‘epigenetic diet’ focused on consuming products that show the ability to stimulate beneficial epigenetic modifications, including increased consumption of fruit, vegetables and those dietary components that are mentioned herein. This may be used from a chemopreventive standpoint to incorporate anticancer nutrients into one’s daily routine to impede disease mechanisms. From a therapeutic perspective many nutrients have been and are being studied for their ability to prevent and reduce the risk or severity of certain diseases and for their anticarcinogenic properties. The field of nutrigenomics involves studying how genes and dietary components interact to influence phenotype and can reveal how one responds to bioactive components based on genetics, nutrient-induced changes in DNA methylation and chromatin alterations, and nutrient-induced changes in gene expression, whereas the field of nutriepigenomics involves the lifelong remodeling of our epigenomes by nutritional factors [218–220]. Nutriepigenomic studies focusing on individual responses to bioactive components and individualized epigenetic diets consisting of bioactive dietary factors mentioned herein will be of particular interest in the future. Furthermore, future studies focusing on the clinical relevance and mechanism of epigenetic modification of bio-active dietary factors are needed to further assess the applicability of dietary factors as cancer preventive and chemopreventive agents.
Executive summary
Epigenetic mechanisms -
Epigenetic modifications typically occur by changes in DNA methylation, histone modifications, or by RNAi and can be influenced by dietary factors.
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At least a half of all tumor suppressor genes are inactivated through epigenetic mechanisms in tumorigenesis.
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Evidence suggests that dietary agents can affect epigenetic processes.
Epigenetic diet compounds -
Dietary polyphenols such as tea polyphenols (i.e., epicatechin, epicatechin-3-gallate, epigallocatechin and epigallocatechin-3-gallate), resveratrol and curcumin can inhibit DNA methyltransferases and act as histone modifiers and demonstrate potential as anticancer therapeutic as well as chemopreventive agents.
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Isoflavones such as genistein are found in soybeans, fava beans and kudzu and have been demonstrated to have anticancer properties that, in part, involve DNA methylation.
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Isothiocyanates including sulforaphane are known to affect the epigenome and to have anticancer properties and act as a histone deacetylase inhibitor.
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Other dietary factors including those found in Brazilian nuts, chicken, cereals, coffee, cashews, garlic, parsley, milk thistle and rosemary, have also been reported to have epigenetic targets in cancer. While most natural dietary products have shown beneficial effects on the epigenome, some dietary components (i.e., alcohol) are associated with harmful epigenetic modifications.
Future perspective -
Many nutrients have been and are being studied for their chemopreventive and/or chemotherapeutic properties.
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Numerous investigations provide a rationale for studying nutrient epigenetic modifiers further in combination studies. Furthermore, the proposal of an ‘epigenetic diet’ focused on consuming products that show the ability to stimulate beneficial epigenetic modifications will be of particular interest in the future.
Катехин зеленого чая, эпигаллокатехин-3-галлат (EGCG): механизмы и перспективы клинического применения.
Расширение тело доклинические данные свидетельствуют, EGCG, основной катехин, содержащийся в зеленых чая (Camellia sinensis), имеет потенциал для воздействия разнообразных заболеваний человека. Видимо, EGCG действует как мощный антиоксидант, предотвращая окислительное повреждение здоровых клеток, но также в качестве антиангиогенных и противоопухолевого агента и в качестве модулятора опухоли клеточный ответ на химиотерапию. Много рака химические свойства зеленого чая, которые проводятся при посредничестве EGCG, который индуцирует апоптоз и способствует росту клеток ареста путем изменения экспрессии белков, регулирующих клеточный цикл, активация убийца каспаз, и подавляя онкогенные факторы транскрипции и поддержания плюрипотентности факторов. In vitro исследования показали, что EGCG блокирует канцерогенеза, воздействуя на широкий спектр путей передачи сигнала, включая JAK/STAT, MAPK, PI3K/AKT, Wnt и Notch. EGCG стимулирует теломер фрагментации путем ингибирования активности теломеразы. Различные клинические исследования показали, что лечение EGCG подавляет опухоли, распространенности и многочисленности в разных органа сайтов, таких как печени, желудка, кожи, легких, молочной железы и толстой кишки. Последние работы показали, что EGCG снижение DNMTs, протеазы, и DHFR деятельности, которые влияют на транскрипцию Гцр и синтез белка. EGCG обладает большим потенциалом в рак предотвращение из-за его безопасности, низкой стоимости и биодоступность. В этом обзоремы рассмотрим ее раком - профилактические свойства и механизм его действия на многочисленных пунктов, регулирующих рак рост клеток, выживаемость, ангиогенеза и метастазирования. Поэтому, нетоксичный природный агент может быть полезен либо в одиночку, либо в сочетании с обычными терапии для профилактики прогрессии опухоли и/или лечения злокачественных опухолей человека.
Biochem Pharmacol. 2011 Dec 15;82(12):1807-21. doi: 10.1016/j.bcp.2011.07.093. Epub 2011 Jul 30.
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