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Epigenetic Mechanisms Underlying Diet-Sourced Compounds in the Prevention and Treatment of Gastrointestinal Cancer

机译:胃肠癌预防和治疗中饮食中的表观遗传机制

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摘要

The development of colon cancer, the third most diagnosed cancer and third leading cause of cancer deaths in the United States, can be influenced by genetic predispositions and environmental exposures. As 80% of colon cancer cases are sporadic in nature, much interest lies in determining risk factors that may foster its development, as well as identifying compounds that could inhibit colon cancer development or halt progression. A major risk factor for sporadic colon cancer is a high fat, Western diet which has been linked to a cancer-prone, pro-inflammatory state. Cultures which place an emphasis on fresh fruits and vegetables demonstrate lower colon cancer incidences. Diet not only has the potential to encourage colon cancer development, but recent evidence demonstrates that certain dietary natural products can halt colon cancer development and progression via epigenetic regulation. Epigenetic dysregulation may contribute to inflammation-driven diseases, such as cancer, and can lead to the inappropriate silencing of genes necessary to inhibit cancer development. Natural compounds have shown the ability to reverse epigenetic dysregulation in in vitro and in vivo models. As current allopathic medicines aimed at reversing epigenetic silencing are accompanied with the risk of toxicity and side effects, much interest lies in being able to harness the disease preventing properties in natural products. Here, we discuss the epidemiology of colon cancer, describe the need for natural approaches to inhibit disease development and highlight natural products which have been shown to inhibit gastrointestinal cancer initiation and progression in vitro or in vivo through epigenetic modulation.
机译:结肠癌是美国第三大被诊断为癌症且是癌症死亡的第三大主要原因,其发展可能受到遗传易感性和环境暴露的影响。由于80%的结肠癌病例是散发性疾病,因此人们非常关注确定可能促进其发展的危险因素,以及确定可抑制结肠癌发展或阻止进展的化合物。散发性结肠癌的主要危险因素是高脂肪的西方饮食,这种饮食与容易发生癌症的促炎状态有关。注重新鲜水果和蔬菜的文化显示出较低的结肠癌发病率。饮食不仅具有促进结肠癌发展的潜力,而且最近的证据表明某些饮食天然产物可以通过表观遗传调控阻止结肠癌的发展和进程。表观遗传失调可能导致炎症驱动的疾病,例如癌症,并可能导致抑制癌症发展所必需的基因被不适当地沉默。天然化合物在体外和体内模型中已显示出逆转表观遗传失调的能力。由于当前旨在逆转表观遗传沉默的同种疗法药物具有毒性和副作用的风险,因此人们对利用天然产物中的疾病预防特性抱有极大的兴趣。在这里,我们讨论了结肠癌的流行病学,描述了对抑制疾病发展的自然方法的需求,并着重介绍了天然产物,这些天然产物已被证明可以通过表观遗传调控体外或体内抑制胃肠道癌的发生和发展。

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