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组蛋白去乙酰化酶抑制剂(I 类)、癌症干细胞和植物化学物质:癌症治疗和预防的意义。

HDACis (class I), cancer stem cell, and phytochemicals: Cancer therapy and prevention implications.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Biomed Pharmacother. 2018 Jan;97:1445-1453. doi: 10.1016/j.biopha.2017.11.065. Epub 2017 Dec 14.

Abstract

Epigenetics is independent of the sequence events that physically affect the condensing of chromatin and genes expression. The unique epigenetic memories of various cells trigger exclusive gene expression profiling. According to different studies, the aberrant epigenetic signatures and impaired gene expression profiles are master occurrences in cancer cells in which oncogene and tumor suppressor genes are affected. Owing to the facts that epigenetic modifications are performed earlier than expression and are reversible, the epigenetic reprogramming of cancer cells could be applied potentially for their prevention, control, and therapy. The disruption of the acetylation signature, as a master epigenetic change in cancers, is related to the expression and the activity of HDACs. In this context, class I HDACs play a significant role in the regulation of cell proliferation and cancer. More recently, cancer stem cell (CSC) has been introduced as a minority population of tumor that is responsible for invasiveness, drug resistance, and relapse of cancers. It is now believed that controlling CSC via epigenetic reprogramming such as targeting HDACs could be helpful in regulating the acetylation pattern of chromatin. Recently, a number of reports have introduced some phytochemicals as HDAC inhibitors. The use of phytochemicals with the HDAC inhibition property could be potentially efficient in overcoming the mentioned problems of CSCs. This review presents a perspective concerning HDAC-targeted phytochemicals to control CSC in tumors. Hopefully, this new route would have more advantages in therapeutic applications and prevention against cancer.

摘要

表观遗传学独立于物理影响染色质浓缩和基因表达的序列事件。各种细胞独特的表观遗传记忆引发独特的基因表达谱。根据不同的研究,异常的表观遗传特征和受损的基因表达谱是癌细胞中的主要发生事件,其中癌基因和肿瘤抑制基因受到影响。由于表观遗传修饰发生在表达之前并且是可逆的,因此癌细胞的表观遗传重编程可能潜在地用于预防、控制和治疗癌症。作为癌症中主要的表观遗传变化,乙酰化特征的破坏与 HDACs 的表达和活性有关。在这种情况下,I 类 HDAC 在细胞增殖和癌症的调节中起着重要作用。最近,癌症干细胞(CSC)被引入为肿瘤的少数群体,负责侵袭、耐药和癌症复发。现在人们相信,通过表观遗传重编程(如靶向 HDACs)来控制 CSC,可以有助于调节染色质的乙酰化模式。最近,许多报告介绍了一些植物化学物质作为 HDAC 抑制剂。使用具有 HDAC 抑制特性的植物化学物质可能在克服 CSC 所提到的问题方面非常有效。这篇综述介绍了针对 HDAC 的植物化学物质来控制肿瘤中的 CSC 的观点。希望这条新途径在治疗应用和预防癌症方面具有更多优势。

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