Yiannakopoulou Eugenia
Medical Laboratories, Faculty of Health and Caring Professions Technological Educational Institute of Athens, Eleutheriou Benizelou 106 Kallithea 17676, Athens, Greece,
Cell Oncol (Dordr). 2014 Jun;37(3):167-78. doi: 10.1007/s13402-014-0175-7. Epub 2014 Jul 5.
Epigenetic processes and miRNAs have been recognized as new targets for anticancer drug design. However, old multi-target drugs such as aspirin may also target epigenetic processes.
This review aims to provide an overview of our current knowledge on the modulation of epigenetic processes by aspirin and other non steroidal anti-inflammatory agents (NSAIDs) and their implications for cancer treatment and chemoprevention.
In vitro and in vivo studies, as well as primary patient data, suggest that aspirin and other NSAIDs reverse tumour suppressor gene hypermethylation in cancer tissues. It must be emphasized that, at this point in time, patient data are limited and DNA hypermethylation reversal has been investigated, but not tumour suppressor gene activation. In addition, evidence from experimental and patient data suggests that aspirin and NSAIDs may also reverse global DNA hypomethylation. At the histone level, both induction and inhibition of deacetylases by aspirin have been reported. Also, direct acetylation of histones by aspirin has been reported, while the natural salicylate anacardic acid has been found to inhibit histone acetyltransferase p300 both in vitro and in vivo, and to regulate gene expression through modulation of histone acetylation. Salicylates and other NSAIDs may also down-regulate miRNAs with oncogene-like functions or up-regulate miRNAs with tumour suppressor-like functions. Up till now, clinical trials have been aimed at investigating the effect of salicylates and NSAIDs on a limited number of miRNAs.
So, although the existing evidence is still limited, evidence is accumulating that epigenetic targets may represent nodal targets for the anti-proliferative actions of salicylates and NSAIDs. This, in turn, may have implications for cancer chemoprevention and treatment. Undoubtedly, this notion requires further investigation, but if proved correct, it could lead to the design of less toxic agents that target epigenetic processes as part of existing or novel multi-targeted treatment modalities.
表观遗传过程和微小RNA（miRNA）已被确认为抗癌药物设计的新靶点。然而，阿司匹林等传统多靶点药物也可能作用于表观遗传过程。
本综述旨在概述我们目前关于阿司匹林和其他非甾体抗炎药（NSAIDs）对表观遗传过程的调节作用及其在癌症治疗和化学预防中的意义的认识。
体外和体内研究以及患者原始数据表明，阿司匹林和其他NSAIDs可逆转癌组织中肿瘤抑制基因的高甲基化。必须强调的是，目前患者数据有限，且已对DNA高甲基化逆转进行了研究，但未对肿瘤抑制基因激活进行研究。此外，实验和患者数据的证据表明，阿司匹林和NSAIDs也可能逆转整体DNA低甲基化。在组蛋白水平上，已有报道称阿司匹林可诱导和抑制去乙酰化酶。此外，还报道了阿司匹林可直接使组蛋白乙酰化，而天然水杨酸盐漆树酸已被发现在体外和体内均可抑制组蛋白乙酰转移酶p300，并通过调节组蛋白乙酰化来调控基因表达。水杨酸盐和其他NSAIDs还可能下调具有癌基因样功能的miRNA或上调具有肿瘤抑制样功能的miRNA。到目前为止，临床试验旨在研究水杨酸盐和NSAIDs对有限数量miRNA的影响。
因此，尽管现有证据仍然有限，但越来越多的证据表明表观遗传靶点可能是水杨酸盐和NSAIDs抗增殖作用的关键靶点。这反过来可能对癌症化学预防和治疗产生影响。毫无疑问，这一观点需要进一步研究，但如果证明正确，可能会设计出毒性较小的药物，将表观遗传过程作为现有或新型多靶点治疗模式的一部分进行靶向治疗。
