Oxidative stress induced lung cancer and COPD: opportunities for epigenetic therapy.
Oxidative stress induced lung cancer and COPD: opportunities for epigenetic therapy.
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DOI：
10.1111/j.1582-4934.2009.00845.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Gray SG
中科院分区：
文献类型：
--
作者：
Lawless MW;O'Byrne KJ;Gray SG
活性氧（ROS）是氧正常代谢的天然副产物，在细胞内发挥重要作用。在正常情况下，细胞能够在ROS的形成和通过特定的酶途径或通过抗氧化剂去除ROS之间保持足够的稳态。然而，如果这种平衡被打破，就会发生氧化应激。重要的是，氧化应激在包括癌症在内的许多疾病的发病机制中起重要作用。表观遗传学是基因表达受遗传机制调节的过程，这些机制不会导致DNA序列本身的任何直接变化，并且表观遗传机制的破坏在疾病中具有重要意义。有证据表明，组蛋白脱乙酰酶（HDAC）在调节重要的细胞氧化应激途径中起决定性作用，包括参与感受氧化应激的途径和参与调节细胞对氧化应激的反应的途径。特别是HDAC对这些通路的异常调节可能在癌症进展中起关键作用。在这篇综述中，我们讨论了目前的证据将表观遗传学和氧化应激与癌症联系起来，使用慢性阻塞性肺疾病和非小细胞肺癌来说明表观遗传学在这些疾病环境中对这些途径的重要性。
Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell. Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants. If however, this balance is disturbed a situation called oxidative stress occurs. Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer. Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease. Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression. In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings.