Selim Khaled A, Abdelrasoul Hend, Aboelmagd Mohamed, Tawila Ahmed M
Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany.
Pharmaceutical and Drug Industries Research Division, National Research Centre, 33-El-Bohouth St. (former El Tahrir St.), Dokki, P.O. Box 12622, Giza, Egypt.
Diseases. 2017 Apr 26;5(2):13. doi: 10.3390/diseases5020013.
Reactive oxygen species (ROS) are common products of mitochondrial oxidative phosphorylation, xenobiotics metabolism and are generated in response to several environmental stress conditions. Some of them play important biochemical roles in cellular signal transduction and gene transcription. On the other hand, ROS are known to be involved in a wide range of human diseases, including cancer. The excessive production of such ROS together with disruption of homeostasis detoxifying mechanisms can mediate a series of cellular oxidative stresses. The oxidative stress of redundant free radicals production can lead to oxidative denaturation of cellular macromolecules including proteins, lipids and DNA. Moreover, oxidative damage is one of the major causes of DNA mutations, replication errors and genomic abnormalities which result in either inhibition or induction of transcription, and end with the disturbance of signal transduction pathways. Among affected signaling pathways are redox-sensitive kinases. The stimulation of these kinases induces several transcription factors through the phosphorylation of their module proteins. The activation of such pathways induces proliferation and cellular transformation. A diet rich in antioxidant compounds has potential health benefits, and there is a growing interest in the role of natural antioxidants in nutrition for prevention and cure of cancer diseases. A controversy has risen regarding the relation between antioxidants and the significant decrease in the risk of cancer incidence. In this review, we will focus on redox-sensitive kinases signaling pathways, highlighting the effects of dietary antioxidant on the prevention, incidence, prognosis or even treatment of human cancers. In addition, we will place emphasis on the chemical classes of pterocarpans as natural anti-oxidants/cancers as well as their underlying mechanisms of action, including their effects on MAPKs and topoisomerase activities.
活性氧（ROS）是线粒体氧化磷酸化和外源性物质代谢的常见产物，并且在应对多种环境应激条件时产生。其中一些在细胞信号转导和基因转录中发挥重要的生化作用。另一方面，已知ROS与包括癌症在内的多种人类疾病有关。此类ROS的过度产生以及体内平衡解毒机制的破坏可介导一系列细胞氧化应激。多余自由基产生的氧化应激可导致包括蛋白质、脂质和DNA在内的细胞大分子发生氧化变性。此外，氧化损伤是DNA突变、复制错误和基因组异常的主要原因之一，这些异常会导致转录的抑制或诱导，并最终导致信号转导通路的紊乱。受影响的信号通路中包括氧化还原敏感激酶。这些激酶的刺激通过其模块蛋白的磷酸化诱导多种转录因子。此类通路的激活诱导细胞增殖和转化。富含抗氧化化合物的饮食具有潜在的健康益处，并且人们对天然抗氧化剂在预防和治疗癌症疾病的营养作用的兴趣日益增加。关于抗氧化剂与癌症发病率显著降低之间的关系已经出现了争议。在本综述中，我们将聚焦于氧化还原敏感激酶信号通路，突出饮食抗氧化剂对人类癌症的预防、发病率、预后甚至治疗的影响。此外，我们将重点关注紫檀烷类作为天然抗氧化剂/抗癌剂的化学类别及其潜在的作用机制，包括它们对丝裂原活化蛋白激酶（MAPKs）和拓扑异构酶活性的影响。
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