Mitochondrial ROS and cancer drug resistance: Implications for therapy.
Mitochondrial ROS and cancer drug resistance: Implications for therapy.
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DOI：
10.1016/j.phrs.2015.06.013
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发表时间：
2015-10
影响因子：
9.3
通讯作者：
Zou MH
中科院分区：
文献类型：
--
作者：
Okon IS;Zou MH
在生理条件下，存在一个协调良好且平衡的氧化还原系统，以确保活性氧物质（ROS）被恰当地利用来实现特定功能，比如信号传导和蛋白质调节。活性氧在恶性细胞中的影响是好是坏可能取决于几个因素，例如肿瘤和组织类型、疾病阶段、治疗策略，以及活性氧的持续时间、特异性和水平。那么活性氧在癌症中已知的作用是什么呢？首先，活性氧显著影响癌症表型。其次，负责杀死癌细胞的活性氧的氧化特性也影响次级信号网络。第三，活性氧与可能促进突变的基因不稳定性之间存在很强的相关性。最后，新出现的观察结果表明线粒体活性氧在癌症耐药性中起作用，这对治疗有影响。线粒体是癌细胞内代谢 - 氧化还原（代谢氧化还原）变化的关键调节因子。就像一把双刃剑，癌症治疗中的线粒体活性氧扰动可能是有益的，也可能是有害的。然而，利用针对癌症的活性氧特异性益处仍然是一个重大挑战。
Under physiological conditions, a well-coordinated and balanced redox system exists to ensure that reactive oxygen species (ROS) are appropriately utilized to accomplish specific functions, such as signaling and protein regulation. The influence of ROS within malignant cells, whether for good or bad may depend on several factors, such as tumor and tissue type, disease stage, treatment strategy, as well as duration, specificity and levels of ROS. What then are the known roles of ROS in cancer? Firstly, ROS significantly impacts cancer phenotypes. Secondly, the oxidative ROS property responsible for killing cancer cells, also impact secondary signaling networks. Thirdly, a strong correlation exist between ROS and genetic instability which may promote mutations. Finally, emerging observations suggest a role for mitochondrial ROS in cancer drug resistance, with implications for therapy. The mitochondria is a key regulator of metabolic-redox (meta-redox) alterations within cancer cells. Like a double-edged sword, mitochondrial ROS perturbations in cancer therapy may be beneficial or detrimental. However, harnessing ROS-specific cancer-targeting benefits remain a major challenge.