Galadari Sehamuddin, Rahman Anees, Pallichankandy Siraj, Thayyullathil Faisal
Cell Signaling Laboratory, Department of Biochemistry, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE; Al Jalila Foundation Research Centre, P.O. Box 300100, Dubai, UAE.
Cell Signaling Laboratory, Department of Biochemistry, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE.
Free Radic Biol Med. 2017 Mar;104:144-164. doi: 10.1016/j.freeradbiomed.2017.01.004. Epub 2017 Jan 11.
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy. Therefore, increased ROS in cancer cells may provide a unique opportunity to eliminate cancer cells via elevating ROS to highly toxic levels intracellularly, thereby, activating various ROS-induced cell death pathways, or inhibiting cancer cell resistance to chemotherapy. Such results can be achieved by using agents that either increase ROS generation, or inhibit antioxidant defense, or even a combination of both. In fact, a large variety of anticancer drugs, and some of those currently under clinical trials, effectively kill cancer cells and overcome drug resistance via enhancing ROS generation and/or impeding the antioxidant defense mechanism. This review focuses on our current understanding of the tumor promoting (tumorigenesis, angiogenesis, invasion and metastasis, and chemoresistance) and the tumor suppressive (apoptosis, autophagy, and necroptosis) functions of ROS, and highlights the potential mechanism(s) involved. It also sheds light on a very novel and an actively growing field of ROS-dependent cell death mechanism referred to as ferroptosis.
活性氧（ROS）是一类高反应性离子和分子，越来越被视为参与多种生物过程调节的强大信号分子。事实上，它们在各种病理生理条件下的作用不断被阐明。例如，与正常细胞相比，癌细胞的ROS水平升高。这部分是由于癌细胞代谢增强和线粒体功能障碍。癌细胞中ROS生成的增加有助于肿瘤起始、促进和进展以及肿瘤对化疗的抵抗所必需的生化和分子变化。因此，癌细胞中ROS的增加可能提供一个独特的机会，即通过在细胞内将ROS升高到高毒性水平来消除癌细胞，从而激活各种ROS诱导的细胞死亡途径，或抑制癌细胞对化疗的抵抗。通过使用增加ROS生成、抑制抗氧化防御或两者结合的药物可以实现这样的结果。事实上，各种各样的抗癌药物，以及一些目前正在临床试验中的药物，通过增强ROS生成和/或阻碍抗氧化防御机制有效地杀死癌细胞并克服耐药性。本综述重点关注我们目前对ROS的肿瘤促进（肿瘤发生、血管生成、侵袭和转移以及化疗耐药）和肿瘤抑制（凋亡、自噬和坏死性凋亡）功能的理解，并突出其中涉及的潜在机制。它还揭示了一个非常新颖且正在积极发展的领域，即依赖ROS的细胞死亡机制——铁死亡。
