School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK.
Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 5, rue J.-B. Clément, 92296, Châtenay-Malabry, France.
Chembiochem. 2022 May 18;23(10):e202100641. doi: 10.1002/cbic.202100641. Epub 2022 Jan 27.
Excessive cellular oxidative stress is widely perceived as a key factor in pathophysiological conditions and cancer development. Healthy cells use several mechanisms to maintain intracellular levels of reactive oxygen species (ROS) and overall redox homeostasis to avoid damage to DNA, proteins, and lipids. Cancer cells, in contrast, exhibit elevated ROS levels and upregulated protective antioxidant pathways. Counterintuitively, such elevated oxidative stress and enhanced antioxidant defence mechanisms in cancer cells provide a therapeutic opportunity for the development of drugs with different anticancer mechanisms of action (MoA). In this review, oxidative stress and the role of ROS in cells are described. The tumour-suppressive and tumour-promotive functions of ROS are discussed, and these two different therapeutic strategies (increasing or decreasing ROS to fight cancer) are compared. Clinically approved drugs with demonstrated oxidative stress anticancer MoAs are highlighted followed by description of examples of metal-based anticancer drug candidates causing oxidative stress in cancer cells via novel MoAs.
细胞内过度的氧化应激被广泛认为是病理生理状态和癌症发展的关键因素。健康细胞利用多种机制来维持细胞内活性氧（ROS）的水平和整体氧化还原平衡，以避免 DNA、蛋白质和脂质受损。相比之下，癌细胞表现出升高的 ROS 水平和上调的保护性抗氧化途径。矛盾的是，癌细胞中这种升高的氧化应激和增强的抗氧化防御机制为开发具有不同作用机制（MoA）的抗癌药物提供了治疗机会。在这篇综述中，描述了氧化应激和 ROS 在细胞中的作用。讨论了 ROS 在肿瘤抑制和促进中的作用，并比较了这两种不同的治疗策略（增加或减少 ROS 以对抗癌症）。重点介绍了具有已证实的氧化应激抗癌 MoA 的临床批准药物，随后描述了通过新型 MoA 在癌细胞中引起氧化应激的基于金属的候选抗癌药物的实例。
