PDF(Pubmed)
Abstract：
Ferroptosis is a distinct mode of cell death, distinguishing itself from typical apoptosis by its reliance on the accumulation of iron ions and lipid peroxides. Cells manifest an imbalance between oxidative stress and antioxidant equilibrium during certain pathological contexts, such as tumours, resulting in oxidative stress. Notably, recent investigations propose that heightened intracellular reactive oxygen species (ROS) due to oxidative stress can heighten cellular susceptibility to ferroptosis inducers or expedite the onset of ferroptosis. Consequently, comprehending role of ROS in the initiation of ferroptosis has significance in elucidating disorders related to oxidative stress. Moreover, an exhaustive exploration into the mechanism and control of ferroptosis might offer novel targets for addressing specific tumour types. Within this context, our review delves into recent fundamental pathways and the molecular foundation of ferroptosis. Four classical ferroptotic molecular pathways are well characterized, namely, glutathione peroxidase 4-centred molecular pathway, nuclear factor erythroid 2-related factor 2 molecular pathway, mitochondrial molecular pathway, and mTOR-dependent autophagy pathway. Furthermore, we seek to elucidate the regulatory contributions enacted by ROS. Additionally, we provide an overview of targeted medications targeting four molecular pathways implicated in ferroptosis and their potential clinical applications. Here, we review the role of ROS and oxidative stress in ferroptosis, and we discuss opportunities to use ferroptosis as a new strategy for cancer therapy and point out the current challenges persisting within the domain of ROS-regulated anticancer drug research and development.
摘要：
铁死亡是一种独特的细胞死亡模式，通过依赖铁离子和脂质过氧化物的积累来区别于典型的细胞凋亡。在某些病理背景下，细胞表现出氧化应激和抗氧化平衡之间的失衡，比如肿瘤，导致氧化应激。值得注意的是,最近的研究表明，由于氧化应激引起的细胞内活性氧（ROS）的增加可以提高细胞对铁凋亡诱导剂的敏感性或加速铁凋亡的发生。因此,了解ROS在铁凋亡启动中的作用对阐明与氧化应激相关的疾病具有重要意义。此外，对铁死亡的机制和控制的详尽探索可能为解决特定肿瘤类型提供新的靶标。在此背景下,我们的综述探讨了最近的基本途径和铁性凋亡的分子基础。四个经典的铁分子途径被很好地表征，即,谷胱甘肽过氧化物酶4中心分子途径，核因子红系2相关因子2分子途径，线粒体分子途径，和mTOR依赖性自噬途径。此外，我们试图阐明ROS制定的监管贡献。此外,我们概述了针对铁凋亡的4种分子途径的靶向药物及其潜在的临床应用.这里,我们综述了ROS和氧化应激在铁死亡中的作用，我们讨论了将铁凋亡作为癌症治疗新策略的机会，并指出了当前在ROS调节的抗癌药物研究和开发领域中持续存在的挑战。
