You Yawen, Guo Zhaochen, Wolter Tyler, Hu Quanyin
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin Madison, Madison, WI 53705, USA.
Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Chem Soc Rev. 2025 Feb 3;54(3):1552-1582. doi: 10.1039/d4cs00930d.
Intracellular metal ions play essential roles in multiple physiological processes, including catalytic action, diverse cellular processes, intracellular signaling, and electron transfer. It is crucial to maintain intracellular metal ion homeostasis which is achieved by the subtle balance of storage and release of metal ions intracellularly along with the influx and efflux of metal ions at the interface of the cell membrane. Dysregulation of intracellular metal ions has been identified as a key mechanism in triggering programmed cell death (PCD). Despite the importance of metal ions in initiating PCD, the molecular mechanisms of intracellular metal ions within these processes are infrequently discussed. An in-depth understanding and review of the role of metal ions in triggering PCD may better uncover novel tools for cancer diagnosis and therapy. Specifically, the essential roles of calcium (Ca), iron (Fe), copper (Cu), and zinc (Zn) ions in triggering PCD are primarily explored in this review, and other ions like manganese (Mn), cobalt (Co) and magnesium ions (Mg) are briefly discussed. Further, this review elaborates on the underlying chemical mechanisms and summarizes these metal ions triggering PCD in cancer therapy. This review bridges chemistry, immunology, and biology to foster the rational regulation of metal ions to induce PCD for cancer therapy.
细胞内金属离子在多种生理过程中发挥着重要作用，包括催化作用、各种细胞过程、细胞内信号传导和电子转移。维持细胞内金属离子稳态至关重要，这是通过细胞内金属离子储存和释放的微妙平衡以及细胞膜界面处金属离子的流入和流出实现的。细胞内金属离子失调已被确定为触发程序性细胞死亡（PCD）的关键机制。尽管金属离子在引发PCD中很重要，但这些过程中细胞内金属离子的分子机制却很少被讨论。深入理解和综述金属离子在触发PCD中的作用可能会更好地揭示癌症诊断和治疗的新工具。具体而言，本综述主要探讨钙（Ca）、铁（Fe）、铜（Cu）和锌（Zn）离子在触发PCD中的重要作用，并简要讨论锰（Mn）、钴（Co）和镁离子（Mg）等其他离子。此外，本综述阐述了潜在的化学机制，并总结了这些金属离子在癌症治疗中触发PCD的情况。本综述将化学、免疫学和生物学联系起来，以促进对金属离子的合理调控，从而诱导PCD用于癌症治疗。
