Yan Hao-Xin, Zhang Yi-Zhong, Niu Yu-Qing, Wang Yu-Wei, Liu Li-Hua, Tang Yu-Ping, Huang Ju-Min, Leung Elaine Lai-Han
State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics of Innovative Drug Discovery, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau (SAR), PR China.
Cancer Center, Faculty of Health Sciences, University of Macau, Macau (SAR), China. MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau (SAR), PR China.
Phytomedicine. 2025 Feb;137:156377. doi: 10.1016/j.phymed.2025.156377. Epub 2025 Jan 6.
Drug resistance in cancer is steadily rising, making the development of new therapeutic targets increasingly critical for improving treatment outcomes.
The mutual regulation of ions is essential for cell growth. Based on this concept, ion interference strategies offer a highly effective approach for cancer treatment. Calcium ions (Ca), as major second messengers, are closely associated with ion exchange and homeostasis. Disruptions in this balance can lead to cell death. However, while iron ions are also crucial, the connection between Caand iron-induced cell death (ferroptosis) has not been well established. Therefore, this study suggests that Ca may play a role in the induction of ferroptosis, presenting a novel and efficient target for cancer therapy.
PubMed, Google Scholar, and Web of Science databases were systematically searched for articles published in the past 15 years on the mechanisms of calcium ion-induced ferroptosis in cancer and related drugs.
The analysis highlights how Caregulate ferroptosis. The mechanisms by which Cainfluence ferroptosis are summarized based on existing literature, and relevant drugs that act on Ca/ferroptosis axis are outlined.
Ca regulate ferroptosis primarily through the modulation of reactive oxygen species (ROS) and glutathione (GSH) levels, a mechanism that applies to a wide range of cancer cells as well as paracancerous and normal cells in cancer treatment. Furthermore, plant-derived active compounds exhibit potent anticancer properties and often act on the Ca/ferroptosis axis. These natural compounds could play a significant role in the development of new cancer treatment strategies.
癌症中的耐药性正在稳步上升,因此开发新的治疗靶点对于改善治疗效果变得越来越关键。
离子的相互调节对细胞生长至关重要。基于这一概念,离子干扰策略为癌症治疗提供了一种高效的方法。钙离子(Ca)作为主要的第二信使,与离子交换和体内平衡密切相关。这种平衡的破坏会导致细胞死亡。然而,虽然铁离子也很关键,但钙离子与铁诱导的细胞死亡(铁死亡)之间的联系尚未完全确立。因此,本研究表明钙离子可能在铁死亡的诱导中起作用,为癌症治疗提供了一个新的有效靶点。
系统检索了PubMed、谷歌学术和科学网数据库中过去15年发表的关于钙离子诱导癌症铁死亡机制及相关药物的文章。
分析突出了钙离子如何调节铁死亡。根据现有文献总结了钙离子影响铁死亡的机制,并概述了作用于钙/铁死亡轴的相关药物。
钙离子主要通过调节活性氧(ROS)和谷胱甘肽(GSH)水平来调节铁死亡,这一机制适用于广泛的癌细胞以及癌症治疗中的癌旁细胞和正常细胞。此外,植物来源的活性化合物具有强大的抗癌特性,且常常作用于钙/铁死亡轴。这些天然化合物可能在新的癌症治疗策略开发中发挥重要作用。