College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
School of Chemistry, Central China Normal University, Wuhan 430079, China.
Molecules. 2021 Dec 27;27(1):148. doi: 10.3390/molecules27010148.
Reactive oxygen species (ROS) are rapidly eliminated and reproduced in organisms, and they always play important roles in various biological functions and abnormal pathological processes. Evaluated ROS have frequently been observed in various cancers to activate multiple pro-tumorigenic signaling pathways and induce the survival and proliferation of cancer cells. Hydrogen peroxide (HO) and superoxide anion (O) are the most important redox signaling agents in cancer cells, the homeostasis of which is maintained by dozens of growth factors, cytokines, and antioxidant enzymes. Therefore, antioxidant enzymes tend to have higher activity levels to maintain the homeostasis of ROS in cancer cells. Effective intervention in the ROS homeostasis of cancer cells by chelating agents or metal complexes has already developed into an important anti-cancer strategy. We can inhibit the activity of antioxidant enzymes using chelators or metal complexes; on the other hand, we can also use metal complexes to directly regulate the level of ROS in cancer cells via mitochondria. In this review, metal complexes or chelators with ROS regulation capacity and with anti-cancer applications are collectively and comprehensively analyzed, which is beneficial for the development of the next generation of inorganic anti-cancer drugs based on ROS regulation. We expect that this review will provide a new perspective to develop novel inorganic reagents for killing cancer cells and, further, as candidates or clinical drugs.
活性氧 (ROS) 在生物体中迅速被清除和产生，它们在各种生物功能和异常病理过程中始终发挥着重要作用。在各种癌症中，评估 ROS 经常被观察到，它可以激活多种促肿瘤发生的信号通路，并诱导癌细胞的存活和增殖。过氧化氢 (HO) 和超氧阴离子 (O) 是癌细胞中最重要的氧化还原信号剂，它们的内稳态由数十种生长因子、细胞因子和抗氧化酶维持。因此，抗氧化酶往往具有更高的活性水平，以维持癌细胞中 ROS 的内稳态。通过螯合剂或金属配合物有效干预癌细胞的 ROS 内稳态已经发展成为一种重要的抗癌策略。我们可以使用螯合剂或金属配合物抑制抗氧化酶的活性；另一方面，我们还可以通过线粒体直接使用金属配合物来调节癌细胞中 ROS 的水平。在这篇综述中，对具有 ROS 调节能力和抗癌应用的金属配合物或螯合剂进行了全面的综合分析，这有利于基于 ROS 调节的下一代无机抗癌药物的开发。我们希望这篇综述能为开发新型的杀伤癌细胞的无机试剂提供一个新的视角，并进一步作为候选药物或临床药物。
