Department of Chemistry, Sookmyung Women's University, Seoul 04310, Korea.
Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, Korea.
J Am Chem Soc. 2023 Jul 26;145(29):16058-16068. doi: 10.1021/jacs.3c04414. Epub 2023 Jul 13.
Superoxide dismutases (SODs) are essential antioxidant enzymes that prevent massive superoxide radical production and thus protect cells from damage induced by free radicals. However, this concept has rarely been applied to directly impede the function of driver oncogenes, thus far. Here, leveraging efforts from SOD model complexes, we report the novel finding of biomimetic copper complexes that efficiently scavenge intracellularly generated free radicals and, thereby, directly access the core consequence of colorectal cancer suppression. We conceived four structurally different SOD-mimicking copper complexes that showed distinct disproportionation reaction rates of intracellular superoxide radical anions. By replenishing SOD models, we observed a dramatic reduction of intracellular reactive oxygen species (ROS) and adenine 5'-triphosphate (ATP) concentrations that led to cell cycle arrest at the G2/M stage and induced apoptosis in vitro and in vivo. Our results showcase how nature-mimicking models can be designed and fine-tuned to serve as a viable chemotherapeutic strategy for cancer treatment.
超氧化物歧化酶（SOD）是一种重要的抗氧化酶，可防止大量超氧自由基的产生，从而保护细胞免受自由基引起的损伤。然而，到目前为止，这一概念很少被直接用于阻碍驱动癌基因的功能。在这里，我们利用 SOD 模型配合物的研究成果，报告了一种新型仿生铜配合物的发现，该配合物能够有效地清除细胞内产生的自由基，从而直接抑制结直肠癌的核心后果。我们设计了四个结构不同的模拟 SOD 的铜配合物，它们具有不同的细胞内超氧阴离子歧化反应速率。通过补充 SOD 模型，我们观察到细胞内活性氧（ROS）和腺嘌呤 5'-三磷酸（ATP）浓度的急剧降低，导致细胞周期在 G2/M 期停滞，并在体外和体内诱导细胞凋亡。我们的结果展示了如何设计和微调模仿自然的模型，以作为癌症治疗的可行化疗策略。
