Vieri Walter, Ghini Veronica, Turano Paola, Massai Lara, Messori Luigi, Fondi Marco
Department of Biology, University of Florence, Florence, Italy.
Department of Biology, University of Naples Federico II, Via Cinthia, 26 - 80126 Naples, Italy and Department of Agriculture, Food, Environment and Forestry (DAGRI), University of Florence, Florence, Italy.
NPJ Syst Biol Appl. 2025 Jul 28;11(1):83. doi: 10.1038/s41540-025-00535-9.
Gold compounds are a promising class of experimental anticancer metallodrugs. Unlike platinum-based drugs, their antiproliferative effects are thought to result mainly from modulation of cancer cell metabolism rather than direct interaction with DNA. Previous NMR studies have shown that four cytotoxic gold compounds - auranofin, aurothiomalate and two gold N-heterocyclic carbenes - induce distinct metabolic changes in A2780 ovarian cancer cells, suggesting the occurrence of different mechanisms of action. To better understand these effects, we constructed a genome-scale metabolic model (GEM) of A2780 cells to analyze the NMR-detected metabolomic changes. The model successfully predicts the diverse metabolic responses induced by each gold compound and identifies common metabolic changes. These results confirm the potential of GEMs as a powerful tool for interpreting and predicting cellular responses to gold-based drugs, providing insights into their mechanisms of action and potential therapeutic applications.
金化合物是一类很有前景的实验性抗癌金属药物。与铂类药物不同，它们的抗增殖作用被认为主要源于对癌细胞代谢的调节，而非与DNA的直接相互作用。先前的核磁共振研究表明，四种具有细胞毒性的金化合物——金诺芬、硫代苹果酸金钠和两种金氮杂环卡宾——在A2780卵巢癌细胞中诱导出不同的代谢变化，这表明存在不同的作用机制。为了更好地理解这些效应，我们构建了A2780细胞的基因组规模代谢模型（GEM），以分析核磁共振检测到的代谢组学变化。该模型成功预测了每种金化合物诱导的不同代谢反应，并识别出常见的代谢变化。这些结果证实了基因组规模代谢模型作为解释和预测细胞对金基药物反应的强大工具的潜力，为其作用机制和潜在治疗应用提供了见解。
