Department of Chemistry, University of Miami, Miami, FL-33146, USA.
Department of Biology, University of Miami, Miami, FL-33146, USA.
Chembiochem. 2023 Nov 2;24(21):e202300540. doi: 10.1002/cbic.202300540. Epub 2023 Sep 8.
Natural deep eutectic solvents (NADESs) are emerging sustainable alternatives to conventional organic solvents. Beyond their role as laboratory solvents, NADESs are increasingly explored in drug delivery and as therapeutics. Their increasing applications notwithstanding, our understanding of how they interact with biomolecules at multiple levels - metabolome, proteome, and transcriptome - within human cell remain poor. Here, we deploy integrated metabolomics, proteomics, and transcriptomics to probe how NADESs perturb the molecular landscape of human cells. In a human cell line model, we found that an archetypal NADES derived from choline and geranic acid (CAGE) significantly altered the metabolome, proteome, and transcriptome. CAGE upregulated indole-3-lactic acid and 4-hydroxyphenyllactic acid levels, resulting in ligand-independent activation of aryl hydrocarbon receptor to signal the transcription of genes with implications for inflammation, immunomodulation, cell development, and chemical detoxification. Further, treating the cell line with CAGE downregulated glutamine biosynthesis, a nutrient rapidly proliferating cancer cells require. CAGE's ability to attenuate glutamine levels is potentially relevant for cancer treatment. These findings suggest that NADESs, even when derived from natural components like choline, can indirectly modulate cell biology at multiple levels, expanding their applications beyond chemistry to biomedicine and biotechnology.
天然深共熔溶剂（NADESs）是一种新兴的可持续替代传统有机溶剂的方法。除了作为实验室溶剂的作用外，NADESs 还越来越多地被用于药物传递和治疗。尽管它们的应用越来越广泛，但我们对它们在人类细胞内如何在多个层面上与生物分子相互作用（代谢组、蛋白质组和转录组）的理解仍然很有限。在这里，我们采用整合的代谢组学、蛋白质组学和转录组学来探究 NADESs 如何扰乱人类细胞的分子图谱。在人类细胞系模型中，我们发现源自胆碱和金合欢酸（CAGE）的典型 NADES 显著改变了代谢组、蛋白质组和转录组。CAGE 上调了吲哚-3-乳酸和 4-羟基苯乳酸的水平，导致芳烃受体的配体非依赖性激活，从而转录与炎症、免疫调节、细胞发育和化学解毒有关的基因。此外，用 CAGE 处理细胞系会下调谷氨酰胺生物合成，而快速增殖的癌细胞需要这种营养物质。CAGE 降低谷氨酰胺水平的能力可能与癌症治疗有关。这些发现表明，即使 NADESs 是由胆碱等天然成分衍生而来，也可以在多个层面上间接调节细胞生物学，将它们的应用从化学扩展到生物医学和生物技术。
