Ligand‐Independent Activation of Aryl Hydrocarbon Receptor and Attenuation of Glutamine Levels by Natural Deep Eutectic Solvent

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 the...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2023-11, Vol.24 (21), p.e202300540-e202300540
Main Authors: Denis, Amina Anaise, Toledo, Daniela, Hakim, Queen Assala, Quintana, Aline Andrea, Escobar, Catalina Real, Oluwole, Samuel Abidemi, Costa, Arthur, Garcia, Estefania Gil, Hill, Anaya Rose, Agatemor, Christian
Format: Article
Language:English
Subjects:
Aromatic compounds
Biomolecules
Biosynthesis
Biotechnology
Cages
Cancer
Cancer therapies
Choline
Detoxification
Down-regulation
Drug delivery
Glutamine
Hydrocarbons
Immunomodulation
Lactic acid
Ligands
Metabolomics
Organic solvents
Proteomes
Proteomics
Receptors
Solvents
Transcriptomes
Transcriptomics
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Summary: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.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.202300540