title: Unraveling the cytotoxicity and metabolic pathways of binary natural deep eutectic solvent systems.
abstract: In this study, the anticancer potential and cytotoxicity of natural deep eutectic solvents (NADESs) were assessed using HelaS3, PC3, A375, AGS, MCF-7, and WRL-68 hepatic cell lines. NADESs were prepared from choline chloride, fructose, or glucose and compared with an N,N-diethyl ethanolammonium chloride:triethylene glycol DES. The NADESs (98 ≤ EC50≥ 516 mM) were less toxic than the DES (34 ≤ EC50≥ 120 mM). The EC50values of the NADESs were significantly higher than those of the aqueous solutions of their individual components but were similar to those of the aqueous solutions of combinations of their chief elements. Due to the uniqueness of these results, the possibility that NADESs could be synthesized intracellularly to counterbalance the cytotoxicity of their excess principal constituents must be entertained. However, further research is needed to explore this avenue. NADESs exerted cytotoxicity by increasing membrane porosity and redox stress. In vivo, they were more destructive than the DES and induced liver failure. The potential of these mixtures was evidenced by their anticancer activity and intracellular processing. This infers that they can serve as tools for increasing our understanding of cell physiology and metabolism. It is likely that we only have begun to comprehend the nature of NADESs.
authors.affiliation: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur 50603, Malaysia.|Department of Chemical Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Yves Paul
authors.initials: YP
authors.lastname: Mbous
authors.affiliation: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur 50603, Malaysia.|Institute of Halal Research University of Malaya (IHRUM), Academy of Islamic studies, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Maan
authors.initials: M
authors.lastname: Hayyan
authors.affiliation: Department of Medical Microbiology, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Won Fen
authors.initials: WF
authors.lastname: Wong
authors.affiliation: Department of Pharmacology, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur 50603, Malaysia.|Department of Chemical Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Mohd Ali
authors.initials: MA
authors.lastname: Hashim
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005632:Fructose / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012997:Solvents / Q000737:chemistry / Q000633:toxicity*; D014783:Viscosity
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D012997:Solvents; D005632:Fructose; D005947:Glucose