Untargeted Metabolomics Reveal Lipid Alterations upon 2-Deoxyglucose Treatment in Human HaCaT Keratinocytes

Area of Science:

• Biochemistry
• Cancer Biology
• Metabolomics

Background:

• 2-deoxyglucose (2-DG) is a glucose analogue investigated for anticancer properties.
• Its precise mechanism of action in cancer therapy remains incompletely understood.
• Understanding 2-DG's pharmacodynamics is crucial for its clinical application.

Purpose of the Study:

• To characterize the metabolic perturbations induced by 2-DG in human HaCaT keratinocytes.
• To elucidate the pharmacodynamics of 2-DG using a joint metabolomic and lipidomic approach.
• To identify key metabolites and pathways affected by 2-DG exposure.

Main Methods:

• Utilized an integrated UPLC-Q-Exactive-based metabolomic and lipidomic analysis.
• Employed XCMS data processing for feature detection and multivariate analysis.
• Performed metabolite identification and pathway analysis to interpret results.

Main Results:

• Identified eight significantly altered metabolites after 3 hours of 2-DG exposure.
• Lipidomic profiling revealed significant changes in ceramide and glucosylceramide derivatives.
• Metabolomic analysis indicated alterations in phosphatidylcholine and phosphatidylethanolamine derivatives.

Conclusions:

• The study highlights the significant impact of 2-DG on lipid metabolism, particularly ceramides.
• Findings suggest 2-DG's mechanism involves pathways related to cell death programming.
• The integrated analytical workflow effectively characterized 2-DG-induced metabolic changes, aiding in understanding its anticancer effects.