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

Abstract : The glucose analogue 2-deoxyglucose (2-DG) impedes cancer progression in animal models and is currently being assessed as an anticancer therapy, yet the mode of action of this drug of high clinical significance has not been fully delineated. In an attempt to better characterize its pharmacodynamics, an integrative UPLC-Q-Exactive-based joint metabolomic and lipidomic approach was undertaken to evaluate the metabolic perturbations induced by this drug in human HaCaT keratinocyte cells. R-XCMS data processing and subsequent multivariate pattern recognition, metabolites identification, and pathway analyses identified eight metabolites that were most significantly changed upon a 3 h 2-DG exposure. Most of these dysregulated features were emphasized in the course of lipidomic profiling and could be identified as ceramide and glucosylceramide derivatives, consistently with their involvement in cell death programming. Even though metabolomic analyses did not generally afford such clear-cut dysregulations, some alterations in phosphatidylcholine and phosphatidylethanolamine derivatives could be highlighted as well. Overall, these results support the adequacy of the proposed analytical workflow and might contribute to a better understanding of the mechanisms underlying the promising effects of 2-DG.
Document type :
Journal articles
Complete list of metadatas

Cited literature [80 references]  Display  Hide  Download

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01730281
Contributor : Xavier Chard-Hutchinson <>
Submitted on : Friday, July 6, 2018 - 9:25:32 AM
Last modification on : Thursday, July 11, 2019 - 1:01:59 AM
Long-term archiving on : Tuesday, October 2, 2018 - 4:24:26 AM

File

Le Pogam et al_2018_Untargeted...
Files produced by the author(s)

Identifiers

Citation

Pierre Le Pogam, Mickael Doué, Yann Le Page, Denis Habauzit, Maxim Zhadobov, et al.. Untargeted Metabolomics Reveal Lipid Alterations upon 2-Deoxyglucose Treatment in Human HaCaT Keratinocytes. Journal of Proteome Research, American Chemical Society, 2018, 17 (3), pp.1146-1157. ⟨10.1021/acs.jproteome.7b00805⟩. ⟨hal-01730281⟩

Share

Metrics

Record views

1007

Files downloads

229