Combination of low glucose and SCD1 inhibition impairs cancer metabolic plasticity and growth in MCF-7 cancer cells: a comprehensive metabolomic and lipidomic analysis.

Autor: Zhu W; Northwest Metabolomics Research Center, Seattle, WA, USA.; Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington, Seattle, WA, USA., Lusk JA; Northwest Metabolomics Research Center, Seattle, WA, USA.; Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington, Seattle, WA, USA., Pascua V; Northwest Metabolomics Research Center, Seattle, WA, USA.; Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington, Seattle, WA, USA., Djukovic D; Northwest Metabolomics Research Center, Seattle, WA, USA.; Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington, Seattle, WA, USA., Raftery D; Northwest Metabolomics Research Center, Seattle, WA, USA. draftery@uw.edu.; Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington, Seattle, WA, USA. draftery@uw.edu.; Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. draftery@uw.edu.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2024 Oct 05; Vol. 20 (5), pp. 112. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1007/s11306-024-02179-y
Abstrakt: Background: Cancer cells exhibit remarkable metabolic plasticity, enabling them to adapt to fluctuating nutrient conditions. This study investigates the impact of a combination of low glucose levels and inhibition of stearoyl-CoA desaturase 1 (SCD1) using A939572 on cancer metabolic plasticity and growth.
Methods: A comprehensive metabolomic and lipidomic analysis was conducted to unravel the intricate changes in cellular metabolites and lipids. MCF-7 cells were subjected to low glucose conditions, and SCD1 was inhibited using A939572. The resulting alterations in metabolic pathways and lipid profiles were explored to elucidate the synergistic effects on cancer cell physiology.
Results: The combination of low glucose and A939572-induced SCD1 inhibition significantly impaired cancer cell metabolic plasticity. Metabolomic analysis highlighted shifts in key glycolytic and amino acid pathways, indicating the cells' struggle to adapt to restricted glucose availability. Lipidomic profiling revealed alterations in lipid composition, implying disruptions in membrane integrity and signaling cascades.
Conclusion: Our findings underscore the critical roles of glucose availability and SCD1 activity in sustaining cancer metabolic plasticity and growth. Simultaneously targeting these pathways emerges as a promising strategy to impede cancer progression. The comprehensive metabolomic and lipidomic analysis provides a detailed roadmap of molecular alterations induced by this combination treatment, that may help identify potential therapeutic targets.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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