Combination of low glucose and SCD1 inhibition impairs cancer metabolic plasticity and growth in MCF-7 cancer cells: a comprehensive metabolomic and lipidomic analysis.
Wentao Zhu, John A Lusk, Vadim Pascua, Danijel Djukovic, Daniel Raftery
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Abstract
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.
期刊介绍：
Metabolomics publishes current research regarding the development of technology platforms for metabolomics. This includes, but is not limited to:
metabolomic applications within man, including pre-clinical and clinical
pharmacometabolomics for precision medicine
metabolic profiling and fingerprinting
metabolite target analysis
metabolomic applications within animals, plants and microbes
transcriptomics and proteomics in systems biology
Metabolomics is an indispensable platform for researchers using new post-genomics approaches, to discover networks and interactions between metabolites, pharmaceuticals, SNPs, proteins and more. Its articles go beyond the genome and metabolome, by including original clinical study material together with big data from new emerging technologies.
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