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

IF 3.5 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Metabolomics Pub Date : 2024-10-05 DOI:10.1007/s11306-024-02179-y

Wentao Zhu, John A Lusk, Vadim Pascua, Danijel Djukovic, Daniel Raftery

{"title":"Combination of low glucose and SCD1 inhibition impairs cancer metabolic plasticity and growth in MCF-7 cancer cells: a comprehensive metabolomic and lipidomic analysis.","authors":"Wentao Zhu, John A Lusk, Vadim Pascua, Danijel Djukovic, Daniel Raftery","doi":"10.1007/s11306-024-02179-y","DOIUrl":null,"url":null,"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.","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11306-024-02179-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

低糖与 SCD1 抑制相结合损害 MCF-7 癌细胞的癌症代谢可塑性和生长：代谢组学和脂质组学综合分析。

背景：癌细胞表现出显著的代谢可塑性，使其能够适应波动的营养条件。本研究探讨了低葡萄糖水平和使用 A939572 抑制硬脂酰-CoA 去饱和酶 1（SCD1）对癌症代谢可塑性和生长的影响：方法：为了揭示细胞代谢物和脂质的复杂变化，我们进行了全面的代谢组学和脂质组学分析。将 MCF-7 细胞置于低糖条件下，使用 A939572 抑制 SCD1。研究人员探讨了由此引起的代谢途径和脂质谱的变化，以阐明对癌细胞生理机能的协同作用：结果：低糖与 A939572 诱导的 SCD1 抑制相结合，显著削弱了癌细胞的代谢可塑性。代谢组学分析突显了关键糖酵解和氨基酸通路的变化，表明细胞在努力适应受限的葡萄糖供应。脂质组分析揭示了脂质组成的改变，这意味着膜完整性和信号级联遭到破坏：我们的研究结果强调了葡萄糖供应和 SCD1 活性在维持癌症代谢可塑性和生长中的关键作用。同时靶向这些通路是阻止癌症进展的一种有前途的策略。全面的代谢组学和脂质组学分析为这种联合疗法所诱导的分子改变提供了详细的路线图，可能有助于确定潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Metabolomics 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.80%

发文量

审稿时长

2 months

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.