ArticleScientific reports2018
Effects of metformin on colorectal cancer stem cells depend on alterations in glutamine metabolism.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 97 citations in OpenAlex.
- Mitochondrial dynamics: A promising tool for personalized TNBC management.Genes & diseases · 2026Review
- Glucose-induced histone lactylation confers metformin resistance in colorectal cancer stem cells.Nature communications · 2026Article
- Plumbagin Is a PKM2 Activator That Modulates Glutamine Metabolism and Dependency in Leukemia.Metabolites · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Metformin as a Multifaceted Therapeutic Agent for Gastrointestinal Diseases: Mechanisms, Clinical Efficacy, and Future Directions.Pharmacology research & perspectives · 2026Review
- RHOJ derived peptide promotes chemosensitivity by inhibiting glutamine metabolism in gastric cancer.Journal of translational medicine · 2026Article
- Identifying the therapeutic potential of niclosamide in overcoming IFN-gamma dependent cancer immune evasion in the tumor microenvironment.Frontiers in immunology · 2026Article
- Structural reassignment of compound 968, an allosteric glutaminase inhibitor.Beilstein journal of organic chemistry · 2026Article
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Impact of stool transplantation and metformin on polyp reduction and inflammation in an APC Min mouse model.Intestinal research · 2025Article
- Berberine Inhibits Breast Cancer Stem Cell Development and Decreases Inflammation: Involvement of miRNAs and IL-6.Current developments in nutrition · 2025Article
- Reprogramming of Glutamine Amino Acid Transporters Expression and Prognostic Significance in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
- Metabolic Rewiring in Cancer: Small Molecule Inhibitors in Colorectal Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Metformin and its potential influence on cell fate decision between apoptosis and senescence in cancer, with a special emphasis on glioblastoma.Frontiers in oncology · 2024Review
- Glutaminolysis is a Potential Therapeutic Target for Kidney Diseases.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- [Metformin inhibits self-renewal of colorectal cancer stem cells by inhibiting mitochondrial oxidative phosphorylation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer.Cancer communications (London, England) · 2023Article
- The role of tumor microenvironment on cancer stem cell fate in solid tumors.Cell communication and signaling : CCS · 2023Review
- Development of novel DNAJB6-KIAA1522-p-mTOR three-protein prognostic prediction models for CRC.Translational oncology · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin. A combination of metformin and glutaminase C inhibitor (compound 968) suppressed CSCs in SW620 cells and enhanced that effect in HT29 cells. SW620 cells showed higher expression of glutaminase 1 and glutamine transporter (ASCT2) than HT29 cells, especially ASCT2 in CSCs. Knockdown of glutaminase 1, ASCT2, and c-Myc induced significant CSC-suppression and enhanced CSC-suppressing effect of metformin and compound 968. In xenografts and human cancer organoids, combined treatment with metformin and compound 968 showed the same results as those shown in vitro. In conclusion, the effect of metformin on CSCs varies depending on the AMPK-mTOR and glutamine metabolism. The inhibition of glutamine pathway could enhance the CSC-suppressing effect of metformin, overcoming metformin resistance.
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