ArticleProceedings of the National Academy of Sciences of the United States of America2014
Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 1 of them a synthesis that pooled it.
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Who cites it
180 citing papers in PubMed, 1 synthesis or guideline pooled it, 260 citations in OpenAlex.
- Metformin Use on Incidence and Oncologic Outcomes of Bladder Cancer Patients With T2DM: An Updated Meta-Analysis.Frontiers in pharmacology · 2022Pooled it
- Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2020Trial
- Genetic landscape of an in vivo protein interactome.Nature genetics · 2026Article
- Glucose-induced histone lactylation confers metformin resistance in colorectal cancer stem cells.Nature communications · 2026Article
- Phenformin-Induced Apoptosis: A Potential Mechanism for Cervical Cancer Cell Inhibition.International journal of molecular sciences · 2026Article
- The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026Review
- Metformin Renders Survival Advantage to Patients with Glioblastoma Multiforme.Neurology international · 2026Review
- The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor.Journal of translational medicine · 2026Review
- Heterogeneity of glucose metabolism and uptake identifies distinct cancer cell and cancer stem cell phenotypes.Cellular & molecular biology letters · 2026Article
- Hydrophilic metformin and hydrophobic biguanides inhibit mitochondrial complex I by distinct mechanisms.Nature structural & molecular biology · 2026Article
- Re/Journal of medicinal chemistry · 2025Article
- Dysregulation of Mitochondrial Function in Cancer Cells.International journal of molecular sciences · 2025Review
- Metformin reverses 5-FU resistance induced by radiotherapy through mediating folate metabolism in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- An update on cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer.Future oncology (London, England) · 2025Review
- Biguanides antithetically regulate tumor properties by the dose-dependent mitochondrial reprogramming-driven c-Src pathway.Cell reports. Medicine · 2025Article
- BET inhibitors (BETi) influence oxidative phosphorylation metabolism by affecting mitochondrial dynamics leading to alterations in apoptotic pathways in triple-negative breast cancer (TNBC) cells.Cell proliferation · 2024Article
- Anti-echinococcal effect of metformin in advanced experimental cystic echinococcosis: reprogrammed intermediary carbon metabolism in the parasite.Antimicrobial agents and chemotherapy · 2024Article
- Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration.Biology open · 2024Review
- Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK.International journal of oral science · 2024Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
120 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Metformin, a first-line diabetes drug linked to cancer prevention in retrospective clinical analyses, inhibits cellular transformation and selectively kills breast cancer stem cells (CSCs). Although a few metabolic effects of metformin and the related biguanide phenformin have been investigated in established cancer cell lines, the global metabolic impact of biguanides during the process of neoplastic transformation and in CSCs is unknown. Here, we use LC/MS/MS metabolomics (>200 metabolites) to assess metabolic changes induced by metformin and phenformin in an Src-inducible model of cellular transformation and in mammosphere-derived breast CSCs. Although phenformin is the more potent biguanide in both systems, the metabolic profiles of these drugs are remarkably similar, although not identical. During the process of cellular transformation, biguanide treatment prevents the boost in glycolytic intermediates at a specific stage of the pathway and coordinately decreases tricarboxylic acid (TCA) cycle intermediates. In contrast, in breast CSCs, biguanides have a modest effect on glycolytic and TCA cycle intermediates, but they strongly deplete nucleotide triphosphates and may impede nucleotide synthesis. These metabolic profiles are consistent with the idea that biguanides inhibit mitochondrial complex 1, but they indicate that their metabolic effects differ depending on the stage of cellular transformation.
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Registered trials
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