ArticlePLoS biology2015
Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis.
Article in PLoS biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
142 citing papers in PubMed, 212 citations in OpenAlex.
- Combination of metformin and double antibiotic paste for the regeneration of non-vital immature teeth: a preliminary randomized clinical study.BMC oral health · 2023Trial
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Dual Metabolic Targeting of Cancer: Lessons from Metformin and 2-Deoxy-D-Glucose Combinations.Cancers · 2026Article
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- AMPK-activated BAP1 regulates pVHL stability and tumor-suppressive functions.Cell death and differentiation · 2026Article
- Article
- Canagliflozin synergises with serine restriction mediating anti-leukaemic effects in T-cell acute lymphoblastic leukaemia.Molecular metabolism · 2025Article
- Repurposing Metformin in Precision Oncology: Mechanistic Insights, Biomarker-Guided Strategies, and Translational Imperatives.Medicina (Kaunas, Lithuania) · 2025Review
- Screening of patient-derived organoids identifies mitophagy as a cell-intrinsic vulnerability in colorectal cancer during statin treatment.Cell reports. Medicine · 2025Article
- Image-Based Measures of Obesity are Associated with Alterations in Metabolic Pathways in Non-small Cell Lung Cancer.Annals of surgical oncology · 2025Article
- DNA replication stress underpins the vulnerability to oxidative phosphorylation inhibition in colorectal cancer.Cell death & disease · 2025Article
- Reversal of metformin's anti-proliferative effect in fission yeastnpj metabolic health and disease · 2025Article
- Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.Frontiers in oncology · 2025Review
- Metformin Impairs Linsitinib Anti-Tumor Effect on Ovarian Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Metabolism of primary high-grade serous ovarian carcinoma (HGSOC) cells under limited glutamine or glucose availability.Cancer & metabolism · 2024Article
- Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i.Cardiovascular diabetology · 2024Article
- PoRVA G9P[23] and G5P[7] infections differentially promote PEDV replication by reprogramming glutamine metabolism.PLoS pathogens · 2024Article
- Article
- Identification of Fasnall as a therapeutically effective Complex I inhibitor.bioRxiv : the preprint server for biology · 2024Article
- Identification of glucose-independent and reversible metabolic pathways associated with anti-proliferative effect of metformin in liver cancer cells.Metabolomics : Official journal of the Metabolomic Society · 2024Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC). However, the mechanisms by which metformin arrests cancer cell proliferation remain poorly defined. Here we demonstrate that the metabolic checkpoint kinases AMP-activated protein kinase (AMPK) and LKB1 are not required for the antiproliferative effects of metformin. Rather, metformin inhibits cancer cell proliferation by suppressing mitochondrial-dependent biosynthetic activity. We show that in vitro metformin decreases the flow of glucose- and glutamine-derived metabolic intermediates into the Tricarboxylic Acid (TCA) cycle, leading to reduced citrate production and de novo lipid biosynthesis. Tumor cells lacking functional mitochondria maintain lipid biosynthesis in the presence of metformin via glutamine-dependent reductive carboxylation, and display reduced sensitivity to metformin-induced proliferative arrest. Our data indicate that metformin inhibits cancer cell proliferation by suppressing the production of mitochondrial-dependent metabolic intermediates required for cell growth, and that metabolic adaptations that bypass mitochondrial-dependent biosynthesis may provide a mechanism of tumor cell resistance to biguanide activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.