ArticleAging2012
Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs.
Article in Aging, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 119 citations in OpenAlex.
- Trial
- Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study.PloS one · 2022Trial
- Trial
- Metformin reverses 5-FU resistance induced by radiotherapy through mediating folate metabolism in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.International journal of molecular sciences · 2024Review
- 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
- Metformin as a PotentialInternational journal of breast cancer · 2024Review
- Serum Concentrations and Dietary Intake of Vitamin BInternational journal of molecular sciences · 2023Article
- Downregulation of phosphoserine phosphatase potentiates tumor immune environments to enhance immune checkpoint blockade therapy.Journal for immunotherapy of cancer · 2023Article
- Role of MOTS-c in the regulation of bone metabolism.Frontiers in physiology · 2023Review
- Divergent Metabolic Effects of Metformin Merge to Enhance Eicosapentaenoic Acid Metabolism and Inhibit Ovarian Cancer In Vivo.Cancers · 2022Article
- Article
- Effects of Metformin Combined With Antifolates on HepG2 Cell Metabolism and Cellular Proliferation.Frontiers in oncology · 2022Article
- Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells.Scientific reports · 2021Article
- Article
- Review
- Interaction between Metformin, Folate and Vitamin BInternational journal of molecular sciences · 2021Review
- Metformin - its anti-cancer effects in hematologic malignancies.Oncology reviews · 2021Article
- Metformin and Malignant Tumors: Not Over the Hill.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Tumor Cell-Intrinsic Immunometabolism and Precision Nutrition in Cancer Immunotherapy.Cancers · 2020Article
21 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
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolomic fingerprint of breast cancer cells treated with the antidiabetic drug metformin revealed a significant accumulation of 5-formimino-tetrahydrofolate, one of the tetrahydrofolate forms carrying activated one-carbon units that are essential for the de novo synthesis of purines and pyrimidines. De novo synthesis of glutathione, a folate-dependent pathway interconnected with one-carbon metabolism was concomitantly depleted in response to metformin. End-product reversal studies demonstrated that thymidine alone leads to a significant but incomplete protection from metformin's cytostatic effects. The addition of the substrate hypoxanthine for the purine salvage pathway produces major rightward shifts in metformin's growth inhibition curves. Metformin treatment failed to activate the DNA repair protein ATM kinase and the metabolic tumor suppressor AMPK when thymidine and hypoxanthine were present in the extracellular milieu. Our current findings suggest for the first time that metformin can function as an antifolate chemotherapeutic agent that induces the ATM/AMPK tumor suppressor axis secondarily following the alteration of the carbon flow through the folate-related one-carbon metabolic pathways.
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What OpenQuestion holds
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.