ArticleCells2019
Metformin Impairs Glutamine Metabolism and Autophagy in Tumour Cells.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Metformin Treatment Potentially Modifies Genetically Driven Metabolite-HbA1c Associations: A Gene-Environment Interaction Mendelian Randomization Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin.The Eurasian journal of medicine · 2026Article
- Metabolic reprogramming networks in the gastric cancer tumor microenvironment: an integrated axis of nutrient competition, metabolic crosstalk, and immunosuppression.Frontiers in immunology · 2026Review
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- Article
- Drug Repurposing: A Conduit to Unravelling Metabolic Reprogramming for Cancer Treatment.Mini reviews in medicinal chemistry · 2025Review
- Metabolomic Profiling of Oral Potentially Malignant Disorders and Its Clinical Values.Biomedicines · 2024Review
- A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases.Molecular and cellular biochemistry · 2024Review
- Pharmacometabolomic Approach to Investigate the Response to Metformin in Patients with Type 2 Diabetes: A Cross-Sectional Study.Biomedicines · 2023Article
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- The Role and Mechanism of Metformin in Inflammatory Diseases.Journal of inflammation research · 2023Review
- Effect of Metformin on the Prognosis of Gastric Cancer Patients with Type 2 Diabetes Mellitus: A Meta-Analysis Based on Retrospective Cohort Studies.International journal of endocrinology · 2023Article
- Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice.International journal of molecular sciences · 2022Article
- Metformin Treatment Induces Different Response in Pheochromocytoma/Paraganglioma Tumour Cells and in Primary Fibroblasts.Cancers · 2022Article
- Review
- Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions.International journal of molecular sciences · 2022Article
- Review
- 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
- GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy.Theranostics · 2021Article
- Repurposing of metformin and colchicine reveals differential modulation of acute and chronic kidney injury.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin has been shown to inhibit glutaminase (GLS) activity and ammonia accumulation thereby reducing the risk of hepatic encephalopathy in type 2 diabetic patients. Since tumour cells are addicted to glutamine and often show an overexpression of glutaminase, we hypothesize that the antitumoral mechanism of metformin could be ascribed to inhibition of GLS and reduction of ammonia and ammonia-induced autophagy. Our results show that, in different tumour cell lines, micromolar doses of metformin prevent cell growth by reducing glutamate, ammonia accumulation, autophagy markers such as MAP1LC3B-II and GABARAP as well as degradation of long-lived proteins. Reduced autophagy is then accompanied by increased BECN1/BCL2 binding and apoptotic cell death. Interestingly, GLS-silenced cells reproduce the effect of metformin treatment showing reduced MAP1LC3B-II and GABARAP as well as ammonia accumulation. Since metformin is used as adjuvant drug to increase the efficacy of Cisplatin-based neoadjuvant chemotherapy, we co-treated tumour cells with micromolar doses of metformin in the presence of cisplatin observing a marked reduction of MAP1LC3B-II and an increase of caspase 3 cleavage. In conclusion, our work demonstrates that the anti-tumoral action of metformin is due to the inhibition of glutaminase and autophagy and could be used to improve the efficacy of chemotherapy.
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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.