ArticleMetabolites2021
Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation.
Article in Metabolites, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- Umbilical cord-derived mitochondrial transplantation restores tendon structure and function in a preclinical model of achilles tendinopathy.Journal of translational medicine · 2026Article
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- Nine-Year Recurrence-Free Survival in Gastric Signet-Ring Cell Carcinoma: A Case Report of Laparoscopic Radical Resection Combining Long-Term Systematic Therapy and Metformin Enteric-Coated Tablets.Case reports in medicine · 2026Article
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Multi-omics based and AI-driven drug repositioning for epigenetic therapy in female malignancies.Journal of translational medicine · 2025Review
- Bioinformatic Insights and XGBoost Identify Shared Genetics in Chronic Obstructive Pulmonary Disease and Type 2 Diabetes.The clinical respiratory journal · 2025Article
- Investigation of potential anti-metastatic effect of metformin and caffeic acid combination therapy in breast cancer cell line in in-vitro culture model.Medical oncology (Northwood, London, England) · 2025Article
- Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i.Cardiovascular diabetology · 2024Article
- Article
- The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors.Cellular & molecular biology letters · 2022Article
- Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Metabolomics and the Multi-Omics View of Cancer.Metabolites · 2022Review
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
The biguanide drug metformin has been widely used for the treatment of type 2 diabetes, and there is evidence supporting the anticancer effect of metformin despite some controversy. Here, we report the growth inhibitory activity of metformin in the breast cancer (MCF-7) cells, both in vitro and in vivo, and the associated metabolic changes. In particular, a decrease in a well-known oncometabolite 2-hydroxyglutarate (2-HG) was discovered by a metabolomics approach. The decrease in 2-HG by metformin was accompanied by the reduction in histone methylation, consistent with the known tumorigenic mechanism of 2-HG. The relevance of 2-HG inhibition in breast cancer was also supported by a higher level of 2-HG in human breast cancer tissues. Genetic knockdown of PHGDH identified the PHGDH pathway as the producer of 2-HG in the MCF-7 cells that do not carry isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) mutations, the conventional producer of 2-HG. We also showed that metformin's inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway. Overall, our results provide an explanation for the coherent pathway from complex I inhibition to epigenetic changes for metformin's anticancer effect.
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