ArticleEndocrine-related cancer2015
Glucose-deprivation increases thyroid cancer cells sensitivity to metformin.
Article in Endocrine-related cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Biological Anti-Tumoral Mechanisms of Metformin in Head and Neck Squamous Cell Carcinomas: A Systematic Review.Journal of clinical medicine · 2025Review
- Metabolic Reprogramming in Thyroid Cancer.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Effect of metformin alone and in combination with etoposide and epirubicin on proliferation, apoptosis, necrosis, and migration of B-CPAP and SW cells as thyroid cancer cell lines.Research in pharmaceutical sciences · 2023Article
- Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs.Frontiers in pharmacology · 2023Review
- Reprogramming of Cellular Metabolism and Its Therapeutic Applications in Thyroid Cancer.Metabolites · 2022Review
- Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy.Medicina (Kaunas, Lithuania) · 2022Review
- Metformin in Differentiated Thyroid Cancer: Molecular Pathways and Its Clinical Implications.Biomolecules · 2022Review
- Article
- Metformin Intervention-A Panacea for Cancer Treatment?Cancers · 2022Review
- Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models.Biomolecules · 2022Review
- Cytochrome C Oxidase Subunit 4 (COX4): A Potential Therapeutic Target for the Treatment of Medullary Thyroid Cancer.Cancers · 2020Article
- Low glucose enhanced metformin's inhibitory effect on pancreatic cancer cells by suppressing glycolysis and inducing energy stress via up-regulation of miR-210-5p.Cell cycle (Georgetown, Tex.) · 2020Article
- AMPK activation overcomes anti-EGFR antibody resistance induced by KRAS mutation in colorectal cancer.Cell communication and signaling : CCS · 2020Article
- Review
- Anticancer activity of metformin: a systematic review of the literature.Future science OA · 2019Review
- Metabolic reprogramming and its clinical application in thyroid cancer.Oncology letters · 2019Review
- Heme Oxygenase-1 Inhibition Sensitizes Human Prostate Cancer Cells towards Glucose Deprivation and Metformin-Mediated Cell Death.International journal of molecular sciences · 2019Article
- Role of global aberrant alternative splicing events in papillary thyroid cancer prognosis.Aging · 2019Article
- Low-dose 2-deoxyglucose and metformin synergically inhibit proliferation of human polycystic kidney cells by modulating glucose metabolism.Cell death discovery · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Metformin inhibits thyroid cancer cell growth. We sought to determine if variable glucose concentrations in medium alter the anti-cancer efficacy of metformin. Thyroid cancer cells (FTC133 and BCPAP) were cultured in high-glucose (20 mM) and low-glucose (5 mM) medium before treatment with metformin. Cell viability and apoptosis assays were performed. Expression of glycolytic genes was examined by real-time PCR, western blot, and immunostaining. Metformin inhibited cellular proliferation in high-glucose medium and induced cell death in low-glucose medium. In low-, but not in high-glucose medium, metformin induced endoplasmic reticulum stress, autophagy, and oncosis. At micromolar concentrations, metformin induced phosphorylation of AMP-activated protein kinase and blocked p-pS6 in low-glucose medium. Metformin increased the rate of glucose consumption from the medium and prompted medium acidification. Medium supplementation with glucose reversed metformin-inducible morphological changes. Treatment with an inhibitor of glycolysis (2-deoxy-d-glucose (2-DG)) increased thyroid cancer cell sensitivity to metformin. The combination of 2-DG with metformin led to cell death. Thyroid cancer cell lines were characterized by over-expression of glycolytic genes, and metformin decreased the protein level of pyruvate kinase muscle 2 (PKM2). PKM2 expression was detected in recurrent thyroid cancer tissue samples. In conclusion, we have demonstrated that the glucose concentration in the cellular milieu is a factor modulating metformin's anti-cancer activity. These data suggest that the combination of metformin with inhibitors of glycolysis could represent a new strategy for the treatment of thyroid cancer.
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