ArticleJournal of biomedical science2018
Metformin causes cancer cell death through downregulation of p53-dependent differentiated embryo chondrocyte 1.
Article in Journal of biomedical science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Pleiotropic Effects of Metformin on the Chemotherapy Response of HPV-Positive Cancer Cells.Journal of medical virology · 2025Article
- Metformin exerted tumoricidal effects on colon cancer tumoroids via the regulation of autophagy pathway.Stem cell research & therapy · 2025Article
- Current insights and future directions of Li-Fraumeni syndrome.Discover oncology · 2024Review
- Factors affecting the expression and stability of full-length and truncated SRSF3 proteins in human cancer cells.Scientific reports · 2024Article
- [Procine recombinant NK-lysin inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 and inhibiting oxidative phosphorylation and glycolysis: a proteomic analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Characteristics of the Cytotoxicity ofInternational journal of molecular sciences · 2022Article
- Obesity and Breast Cancer Risk: The Oncogenic Implications of Metabolic Dysregulation.The Journal of clinical endocrinology and metabolism · 2022Article
- Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions.Aging and disease · 2022Article
- Review
- Review
- Metformin Potentiates the Anticancer Effect of Everolimus on Cervical Cancer In Vitro and In Vivo.Cancers · 2021Article
- Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells.Scientific reports · 2021Article
- Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Review
- Differential Cytotoxicity Mechanisms of Copper Complexed with Disulfiram in Oral Cancer Cells.International journal of molecular sciences · 2021Article
- Mechanisms of Cisplatin in Combination with Repurposed Drugs against Human Endometrial Carcinoma Cells.Life (Basel, Switzerland) · 2021Article
- The Effects of NT-1044, a Novel AMPK Activator, on Endometrial Cancer Cell Proliferation, Apoptosis, Cell Stress andFrontiers in oncology · 2021Article
- Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells.Molecular medicine reports · 2021Article
- Mechanisms and Applications of the Anti-cancer Effect of Pharmacological Ascorbic Acid in Cervical Cancer Cells.Frontiers in oncology · 2020Article
- Metformin: A Possible Option in Cancer Chemotherapy.Analytical cellular pathology (Amsterdam) · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMetformin is the most commonly used first-line medicine for type II diabetes mellitus. Acting via AMP-activated protein kinase, it has been used for more than 60 years and has an outstanding safety record. Metformin also offers protection against cancer, but its precise mechanisms remain unclear.
methodsWe first examined the cytotoxic effects of metformin in the HeLa human cervical carcinoma and ZR-75-1 breast cancer cell lines using assays of cell viability, cleaved poly-ADP-ribose polymerase, and Annexin V-fluorescein isothiocyanate apoptosis, as well as flow cytometric analyses of the cell cycle profile and reactive oxygen species (ROS). We later clarified the effect of metformin on p53 protein stability using transient transfection and cycloheximide chase analyses.
resultsWe observed that metformin represses cell cycle progression, thereby inducing subG1 populations, and had induced apoptosis through downregulation of p53 protein and a target gene, differentiated embryo chondrocyte 1 (DEC1). In addition, metformin increased intracellular ROS levels, but N-acetyl cysteine, a ROS scavenger, failed to suppress metformin-induced apoptosis. Further results showed that metformin disrupted the electron transport chain and collapsed the mitochondrial membrane potential, which may be the cause of the elevated ROS levels. Examination of the mechanisms underlying metformin-induced HeLa cell death revealed that reduced stability of p53 in metformin-treated cells leads to decreases in DEC1 and induction of apoptosis.
conclusionThe involvement of DEC1 provides new insight into the positive or negative functional roles of p53 in the metformin-induced cytotoxicity in tumor cells.
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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.