ArticleExperimental and therapeutic medicine2016
Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells
Article in Experimental and therapeutic medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Paracetamol and Metformin Reduce NK-Cell Susceptibility in MCF-7 Breast Cancer Cells in Association with Enrichment of Immune-Evasive CD44International journal of molecular sciences · 2026Article
- Metformin Enhances 2-Aminoethyl Dihydrogen Phosphate-Induced Mitochondrial Dysfunction and Apoptosis in Melanoma Cells.International journal of molecular sciences · 2026Article
- Metformin-Induced Apoptosis Is Mediated Through Mitochondrial VDAC1.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Investigation of the synergistic effect of metformin and FX11 on PANC-1 cell lines.Biological research · 2025Article
- Effect of metformin on cell proliferation and apoptosis in steatosis HepG2 cell model.Northern clinics of Istanbul · 2025Article
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Article
- Metformin-induced oxidative stress inhibits LNCaP prostate cancer cell survival.Molecular biology reports · 2024Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study.Molecules (Basel, Switzerland) · 2024Article
- Demonstrating drug treatment efficacies by monitoring superoxide dynamics in human lung cancer cells with time-lapse fluorescence microscopy.Journal of biophotonics · 2024Article
- Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.Cancer biology & therapy · 2023Article
- Metformin and Aspirin: Anticancer effects on A549 and PC3 cancer cells and the mechanisms of action.Toxicology research · 2023Article
- Metformin and Cervical Cancer Risk in Patients with Newly Diagnosed Type 2 Diabetes: A Population-Based Study in Korea.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Combined treatment with glucagon-like peptide-1 receptor agonist exendin-4 and metformin attenuates breast cancer growth.Diabetology international · 2022Article
- Microarray analysis of breast cancer gene expression profiling in response to 2-deoxyglucose, metformin, and glucose starvation.Cancer cell international · 2022Article
- The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC.International journal of molecular sciences · 2022Article
- In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis.Saudi journal of biological sciences · 2021Article
- The role of AMPK/mTOR signaling pathway in anticancer activity of metformin.Physiological research · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is the most commonly occurring cancer and second leading cause of mortality in women. Metformin is a widely prescribed anti-hyperglycemic drug, which is emerging as a potential cancer preventative and treatment agent. However, the mechanisms underlying the suppressive effects of metformin on cancer cell growth and the induction of cancer cell apoptosis are not fully elucidated. The present study aimed to identify the pathways regulated by metformin in two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Cells were treated with various concentrations of metformin and then evaluated with respect to viability, proliferation, adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels, mitochondrial membrane potential (∆ψm), and the expression of anti- and pro-apoptotic proteins. Metformin caused apoptosis in a concentration- and time-dependent manner, and decreased cell viability and ATP production. Furthermore, metformin induced the generation of ROS and decreased the ∆ψm. Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. These results demonstrate that the apoptotic and cytotoxic effects of metformin on breast cancer cells are mediated by the intrinsic mitochondria-mediated apoptosis pathway.
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