ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing.NPJ breast cancer · 2025Article
- Radiosensitizing Effects of Metformin on Ionizing Irradiation: An Overview of Animal and Clinical Studies.Current drug research reviews · 2025Review
- STAT3 Regulates the Redox Profile in MDA-MB-231 Breast Cancer Cells.Cell biochemistry and biophysics · 2024Article
- Metformin is a metabolic modulator and radiosensitiser in rectal cancer.Frontiers in oncology · 2023Article
- Microarray analysis of breast cancer gene expression profiling in response to 2-deoxyglucose, metformin, and glucose starvation.Cancer cell international · 2022Article
- Rosmanol induces breast cancer cells apoptosis by regulating PI3K/AKT and STAT3/JAK2 signaling pathways.Oncology letters · 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
- Biphasic effect of metformin on human cardiac energetics.Translational research : the journal of laboratory and clinical medicine · 2021Article
- Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.Nutrients · 2020Review
- Article
- Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer.Pharmaceutics · 2019Article
- Metformin and Breast Cancer: Molecular Targets.Journal of mammary gland biology and neoplasia · 2019Review
- Metformin Reshapes the Methylation Profile in Breast and Colorectal Cancer CellsAsian Pacific journal of cancer prevention : APJCP · 2018Article
- Dual Functional LipoMET Mediates Envelope-type Nanoparticles to Combinational Oncogene Silencing and Tumor Growth Inhibition.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Identification of novel dysregulated key genes in Breast cancer through high throughput ChIP-Seq data analysis.Scientific reports · 2017Article
- Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis.Therapeutic advances in medical oncology · 2017Article
- Differences in the starvation-induced autophagy response in MDA-MB-231 and MCF-7 breast cancer cells.Animal cells and systems · 2017Article
- NT1014, a novel biguanide, inhibits ovarian cancer growth in vitro and in vivo.Journal of hematology & oncology · 2016Article
- Metformin and AICAR regulate NANOG expression via the JNK pathway in HepG2 cells independently of AMPK.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.PloS one · 2016Article
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Authors and funding
13 authors.
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Abstract
The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 μM) and experimental concentrations of metformin (1000 and 5000 μM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor β1 (TGF-β1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-β1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer.
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