ArticleCell cycle (Georgetown, Tex.)2013
Mitochondrial dysfunction in breast cancer cells prevents tumor growth: understanding chemoprevention with metformin.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 86 citations in OpenAlex.
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- Dysregulation of Mitochondrial Function in Cancer Cells.International journal of molecular sciences · 2025Review
- Role of Innate Immunity in Cancer.Advances in experimental medicine and biology · 2025Review
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer.Journal of translational medicine · 2023Review
- Changes in the mammary gland during aging and its links with breast diseases.Acta biochimica et biophysica Sinica · 2023Review
- The role of cancer-associated fibroblasts in breast cancer metastasis.Frontiers in oncology · 2023Review
- Targeting of the tumor immune microenvironment by metformin.Journal of cell communication and signaling · 2022Review
- Identification of a prognostic signature in colorectal cancer using combinatorial algorithm-driven analysis.The journal of pathology. Clinical research · 2022Article
- Article
- Advances in metformin‑based metabolic therapy for non‑small cell lung cancer (Review).Oncology reports · 2022Review
- Lipid Metabolism Interplay in CRC-An Update.Metabolites · 2022Review
- Caffeic Acid Phenethyl Ester as a DHODH Inhibitor and Its Synergistic Anticancer Properties in Combination with 5-Fluorouracil in a Breast Cancer Cell Line.Journal of experimental pharmacology · 2022Article
- Overview of the molecular mechanisms contributing to the formation of cancer‑associated adipocytes (Review).Molecular medicine reports · 2021Review
- Breast cancer growth and proliferation is suppressed by the mitochondrial targeted furazano[3,4-b]pyrazine BAM15.Cancer & metabolism · 2021Article
- Article
- Molecular insights into the interplay between adiposity, breast cancer and bone metastasis.Clinical & experimental metastasis · 2021Review
- Crosstalk of the Caspase Family and Mammalian Target of Rapamycin Signaling.International journal of molecular sciences · 2021Review
- Cancer-associated adipocytes as immunomodulators in cancer.Biomarker research · 2021Review
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10 authors at 5 institutions in 4 countries.
Funding
Abstract
Metformin is a well-established diabetes drug that prevents the onset of most types of human cancers in diabetic patients, especially by targeting cancer stem cells. Metformin exerts its protective effects by functioning as a weak "mitochondrial poison," as it acts as a complex I inhibitor and prevents oxidative mitochondrial metabolism (OXPHOS). Thus, mitochondrial metabolism must play an essential role in promoting tumor growth. To determine the functional role of "mitochondrial health" in breast cancer pathogenesis, here we used mitochondrial uncoupling proteins (UCPs) to genetically induce mitochondrial dysfunction in either human breast cancer cells (MDA-MB-231) or cancer-associated fibroblasts (hTERT-BJ1 cells). Our results directly show that all three UCP family members (UCP-1/2/3) induce autophagy and mitochondrial dysfunction in human breast cancer cells, which results in significant reductions in tumor growth. Conversely, induction of mitochondrial dysfunction in cancer-associated fibroblasts has just the opposite effect. More specifically, overexpression of UCP-1 in stromal fibroblasts increases β-oxidation, ketone body production and the release of ATP-rich vesicles, which "fuels" tumor growth by providing high-energy nutrients in a paracrine fashion to epithelial cancer cells. Hence, the effects of mitochondrial dysfunction are truly compartment-specific. Thus, we conclude that the beneficial anticancer effects of mitochondrial inhibitors (such as metformin) may be attributed to the induction of mitochondrial dysfunction in the epithelial cancer cell compartment. Our studies identify cancer cell mitochondria as a clear target for drug discovery and for novel therapeutic interventions.
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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.