Metformin induces a senescence-associated gene signature in breast cancer cells
Open accessAbstract
Diabetic patients taking metformin have lower incidence of breast cancer than those taking other anti-diabetic medications. Additionally, triple negative breast cancer (TNBC), a form of breast cancer disproportionately afflicting premenopausal African American women, shows atypical susceptibility to metformin’s antiproliferative effect. The mechanisms involved in metformin’s function in TNBC has not yet been fully elucidated. Therefore, we sought to identify pathways regulated by metformin in using the MDA-MB-468 TNBC cell model. Metformin dose-dependently caused apoptosis, decreased cell viability, and induced cell morphology/chromatin condensation consistent with the permanent proliferative arrest. Furthermore, gene expression arrays revealed that metformin caused expression of stress markers DDIT3, CYP1A1,and GDF-15 and a concomitant reduction in PTGS1 expression. Our findings show that metformin may affect the viability and proliferative capacity of TNBC by inducing an antiproliferative gene signature, and that metformin may be effective in the treatment/prevention of TNBC.
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In breast cancer, low-dose metformin induces a SASP gene expression signature.
“However, in the context of breast cancer and hepatoma, low dose metformin has been previously shown to induce SASP gene expression signature and p53-dependent senescence, respectively (Williams et al. 2013, Yi et al. 2013).”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Williams et al. 2013
1 mM metformin upregulates GDF-15 gene expression in breast cancer cells to 26-fold compared with control.
“In vitro, 1mM of metformin upregulated GDF-15 gene expression in breast cancer cells to 26-fold compared with control (79).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [79]
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References 23 · Cited by 22
- Authors
- Williams, C. C., Singleton, B. A., Llopis, S. D., & Skripnikova, E. V.
- Affiliations
- Xavier University of Louisiana (US)
- Venue
- Journal of Health Care for the Poor and Underserved
- Publisher
- Project MUSE
- Published
- 2013-02
- Volume
- 24
- Issue
- 1A
- Pages
- 93-103
- ISSN
- 1049-2089 (ISSN-L)
- 1548-6869
- PMC
- PMC3680098
- OpenAlex
- W1983287840
- Cited by
- 22
- References
- 23
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Health Care for the Poor and Underserved (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Project Muse (Johns Hopkins University) (submittedVersion)
- Funders
- National Cancer Institute (K01CA129078)
- National Center for Research Resources (G12RR026260)
- National Institute on Minority Health and Health Disparities (G12MD007595)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- metformin, triple-negative breast cancer, cellular senescence, apoptosis, DDIT3, CYP1A1, GDF15, PTGS1, MDA-MB-468, diabetes and cancer risk, African American women
- MeSH terms
- Breast Neoplasms, Female, Humans, Metformin, Gene Expression Regulation, Neoplastic, Cellular Senescence, Cell Culture Techniques
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