Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro
Open accessAbstract
The anti-diabetic drug metformin reduces human cancer incidence and improves the survival of cancer patients, including those with breast cancer. We studied the activity of metformin against diverse molecular subtypes of breast cancer cell lines in vitro. Metformin showed biological activity against all estrogen receptor (ER) positive and negative, erbB2 normal and abnormal breast cancer cell lines tested. It inhibited cellular proliferation, reduced colony formation and caused partial cell cycle arrest at the G(1) checkpoint. Metformin did not induce apoptosis (as measured by DNA fragmentation and PARP cleavage) in luminal A, B or erbB2 subtype breast cancer cell lines. At the molecular level, metformin treatment was associated with a reduction of cyclin D1 and E2F1 expression with no changes in p27(kip1) or p21(waf1). It inhibited mitogen activated protein kinase (MAPK) and Akt activity, as well as the mammalian target of rapamycin (mTOR) in both ER positive and negative, erbB2-overexpressing and erbB2-normal expressing breast cancer cells. In erbB2-overexpressing breast cancer cell lines, metformin reduced erbB2 expression at higher concentrations, and at lower concentrations within the therapeutic range, it inhibited erbB2 tyrosine kinase activity evidenced by a reduction of phosphorylated erbB2 (P-erbB2) at both auto- and Src- phosphorylation sites. These data suggest that metformin may have potential therapeutic utility against ER positive and negative, erbB2-overexpressing and erbB2-normal expressing breast cancer cells.
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In laboratory studies, metformin inhibits cell proliferation, reduces colony formation, and causes partial cell cycle arrest in cancer cell lines.
“In laboratory studies, metformin has been shown to inhibit cell proliferation, reduce colony formation, and cause partial cell cycle arrest in cancer cell lines (81–83).”
From Diabetes and Cancer (2010) · cites this paper as [82]
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- Authors
- Alimova, I. N., Liu, B., Fan, Z., Edgerton, S. M., Dillon, T., Lind, S. E., & Thor, A. D.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Thor, Ann D.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2009-03-15
- Volume
- 8
- Issue
- 6
- Pages
- 909-915
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W1990063646
- Cited by
- 523
- References
- 40
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 16 · 2023: 23 · 2022: 25 · 2021: 28 · 2020: 33 · 2019: 28 · 2018: 36 · 2017: 35 · 2016: 39 · 2015: 41 · 2014: 39 · 2013: 34 · 2012: 32
- FWCI
- 15.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Avon Foundation for Women
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- metformin, breast cancer, cell cycle arrest, G1/S checkpoint, colony formation, cell proliferation, estrogen receptor, HER2 overexpression, MAPK signaling, Akt signaling, mTOR, cyclin D1, E2F1, p27, p21, anticancer drug repurposing, tyrosine kinase inhibition
- MeSH terms
- Breast Neoplasms, Cell Cycle, Humans, Hypoglycemic Agents, Metformin, Receptors, Estrogen, Signal Transduction, Apoptosis, Erb-b2 Receptor Tyrosine Kinases, Cell Line, Tumor, Cell Proliferation
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