Phenformin as prophylaxis and therapy in breast cancer xenografts
Open accessAbstract
BACKGROUND: Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231. METHODS: Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis. RESULTS: Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation. CONCLUSION: Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer.
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Other complex I inhibitors have shown efficacy as anti-tumor agents and may show selective toxicity against oncogene-ablation resistant cells and cancer stem cells.
“Consistent with this notion, other complex I inhibitors have shown efficacy as anti-tumor agents (Appleyard et al., 2012; Schockel et al., 2015) and may show selective toxicity against oncogene-ablation resistant cells (Viale et al., 2014) and cancer stem cells (Sancho et al., 2015).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Appleyard et al., 2012
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Targeting Metabolism for Cancer Therapy
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- Authors
- Appleyard, M. V. C. L., Murray, K. E., Coates, P. J., Wullschleger, S., Bray, S. E., Kernohan, N. M., Fleming, S., Alessi, D. R., & Thompson, A. M.
- Affiliations
- University of Dundee (GB)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Appleyard, M V C L
- Venue
- British Journal of Cancer
- Published
- 2012-02-23
- Volume
- 106
- Issue
- 6
- Pages
- 1117-1122
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3304424
- OpenAlex
- W1977613875
- Cited by
- 108
- References
- 45
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 9 · 2022: 5 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 12 · 2014: 10 · 2013: 13 · 2012: 6
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- 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
- phenformin, metformin, biguanides, breast cancer, chemoprophylaxis, estrogen receptor-positive breast cancer, triple-negative breast cancer, MCF-7 xenografts, AMPK activation, anticancer agents, tumor growth inhibition, mitotic figures
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Adenylate Kinase, Animals, Antineoplastic Agents, Breast Neoplasms, Enzyme Activation, Female, Histones, Humans, Liver, Metformin, Mice, Nude, Phenformin, Poly(ADP-ribose) Polymerases, Spleen, Anticarcinogenic Agents, Ki-67 Antigen, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Mice
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