Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission
Open accessAbstract
The cancer stem cell hypothesis suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectively target cancer stem cells offer great promise for cancer treatment, particularly in combination with chemotherapy. Here, we show that low doses of metformin, a standard drug for diabetes, inhibits cellular transformation and selectively kills cancer stem cells in four genetically different types of breast cancer. The combination of metformin and a well-defined chemotherapeutic agent, doxorubicin, kills both cancer stem cells and non–stem cancer cells in culture. Furthermore, this combinatorial therapy reduces tumor mass and prevents relapse much more effectively than either drug alone in a xenograft mouse model. Mice seem to remain tumor-free for at least 2 months after combinatorial therapy with metformin and doxorubicin is ended. These results provide further evidence supporting the cancer stem cell hypothesis, and they provide a rationale and experimental basis for using the combination of metformin and chemotherapeutic drugs to improve treatment of patients with breast (and possibly other) cancers. [Cancer Res 2009;69(19):7507–11]
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The association of metformin and doxorubicin killed both cancer stem cells and non-stem cancer cells in culture.
“The association of metformin and doxorubicin killed both cancer stem cells and non-stem cancer cells in culture.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [157]
The association of metformin and doxorubicin may reduce tumor mass and prevent relapse more effectively than either drug used as monotherapy.
“This may reduce tumor mass and prevent relapse more effectively than either drug used as monotherapy [157].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [157]
Low doses of metformin inhibited cellular transformation and selectively killed cancer stem cells in four genetically different types of breast cancer in a mouse xenograft model.
“Low doses of metformin inhibited cellular transformation and selectively killed cancer stem cells in four genetically different types of breast cancer in a mouse xenograft model.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [157]
Metformin may selectively kill cancer stem cells and enhance effectiveness of breast cancer treatment regimens.
“Other in vitro studies suggest that metformin may selectively kill cancer stem cells and enhance effectiveness of breast cancer treatment regimens (85–87).”
From Diabetes and Cancer (2010) · cites this paper as [86]
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- Authors
- Hirsch, H. A., Iliopoulos, D., Tsichlis, P. N., & Struhl, K.
- Affiliations
- Harvard University (US)
- Tufts Medical Center (US)
- Corresponding author
- Struhl, Kevin
- Venue
- Cancer Research
- Published
- 2009-10-01
- Volume
- 69
- Issue
- 19
- Pages
- 7507-7511
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2756324
- OpenAlex
- W2125747634
- Cited by
- 1,115
- References
- 18
- Citations by year
- 2026: 26 · 2025: 24 · 2024: 25 · 2023: 48 · 2022: 40 · 2021: 54 · 2020: 52 · 2019: 81 · 2018: 66 · 2017: 89 · 2016: 79 · 2015: 101 · 2014: 107 · 2013: 91 · 2012: 86
- FWCI
- 31.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Cancer Society
- National Institutes of Health
- National Cancer Institute (CA 57436, R01CA107486, CA107486, R01CA057436)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- metformin, cancer stem cells, breast cancer, doxorubicin, combination chemotherapy, cancer stem cell hypothesis, tumor recurrence, tumor xenografts, drug repurposing, cell transformation
- MeSH terms
- Adult, Animals, Antineoplastic Combined Chemotherapy Protocols, Breast, Breast Neoplasms, Cell Transformation, Neoplastic, Doxorubicin, Female, Humans, Metformin, Mice, Nude, Random Allocation, Neoplastic Stem Cells, Xenograft Model Antitumor Assays, Cell Line, Tumor, Cell Growth Processes, Mice
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