Cited by 1,048Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerCancer, Hypoxia, and Metabolism

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells

Open access

Zakikhani, Mahvash, Dowling, Ryan, Fantus, I. George, Sonenberg, Nahum, Pollak, Michael·2006·Cancer Research

Published version of a preprint

Open this paper in CoChat — free account Open PDF

Abstract

Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an "insulin sensitizer" because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with insulin resistance. As insulin and insulin-like growth factors stimulate proliferation of many normal and transformed cell types, agents that facilitate signaling through these receptors would be expected to enhance proliferation. We show here that metformin acts as a growth inhibitor rather than an insulin sensitizer for epithelial cells. Breast cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against AMP kinase. This shows that AMP kinase pathway activation by metformin, recently shown to be necessary for metformin inhibition of gluconeogenesis in hepatocytes, is also involved in metformin-induced growth inhibition of epithelial cells. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation. These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-06-1500

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950
The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797
A serine/threonine kinase gene defective in Peutz–Jeghers syndrome
Hemminki, A., Markie, D., Tomlinson, I. P. M., Avizienyte, E., Roth, S., Loukola, A., Bignell, G. R., Warren, W., Aminoff, M., Höglund, P., et al. (1998) · Nature · doi:10.1038/34432 · Cited by 1,680
Insulin-like growth factors and neoplasia
Pollak, M., Schernhammer, E. S., & Hankinson, S. E. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1387 · Cited by 1,477
Self-citation
Very high risk of cancer in familial Peutz–Jeghers syndrome
Giardiello, F. M., Brensinger, J. D., Tersmette, A. C., Goodman, S. N., Petersen, G. M., Booker, S. V., Cruz–Correa, M., & Offerhaus, G. J. A. (2000) · Gastroenterology · doi:10.1053/gast.2000.20228 · Cited by 1,435
The LKB1 tumor suppressor negatively regulates mTOR signaling
Shaw, R. J., Bardeesy, N. M., Manning, B. D., Lopez, L. V., Kosmatka, M., DePinho, R. A., & Cantley, L. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.007 · Cited by 1,107
Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study
Goodwin, P. J., Ennis, M., Pritchard, K. I., Trudeau, M. E., Koo, J., Madarnas, Y., Hartwick, W., Hoffman, B., & Hood, N. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.1.42 · Cited by 978

Show all 20 references

Sorted by citations

Items 501–600 of 1,000

Diabetes as a risk factor to cancer: Functional role of fermented papaya preparation as phytonutraceutical adjunct in the treatment of diabetes and cancer
Aruoma, O. I., Somanah, J., Bourdon, E., Rondeau, P., & Bahorun, T. (2014) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2014.04.007 · Cited by 38
Metformin and cancer: licence to heal?
Papanas, N., Maltezos, E., & Mikhailidis, D. P. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.499122 · Cited by 37
Novel epigallocatechin gallate analogs as potential anticancer agents: a patent review (2009 – present)
Landis‐Piwowar, K. R., Chen, D., Foldes, R. L., Chan, T. H., & Dou, Q. P. (2012) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2013.743993 · Cited by 37
Environmental Stress Affects the Activity of Metabolic and Growth Factor Signaling Networks and Induces Autophagy Markers in MCF7 Breast Cancer Cells
Casado, P., Bilanges, B., Rajeeve, V., Vanhaesebroeck, B., & Cutillas, P. R. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.034751 · Cited by 37
Effect of Metformin Use on Survival in Resectable Pancreatic Cancer: A Single-Institution Experience and Review of the Literature
Ambe, C. M., Mahipal, A., Fulp, J., Chen, L., & Malafa, M. P. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151632 · Cited by 39
Integrative miRNA analysis identifies hsa‐miR‐3154, hsa‐miR‐7‐3, and hsa‐miR‐600 as potential prognostic biomarker for cervical cancer
Zeng, Y., Wang, K., Xu, H., & Hong, Y. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26315 · Cited by 38
Metformin suppresses breast cancer growth via inhibition of cyclooxygenase‑2
Shi, B., Hu, X., He, H., & Fang, W. (2021) · Oncology Letters · doi:10.3892/ol.2021.12876 · Cited by 40
The Heterogeneity of Lipid Metabolism in Cancer
Park, J. K., Coffey, N. J., Limoges, A., & Le, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-65768-0_3 · Cited by 38
Thiolated alginate-based multiple layer mucoadhesive films of metformin forintra-pocket local delivery: in vitro characterization and clinical assessment
Kassem, A. A., Issa, D. A. E., Kotry, G. S., & Farid, R. M. (2016) · Drug Development and Industrial Pharmacy · doi:10.1080/03639045.2016.1224895 · Cited by 37
Targeting AMPK in the treatment of malignancies
Vakana, E., Altman, J. K., & Platanias, L. C. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23369 · Cited by 37
Diabetes and Its Link with Cancer: Providing the Fuel and Spark to Launch an Aggressive Growth Regime
Joshi, S., Liu, M., & Turner, N. A. (2015) · BioMed Research International · doi:10.1155/2015/390863 · Cited by 36
Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systematic review
Rêgo, D. F., Elias, S. T., Amato, A. A., Canto, G. D. L., & Guerra, E. N. S. (2016) · Oncology Letters · doi:10.3892/ol.2016.5526 · Cited by 37
Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial–mesenchymal transition in human colon cancer cells
Kang, S., Kim, B. R., Kang, M. H., Kim, D. Y., Lee, D.-H., Oh, S. C., Min, B. W., & Um, J. W. (2018) · PLoS ONE · doi:10.1371/journal.pone.0205449 · Cited by 36
Combination of Curcumin and Metformin Inhibits Cell Growth and Induces Apoptosis without Affecting the Cell Cycle in LNCaP Prostate Cancer Cell Line
Eslami, S. S., Jafari, D., Montazeri, H., Sadeghizadeh, M., & Tarighi, P. (2020) · Nutrition and Cancer · doi:10.1080/01635581.2020.1783327 · Cited by 36
The metformin in tuberous sclerosis (MiTS) study: A randomised double-blind placebo-controlled trial
Amin, S., Mallick, A. A., Edwards, H. B., Cortina‐Borja, M., Laugharne, M. J., Likeman, M. J., & O'Callaghan, F. J. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2020.100715 · Cited by 37
Co-delivery of Sildenafil (Viagra®) and Crizotinib for Synergistic and Improved Anti-tumoral Therapy
Marques, J. G., Gaspar, V. M., Oppolzer, D., Costa, E. C., Gallardo, E., & Correia, I. J. (2014) · Pharmaceutical Research · doi:10.1007/s11095-014-1347-x · Cited by 36
In Vitro and In Vivo Biological Evaluation of O-Carboxymethyl Chitosan Encapsulated Metformin Nanoparticles for Pancreatic Cancer Therapy
Snima, K. S., Jayakumar, R., & Lakshmanan, V. (2014) · Pharmaceutical Research · doi:10.1007/s11095-014-1425-0 · Cited by 37
Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk
Lauretta, R., Lanzolla, G., Vici, P., Mariani, L., Moretti, C., & Appetecchia, M. (2016) · International Journal of Endocrinology · doi:10.1155/2016/8671762 · Cited by 36
Dual Functional LipoMET Mediates Envelope-type Nanoparticles to Combinational Oncogene Silencing and Tumor Growth Inhibition
Shi, K., Zhao, Y. D., Miao, L., Satterlee, A., Haynes, M. T., Luo, C., Musetti, S., & Huang, L. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.02.008 · Cited by 36
Metformin turns 62 in pharmacotherapy: Emergence of non-glycaemic effects and potential novel therapeutic applications
Mbara, K. C., Mato, P. E. M., Driver, C., Nzuza, S., Mkhombo, N. T., Gcwensa, S. K., Mcobothi, E. N., & Owira, P. M. O. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.173934 · Cited by 36
Obesity and Cancer: Overview of Mechanisms
Nock, N. L., & Berger, N. A. (2010) · Springer eBooks · doi:10.1007/978-1-4419-5515-9_5 · Cited by 35
Energy Restriction for Breast Cancer Prevention
Howell, A., Chapman, M., & Harvie, M. (2008) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-540-69297-3_11 · Cited by 35
Differential expression of organic cation transporter OCT ‐3 in oral premalignant and malignant lesions: potential implications in the antineoplastic effects of metformin
Patel, H. Y., Younis, R. H., Ord, R. A., Basile, J. R., & Schneider, A. (2012) · Journal of Oral Pathology and Medicine · doi:10.1111/j.1600-0714.2012.01196.x · Cited by 35
The impact of metformin use on recurrence and cancer-specific survival in clinically localized high-risk renal cell carcinoma
Hakimi, A. A., Chen, L., Kim, P. H., Sjoberg, D. D., Glickman, L., Walker, M. R., & Russo, P. (2013) · Canadian Urological Association Journal · doi:10.5489/cuaj.1447 · Cited by 37
Targeting AMPK signaling in combating ovarian cancers: opportunities and challenges
Yung, M. M. H., Ngan, H., & Chan, D. W. (2016) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmv128 · Cited by 35
Metformin inhibits proliferation and growth hormone secretion of GH3 pituitary adenoma cells
An, J., Pei, X., Zang, Z., Zhou, Z. Y., Hu, J., Zheng, X., Zhang, Y., He, J., Duan, L., Shen, R., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16556 · Cited by 37
Alterations in Cellular Energy Metabolism Associated with the Antiproliferative Effects of the ATM Inhibitor KU-55933 and with Metformin
Zakikhani, M., Bazile, M., Hashemi, S., Javeshghani, S., Avizonis, D. Z., St‐Pierre, J., & Pollak, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049513 · Cited by 36
Self-citation
Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts
Lipner, M. B., Marayati, R., Deng, Y., Wang, X., Raftery, L., O’Neil, B. H., & Yeh, J. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147113 · Cited by 35
Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non–small cell lung cancer
Medairos, R. A., Clark, J., Holoubek, S. A., Kubasiak, J., Pithadia, R., Hamid, F., Chmielewski, G. W., Warren, W. H., Basu, S., Borgia, J. A., et al. (2016) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2016.03.094 · Cited by 34
A Retrospective Study on the Role of Diabetes and Metformin in Colorectal Cancer Disease Survival
Ramjeesingh, R., Orr, C., Bricks, C. S., Hopman, W. M., & Hammad, N. (2016) · Current Oncology · doi:10.3747/co.23.2809 · Cited by 34
Association of Metformin Use With Cancer-Specific Mortality in Hepatocellular Carcinoma After Curative Resection
Seo, Y.-S., Kim, Y.-J., Kim, M., Suh, K., Kim, S. B., Han, C. J., Kim, Y. J., Jang, W. I., Kang, S. H., Tchoe, H. J., et al. (2016) · Medicine · doi:10.1097/md.0000000000003527 · Cited by 34
Self-citation
AMP-activated protein kinase and energy balance in breast cancer.
Zhao, H., Orhan, Y. C., Zha, X., Esencan, E., Chatterton, R. T., & Bulun, S. E. (2017) · Europe PMC (PubMed Central) · Cited by 35
Repurposed Biguanide Drugs in Glioblastoma Exert Antiproliferative Effects via the Inhibition of Intracellular Chloride Channel 1 Activity
Barbieri, F., Verduci, I., Carlini, V., Zona, G., Pagano, A., Mazzanti, M., & Florio, T. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00135 · Cited by 34
The effect of metformin on biomarkers associated with breast cancer outcomes: a systematic review, meta-analysis, and dose–response of randomized clinical trials
Rahmani, J., Manzari, N., Thompson, J., Gudi, S. K., Chhabra, M., Naik, G., Mousavi, S. M., Varkaneh, H. K., Clark, C. C. T., & Zhang, Y. (2019) · Clinical & Translational Oncology · doi:10.1007/s12094-019-02108-9 · Cited by 34
The effect of metformin on the survival of colorectal cancer patients with type 2 diabetes mellitus
Tarhini, Z., Manceur, K., Magné, J., Mathonnet, M., Jost, J., & Christou, N. (2022) · Scientific Reports · doi:10.1038/s41598-022-16677-3 · Cited by 34
Exploring the Mechanism of Adjuvant Treatment of Glioblastoma Using Temozolomide and Metformin
Feng, S.-W., Chang, P.-C., Chen, H., Hueng, D., Li, Y., & Huang, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158171 · Cited by 36
Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1
Arnason, T., & Harkness, T. A. A. (2015) · Cancers · doi:10.3390/cancers7040877 · Cited by 33
Metformin Increases E-cadherin in Tumors of Diabetic Patients With Endometrial Cancer and Suppresses Epithelial-Mesenchymal Transition in Endometrial Cancer Cell Lines
Laskov, I., Abou-Nader, P., Amin, O., Philip, C., Beauchamp, M.-C., Yasmeen, A., & Gotlieb, W. H. (2016) · International Journal of Gynecological Cancer · doi:10.1097/igc.0000000000000761 · Cited by 34
Metformin suppresses gastric cancer progression through calmodulin‑like protein�3 secreted from tumor‑associated fibroblasts
Chen, G., Yu, C., Tang, Z., Liu, S., An, F., Zhu, J., Wu, Q., Cao, J., Zhan, Q., & Zhang, S. (2018) · Oncology Reports · doi:10.3892/or.2018.6783 · Cited by 34
The Interlinking Metabolic Association between Type 2 Diabetes Mellitus and Cancer: Molecular Mechanisms and Therapeutic Insights
Asiri, A., Qarni, A. A. A., & Bakillah, A. (2024) · Diagnostics · doi:10.3390/diagnostics14192132 · Cited by 37
Activation of AMP‐activated Protein Kinase and Phosphorylation of Glycogen Synthase Kinase3 β Mediate Ursolic Acid Induced Apoptosis in HepG2 Liver Cancer Cells
Son, H., Kwon, H. Y., Sohn, E. J., Lee, J., Woo, H.-J., Yun, M., Kim, S., & Kim, Y. (2013) · Phytotherapy Research · doi:10.1002/ptr.4925 · Cited by 34
Metformin does not improve survival in patients with hepatocellular carcinoma
Bhat, M. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i42.15750 · Cited by 33
Metformin and breast and gynecological cancer risk among women with diabetes
Soffer, D., Shi, J. M., Chung, J., Schottinger, J. E., Wallner, L. P., Chlebowski, R. T., Lentz, S. E., & Haque, R. (2015) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2014-000049 · Cited by 34
Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway
Huai, L., Wang, C., Zhang, C., Li, Q., Chen, Y., Jia, Y., Li, Y., Xing, H., Tian, Z., Rao, Q., et al. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.05.001 · Cited by 33
IGF1/insulin receptor kinase inhibition by BMS-536924 is better tolerated than alloxan-induced hypoinsulinemia and more effective than metformin in the treatment of experimental insulin-responsive breast cancer
Dool, C. J., Mashhedi, H., Zakikhani, M., David, S., Zhao, Y., Birman, E., Carboni, J. M., Gottardis, M. M., Blouin, M., & Pollak, M. (2011) · Endocrine Related Cancer · doi:10.1530/erc-11-0136 · Cited by 33
Self-citation
Effect of Advanced Glycation End Products on Lectin-Like Oxidized Low Density Lipoprotein Receptor-1 Expression in Endothelial Cells
Shiu, S. W. M., Wong, Y., & Tan, K. C. B. (2012) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.11742 · Cited by 33
Therapeutic Effects of Repurposed Therapies in Non-Small Cell Lung Cancer: What Is Old Is New Again
Saxena, A., Becker, D. J., Preeshagul, I. R., Lee, K. S., Katz, E., & Levy, B. P. (2015) · The Oncologist · doi:10.1634/theoncologist.2015-0064 · Cited by 34
Metformin and epithelial ovarian cancer therapeutics
Patel, S. V., Kumar, L., & Singh, N. (2015) · Cellular Oncology · doi:10.1007/s13402-015-0235-7 · Cited by 32
mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib
Hanly, E. K., Bednarczyk, R. B., Tuli, N. Y., Moscatello, A. L., Halicka, H. D., Li, J., Geliebter, J., Darżynkiewicz, Z., & Tiwari, R. K. (2015) · Oncotarget · doi:10.18632/oncotarget.4052 · Cited by 33
Metformin Inhibits Esophagus Cancer Proliferation through Upregulation of USP7
Xu, Y., & Lu, S. Y. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000354517 · Cited by 33
The Effect of Metformin and GANT61 Combinations on the Radiosensitivity of Prostate Cancer Cells
Gonnissen, A., Isebaert, S. F., McKee, C. M., Muschel, R. J., & Haustermans, K. M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020399 · Cited by 32
Combination of metformin and paclitaxel suppresses proliferation and induces apoptosis of human prostate cancer cells via oxidative stress and targeting the mitochondria‑dependent pathway
Zhao, Y., Zeng, X., Tang, H., Ye, D., & Liu, J. (2019) · Oncology Letters · doi:10.3892/ol.2019.10119 · Cited by 36
Metformin and 4SC‐202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma
He, Y., Tai, S., Deng, M., Fan, Z., Ping, F., He, L., Zhang, C., Huang, Y., Cheng, B., & Xia, J. (2019) · Cancer Medicine · doi:10.1002/cam4.2206 · Cited by 32
Effect of Aging on Homeostasis in the Soft Tissue of the Periodontium: A Narrative Review
Kim, Y. G., Lee, S. M., Bae, S., Park, T., Kim, H.-J., Jang, Y., Moon, K., Kim, H., Lee, K.-M., Park, J., et al. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11010058 · Cited by 35
Impact of Metformin on Male Reproduction
Ferreira, C., Sousa, M., Rabaça, A., Oliveira, P. F., Alves, M. G., & Sá, R. (2015) · Current Pharmaceutical Design · doi:10.2174/1381612821666150710150041 · Cited by 33
Mevalonate pathway inhibitors affect anticancer drug-induced cell death and DNA damage response of human sarcoma cells
Nilsson, S., Huelsenbeck, J., & Fritz, G. (2011) · Cancer Letters · doi:10.1016/j.canlet.2010.12.022 · Cited by 32
UCA1 involved in the metformin-regulated bladder cancer cell proliferation and glycolysis
Li, T., Sun, X.-Z., & Jiang, X. (2017) · Tumor Biology · doi:10.1177/1010428317710823 · Cited by 32
BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment
Andrieu, G. P., Shafran, J. S., Deeney, J. T., Bharadwaj, K. R., Rangarajan, A., & Denis, G. V. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.5ri0917-380rr · Cited by 33
No evidence for a decreased risk of thyroid cancer in association with use of metformin or other antidiabetic drugs: a case-control study
Becker, C., Jick, S. S., Meier, C. R., & Bodmer, M. (2015) · BMC Cancer · doi:10.1186/s12885-015-1719-6 · Cited by 32
Metformin inhibits growth and sensitizes osteosarcoma cell lines to cisplatin through cell cycle modulation
Quattrini, I., Conti, A., Pazzaglia, L., Novello, C., Ferrari, S. M., Picci, P., & Benassi, M. S. (2013) · Oncology Reports · doi:10.3892/or.2013.2862 · Cited by 31
Cancer Metabolism: Strategic Diversion from Targeting Cancer Drivers to Targeting Cancer Suppliers
Kim, S. (2015) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2015.013 · Cited by 31
Is it time to test biguanide metformin in the treatment of melanoma?
Cerezo, M., Tomić, T., Ballotti, R., & Rocchi, S. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12267 · Cited by 32
Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway
Liu, Y., ZHANG, Y., JIA, K., Dong, Y., & Ma, W. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2220 · Cited by 31
Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study
Mark, M. T., Klingbiel, D., Mey, U., Winterhalder, R., Rothermundt, C. A., Gillessen, S., von Moos, R., Pollak, M., Manetsch, G., Strebel, R. T., et al. (2019) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2018.12.009 · Cited by 31
Self-citation
Pharmacological Strategies for Insulin Sensitivity in Obesity and Cancer: Thiazolidinediones and Metformin
Biondo, L. A., Teixeira, A. A. S., Ferreira, K. C. D. O. S., & Neto, J. C. R. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200122124116 · Cited by 31
Case–control analysis on metformin and cancer of the esophagus
Becker, C., Meier, C. R., Jick, S. S., & Bodmer, M. (2013) · Cancer Causes & Control · doi:10.1007/s10552-013-0253-6 · Cited by 31
Metformin Induces Cell Cycle Arrest and Apoptosis in Drug-Resistant Leukemia Cells
Rodríguez-Lirio, A., Pérez‐Yarza, G., Fernández-Suárez, M. R., Alonso-Tejerina, E., Boyano, M. D., & Asumendi, A. (2015) · Leukemia Research and Treatment · doi:10.1155/2015/516460 · Cited by 31
High Glucose Accelerates Cell Proliferation and Increases the Secretion and mRNA Expression of Osteopontin in Human Pancreatic Duct Epithelial Cells
Ito, M., Makino, N., Matsuda, A., Ikeda, Y., Kakizaki, Y., Saito, Y., Ueno, Y., & Kawata, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040807 · Cited by 31
Metformin, B12, and Enhanced Breast Cancer Response to Chemotherapy
Garcia, A., & Tisman, G. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.7857 · Cited by 31
The Combination of Metformin and Valproic Acid Induces Synergistic Apoptosis in the Presence of p53 and Androgen Signaling in Prostate Cancer
Tran, L., Kichenadasse, G., Butler, L. M., Centenera, M. M., Morel, K. L., Ormsby, R. J., Michael, M., Lower, K. M., & Sykes, P. J. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0074 · Cited by 30
Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1α/PKM2 Signaling Pathway
Lei, R., Zhang, S., Wang, Y., Dai, S., Sun, J., & Zhu, C. (2019) · International Journal of Medical Sciences · doi:10.7150/ijms.32157 · Cited by 32
Metformin activates KDM2A to reduce rRNA transcription and cell proliferation by dual regulation of AMPK activity and intracellular succinate level
Tanaka, Y., Konishi, A., Obinata, H., & Tsuneoka, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-55075-0 · Cited by 31
Metformin and an insulin/IGF-1 receptor inhibitor are synergistic in blocking growth of triple-negative breast cancer
Xue, L., Chen, F., Yue, F., Camacho, L., Kothapalli, S., Wei, G., Huang, S., Mo, Q., Ma, F., Li, Y., et al. (2020) · Breast Cancer Research and Treatment · doi:10.1007/s10549-020-05927-5 · Cited by 33
WZB117 Decorated Metformin-Carboxymethyl Chitosan Nanoparticles for Targeting Breast Cancer Metabolism
De, A., Wadhwani, A. D., Sauraj, Roychowdhury, P., Kang, J. H., Ko, Y. T., & Kuppusamy, G. (2023) · Polymers · doi:10.3390/polym15040976 · Cited by 32
Effect of Metformin Use on Survival and Recurrence Rate of Gastric Cancer After Gastrectomy in Diabetic Patients: A Systematic Review and Meta-analysis of Observational Studies
Bahardoust, M., Mousavi, S., Moezi, Z. D., Yarali, M., Tayebi, A., Olamaeian, F., & Tizmaghz, A. (2023) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-023-00955-y · Cited by 30
DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells
Obara, A., Fujita, Y., Abulizi, A., Fukushima, T., Oguri, Y., Ogura, M., Harashima, S., Hosokawa, M., & Inagaki, N. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.03.148 · Cited by 31
Cisplatin Combined with Metformin Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Regulating E-cadherin and MMP-9
Sun, X., Zhang, P., Li, H.-H., Jiang, Z., Jiang, C., & Liu, H. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.9.4019 · Cited by 30
Amino acid profile in women with gestational diabetes mellitus treated with metformin or insulin
Huhtala, M. S., Tertti, K., Pellonperä, O., & Rönnemaa, T. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.09.014 · Cited by 32
Pharmacotherapy of Diabetes: New Developments
Mogensen, C. E. (2007) · Springer eBooks · doi:10.1007/978-0-387-69737-6 · Cited by 30
Metformin: A candidate for the treatment of gynecological tumors based on drug repositioning
Irie, H., Banno, K., Yanokura, M., Iida, M., Adachi, M., Nakamura, K., Umene, K., Nogami, Y., Masuda, K., Kobayashi, Y., et al. (2016) · Oncology Letters · doi:10.3892/ol.2016.4075 · Cited by 32
Metformin Enhances the Therapy Effects of Anti-IGF-1R mAb Figitumumab to NSCLC
Cao, H., Dong, W., Qu, X. H., Shen, H., Xu, J., Zhu, L., Liu, Q., & Du, J. (2016) · Scientific Reports · doi:10.1038/srep31072 · Cited by 30
The Role of AMPK/mTOR Modulators in the Therapy of Acute Myeloid Leukemia
Višnjić, D., Dembitz, V., & Lalić, H. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180117105522 · Cited by 28
Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin
Abdelrahman, S., Alghrably, M., Campagna, M., Hauser, C. A. E., Jaremko, M., & Lachowicz, J. I. (2021) · Molecules · doi:10.3390/molecules26164730 · Cited by 29
Metformin and ICG-001 Act Synergistically to Abrogate Cancer Stem Cells-Mediated Chemoresistance in Colorectal Cancer by Promoting Apoptosis and Autophagy
Roy, S., Zhao, Y., Yuan, Y., & Goel, A. (2022) · Cancers · doi:10.3390/cancers14051281 · Cited by 30
Metformin reverses tamoxifen resistance through the lncRNA GAS5-medicated mTOR pathway in breast cancer
Jiang, Y., Qian, T., Li, S., Xie, Y., & Tao, M. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-795 · Cited by 29
LKB1 expression is inhibited by estradiol-17β in MCF-7 cells
Brown, K. A., McInnes, K. J., Takagi, K., Ono, K., Hunger, N. I., Wang, L., Sasano, H., & Simpson, E. R. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.06.005 · Cited by 29
Metformin suppresses the expression of Sonic hedgehog in gastric cancer cells
Song, Z., Wei, B., Lu, C., Huang, X., Li, P., & Chen, L. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6205 · Cited by 29
A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index
Zell, J. A., McLaren, C. E., Morgan, T. R. M., Lawson, M. J., Rezk, S. A., Albers, G. C., Chen, W., Carmichael, J. C., Chung, J., Richmond, E. S., et al. (2019) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-18-0262 · Cited by 29
Self-citation
Points of integration between the intracellular energy sensor AMP-activated protein kinase (AMPK) activity and the somatotroph axis function
Tulipano, G., Faggi, L., Sibilia, V., & Giustina, A. (2012) · Endocrine · doi:10.1007/s12020-012-9732-x · Cited by 28
In VitroandIn VivoEffects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue
Śmieszek, A., Basińska, K., Chrząstek, K., & Marycz, K. (2015) · Journal of Diabetes Research · doi:10.1155/2015/814896 · Cited by 29
Pleiotropic effects of nutritional ketosis: Conceptual framework for keto-adaptation as a breast cancer therapy
Hyde, P. N., Lustberg, M. B., Miller, V. J., LaFountain, R. A., & Volek, J. S. (2017) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2017.06.001 · Cited by 28
Fertility-Sparing Management Using Progestin for Young Women with Endometrial Cancer From a Population-Based Study
Kim, S. R., van der Zanden, C., Ikiz, H., Kuzelijevic, B., Havelock, J. C., & Kwon, J. S. (2017) · Journal of Obstetrics and Gynaecology Canada · doi:10.1016/j.jogc.2017.06.037 · Cited by 28
Evaluation of antagonistic effects of metformin with Cisplatin in gastric cancer cells.
Lesan, V., Ghaffari, S. H., Salaramoli, J., Heidari, M., Rostami, M., Alimoghaddam, K., & Ghavamzadeh, A. (2014) · Europe PMC (PubMed Central) · Cited by 28
Metformin in lung cancer: rationale for a combination therapy
Morgillo, F., Sasso, F. C., Corte, C. M. D., Festino, L., Manzo, A., Martinelli, E., Troiani, T., Capuano, A., & Ciardiello, F. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2013.828691 · Cited by 29
Commonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literature
Wu, J. W., Boudreau, D. M., Park, Y., Simonds, N. I., & Freedman, A. N. (2014) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2014.926887 · Cited by 27
Metformin and the risk of head and neck cancer: a case–control analysis
Becker, C., Jick, S. S., Meier, C. R., & Bodmer, M. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12351 · Cited by 27
Targeting breast cancer through its microenvironment: Current status of preclinical and clinical research in finding relevant targets
Nienhuis, H. H., Gaykema, S. B. M., Timmer‐Bosscha, H., Jalving, M., Brouwers, A. H., Hooge, M. N. L., van der Vegt, B., Overmoyer, B. A., de Vries, E. G. E., & Schroder, C. P. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.11.004 · Cited by 29
Metformin induces degradation of mTOR protein in breast cancer cells
Alalem, M. A., Ray, A., & Ray, B. K. (2016) · Cancer Medicine · doi:10.1002/cam4.896 · Cited by 27
Metformin inhibits the proliferation of benign prostatic epithelial cells
Wang, Z., Xiao, X., Ge, R., Li, J., Johnson, C. W., Rassoulian, C., & Olumi, A. F. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173335 · Cited by 28
Retracted
AMPK activation overcomes anti-EGFR antibody resistance induced by KRAS mutation in colorectal cancer
Ye, H., Liu, Y., Wu, K., Luo, H., & Cui, L. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00584-z · Cited by 27

Authors: Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N., & Pollak, M.
Affiliations: 1Oncology and Departments of
McGill University (CA)
Mount Sinai Hospital (CA)
ORCID: Dowling, Ryan
Sonenberg, Nahum
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2006-11-01
Volume: 66
Issue: 21
Pages: 10269-10273
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-06-1500
OpenAlex: W2078190084
Cited by: 1,048
References: 20
Citations by year: 2026: 13 · 2025: 11 · 2024: 24 · 2023: 29 · 2022: 28 · 2021: 54 · 2020: 47 · 2019: 62 · 2018: 55 · 2017: 70 · 2016: 70 · 2015: 80 · 2014: 93 · 2013: 86 · 2012: 85
FWCI: 12.76
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
eScholarship@McGill (McGill) (submittedVersion)
Funders: Canadian Breast Cancer Research Alliance
Terry Fox Foundation
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, AMP kinase, breast cancer, cell growth inhibition, antineoplastic effects, mTOR, S6 kinase, mRNA translation, insulin resistance, insulin-like growth factor, epithelial cells, cancer prevention
MeSH terms: Adenylate Kinase, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Insulin, Metformin, Protein Biosynthesis, Gene Expression Regulation, Enzymologic, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks