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 301–400 of 1,000

Reversion of Multidrug Resistance by Co-Encapsulation of Doxorubicin and Metformin in Poly(lactide-co-glycolide)-d-α-tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles
Shafiei‐Irannejad, V., Samadi, N., Salehi, R., Yousefi, B., Rahimi, M., Akbarzadeh, A., & Zarghami, N. (2018) · Pharmaceutical Research · doi:10.1007/s11095-018-2404-7 · Cited by 80
The Heterogeneity of Lipid Metabolism in Cancer
Park, J. K., Coffey, N. J., Limoges, A., & Le, A. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-77736-8_3 · Cited by 80
Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents
Modica-Napolitano, J. S., & Weissig, V. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160817394 · Cited by 80
Insulin, insulin-like growth factors, insulin resistance, and neoplasia
Pollak, M. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.3.820s · Cited by 78
Self-citation
Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase
Bridges, H. R., Sirviö, V. A., Agip, A.-N. A., & Hirst, J. (2016) · BMC Biology · doi:10.1186/s12915-016-0287-9 · Cited by 82
AMPK Activators Suppress Cervical Cancer Cell Growth through Inhibition of DVL3 Mediated Wnt/β-Catenin Signaling Activity
Kwan, H., Chan, D. W., Cai, P. C. H., Mak, C. S. L., Yung, M. M. H., Leung, T. H. Y., Wong, O. G., Cheung, A., & Ngan, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053597 · Cited by 81
Emerging evidence for targeting mitochondrial metabolic dysfunction in cancer therapy
Zhu, Y., Dean, A. E., Horikoshi, N., Heer, C. D., Spitz, D. R., & Gius, D. R. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120844 · Cited by 82
AMP-Activated Protein Kinase 2 Isoform Suppression in Primary Breast Cancer Alters AMPK Growth Control and Apoptotic Signaling
Fox, M. M., Phoenix, K. N., Kopsiaftis, S., & Claffey, K. P. (2013) · Genes & Cancer · doi:10.1177/1947601913486346 · Cited by 79
Breast Cancer Chemoprevention: Old and New Approaches
Cazzaniga, M., & Bonanni, B. (2012) · BioMed Research International · doi:10.1155/2012/985620 · Cited by 82
Energy Homeostasis and Cancer Prevention: The AMP-Activated Protein Kinase
Fay, J. R., Steele, V. E., & Crowell, J. A. (2009) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0166 · Cited by 77
Presurgical Trial of Metformin in Overweight and Obese Patients with Newly Diagnosed Breast Cancer
Kalinsky, K. M., Crew, K. D., Refice, S., Xiao, T., Wang, A., Feldman, S. M., Taback, B., Ahmad, A., Cremers, S., Hibshoosh, H. H., et al. (2014) · Cancer Investigation · doi:10.3109/07357907.2014.889706 · Cited by 79
Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P‐gp‐overexpressing MCF‐7 cells
Shafiei‐Irannejad, V., Samadi, N., Yousefi, B., Salehi, R., Velaei, K., & Zarghami, N. (2017) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13078 · Cited by 78
Metformin suppresses cancer cell growth in endometrial carcinoma by inhibiting PD-L1
Xue, J., Li, L., Li, N., Li, F., Qin, X., Li, T., & Liu, M. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172541 · Cited by 77
Insulin in the Adjuvant Breast Cancer Setting: A Novel Therapeutic Target for Lifestyle and Pharmacologic Interventions?
Goodwin, P. J. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.7132 · Cited by 77
Metformin prevents cell tumorigenesis through autophagy-related cell death
Santi, M. D., Baldelli, G., Diotallevi, A., Galluzzi, L., Schiavano, G. F., & Brandi, G. (2019) · Scientific Reports · doi:10.1038/s41598-018-37247-6 · Cited by 79
BRCA1 and acetyl‐CoA carboxylase: The metabolic syndrome of breast cancer
Brunet, J., Vázquez‐Martín, A., Colomer, R., Graña-Suárez, B., Martı́n-Castillo, B., & Menéndez, J. A. (2007) · Molecular Carcinogenesis · doi:10.1002/mc.20364 · Cited by 76
The Effect of Metformin on Alveolar Bone in Ligature‐Induced Periodontitis in Rats: A Pilot Study
Bak, E., Park, H. G., Kim, M., Kim, S. W., Kim, S., Choi, S., Cha, J., & Yoo, Y. (2010) · Journal of Periodontology · doi:10.1902/jop.2009.090414 · Cited by 79
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells
Loubière, C., Clavel, S., Gilleron, J., Harisseh, R., Fauconnier, J., Ben‐Sahra, I., Kaminski, L., Laurent, K., Herkenne, S., Lacas‐Gervais, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-05052-2 · Cited by 77
Selectively Starving Cancer Cells Through Dietary Manipulation: Methods and Clinical Implications
Simone, B. A., Champ, C. E., Rosenberg, A., Berger, A. C., Monti, D., Dicker, A. P., & Simone, N. L. (2013) · Future Oncology · doi:10.2217/fon.13.31 · Cited by 78
Insulin, Insulin Resistance, Obesity, and Cancer
Gallagher, E. J., & LeRoith, D. (2010) · Current Diabetes Reports · doi:10.1007/s11892-010-0101-y · Cited by 76
Antidiabetic Drug Metformin Suppresses Endotoxin-Induced Uveitis in Rats
Kalariya, N. M., Shoeb, M., Ansari, N. H., Sk, S., & Ramana, K. V. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-9432 · Cited by 74
Metformin exhibits antiproliferation activity in breast cancer via miR-483-3p/METTL3/m6A/p21 pathway
Cheng, L., Zhang, X., Huang, Y., Zhu, Y., Xu, L.-Y., Li, Z., Dai, X., Shi, L., Zhou, S., Wei, J., et al. (2021) · Oncogenesis · doi:10.1038/s41389-020-00290-y · Cited by 73
EglN2 associates with the NRF1‐PGC1α complex and controls mitochondrial function in breast cancer
Zhang, J., Wang, C., Chen, X., Takada, M., Fan, C., Zheng, X., Wen, H., Liu, Y., Wang, C., Pestell, R. G., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201591437 · Cited by 76
Metformin synergistically suppress tumor growth with doxorubicin and reverse drug resistance by inhibiting the expression and function of P-glycoprotein in MCF7/ADR cells and xenograft models
Li, Y., Wang, M., Zhi, P., You, J., & Gao, J. (2017) · Oncotarget · doi:10.18632/oncotarget.23187 · Cited by 75
Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression
Xia, C., Liu, C., He, Z., Cai, Y., & Chen, J. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01627-6 · Cited by 75
Recent Progress on Liver Kinase B1 (LKB1): Expression, Regulation, Downstream Signaling and Cancer Suppressive Function
Gan, R., & Li, H. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150916698 · Cited by 76
A spatiotemporal hypothesis for the regulation, role, and targeting of AMPK in prostate cancer
Khan, A., & Frigo, D. E. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2016.272 · Cited by 74
Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells
Mishra, A. K., & Dingli, D. (2019) · Leukemia · doi:10.1038/s41375-019-0470-4 · Cited by 72
Interfering with Metabolic Profile of Triple‐Negative Breast Cancers Using Rationally Designed Metformin Prodrugs
Babak, M. V., Chong, K. R., Rapta, P., Ζαννίκου, Μ., Tang, H. M., Reichert, L., Chang, M. R., Kushnarev, V. A., Heffeter, P., Meier, S. M., et al. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202102266 · Cited by 72
Obesity and insulin resistance in breast cancer – Chemoprevention strategies with a focus on metformin
Goodwin, P. J., & Stambolic, V. (2011) · The Breast · doi:10.1016/s0960-9776(11)70291-0 · Cited by 71
Risk of Cancer in Diabetes: The Effect of Metformin
Malek, M., Aghili, R., Emami, Z., & Khamseh, M. E. (2013) · ISRN Endocrinology · doi:10.1155/2013/636927 · Cited by 73
Metformin Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells
Cheng, K., & Hao, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122000 · Cited by 70
Effects of metformin on clinical outcome in diabetic patients with advanced HCC receiving sorafenib
Gardini, A. C., Marisi, G., Scarpi, E., Scartozzi, M., Faloppi, L., Silvestris, N., Masi, G., Vivaldi, C., Brunetti, O., Tamberi, S., et al. (2015) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2015.1102887 · Cited by 69
Metformin as an antitumor agent in cancer prevention and treatment
Li, D. (2011) · Journal of Diabetes · doi:10.1111/j.1753-0407.2011.00119.x · Cited by 68
Metformin Induces Apoptosis and Alters Cellular Responses to Oxidative Stress in Ht29 Colon Cancer Cells: Preliminary Findings
Sena, P., Mancini, S., Benincasa, M., Mariani, F., Palumbo, C., & Roncucci, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051478 · Cited by 70
The Epidemiology and Molecular Mechanisms Linking Obesity, Diabetes, and Cancer
Ferguson, R. D., Gallagher, E. J., Scheinman, E. J., Damouni, R., & LeRoith, D. (2013) · Vitamins and hormones · doi:10.1016/b978-0-12-416673-8.00010-1 · Cited by 72
Chemoprevention of Hormone Receptor-Negative Breast Cancer: New Approaches Needed
Uray, I. P., & Brown, P. H. (2010) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-10858-7_13 · Cited by 68
In vitro and in vivo antitumoral action of metformin on hepatocellular carcinoma
Qu, Z., Zhang, Y., Liao, M., Chen, Y., Zhao, J., & Pan, Y. (2012) · Hepatology Research · doi:10.1111/j.1872-034x.2012.01007.x · Cited by 68
Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)
Kim, J., Lim, W., Kim, E., Kim, M.-K., Paik, N.-S., Jeong, S.-S., Yoon, J.-H., Park, C. H., Ahn, S. H., Kim, L. S., et al. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-170 · Cited by 68
Curcumin and metformin‐mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells
Siddappa, G., Kulsum, S., Ravindra, D. R., Kumar, V. V., Raju, N., Raghavan, N., Sudheendra, H. V., Sharma, A., Sunny, S. P., Jacob, T., et al. (2017) · Molecular Carcinogenesis · doi:10.1002/mc.22692 · Cited by 68
Metformin from mother to unborn child-are there unwarranted effects?
Nguyen, L., Chan, S.-Y., & Teo, A. K. K. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.08.047 · Cited by 67
Metformin limits ceramide-induced senescence in C2C12 myoblasts
Jadhav, K. S., Dungan, C. M., & Williamson, D. L. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.11.002 · Cited by 67
The use of metformin is associated with decreased lumbar radiculopathy pain
Guruguri, T., Taylor, A., Westveld, A. H., Szkudlinska, M. A., Annabi, E. H., Patwardhan, A. M., Yassine, H. N., & Guruguri, P. (2013) · Journal of Pain Research · doi:10.2147/jpr.s52205 · Cited by 66
Improving treatment for obese women with early stage cancer of the uterus: Rationale and design of the levonorgestrel intrauterine device±Metformin±weight loss in endometrial cancer (feMME) trial
Hawkes, A. L., Quinn, M. A., Gebski, V., Armes, J. E., Brennan, D. J., Janda, M., & Obermair, A. (2014) · Contemporary Clinical Trials · doi:10.1016/j.cct.2014.06.014 · Cited by 67
Metformin inhibits inflammatory angiogenesis in a murine sponge model
Xavier, D. O., Amaral, L. S. D. B., Gomes, M. A., Rocha, M. A., Campos, P. R., Cota, B. D. C. V., Tafuri, L., Paiva, A., Silva, J. H., Andrade, S. P., et al. (2009) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2009.08.004 · Cited by 70
Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions
Vazquez-Martin, A., López-Bonetc, E., Cufí, S., Oliveras-Ferraros, C., Del Barco, S., Martin-Castillo, B., & Menendez, J. A. (2011) · Drug Resistance Updates · doi:10.1016/j.drup.2011.04.003 · Cited by 66
Personalized therapy in endometrial cancer: Challenges and opportunities
Westin, S. N., & Broaddus, R. R. (2012) · Cancer Biology & Therapy · doi:10.4161/cbt.13.1.18438 · Cited by 66
The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy
Choi, Y., Kim, T.-Y., Oh, D., Lee, K.-H., Han, S., Im, S., Kim, T., & Bang, Y. (2015) · Cancer Research and Treatment · doi:10.4143/crt.2014.292 · Cited by 65
Decreased PCSK9 expression in human hepatocellular carcinoma
Bhat, M., Skill, N. J., Marcus, V., Deschênes, M., Tan, X. M., Bouteaud, J., Negi, S., Awan, Z. A., Aikin, R. A., Kwan, J., et al. (2015) · BMC Gastroenterology · doi:10.1186/s12876-015-0371-6 · Cited by 65
Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis
Liu, Q., Yuan, W., Tong, D., Liu, G., Lan, W., Zhang, D., Xiao, H., Zhang, Y., Huang, Z., Yang, J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8595 · Cited by 65
AMPK inhibitor compound C suppresses cell proliferation by induction of apoptosis and autophagy in human colorectal cancer cells
Yang, W., Perillo, W., Liou, D., Marambaud, P., & Wang, P. (2012) · Journal of Surgical Oncology · doi:10.1002/jso.23184 · Cited by 65
New Molecules and Old Drugs as Emerging Approaches to Selectively Target Human Glioblastoma Cancer Stem Cells
Würth, R., Barbieri, F., & Florio, T. (2014) · BioMed Research International · doi:10.1155/2014/126586 · Cited by 69
Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients
Ochoa-González, F. D. L., Cervantes-Villagrana, A. R., Fernández-Ruiz, J. C., Nava-Ramirez, H. S., Hernandez-Correa, A. C., Enciso‐Moreno, J. A., & Castañeda‐Delgado, J. E. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150900 · Cited by 64
Metabolic synthetic lethality in cancer therapy
Zecchini, V. R., & Frezza, C. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.12.003 · Cited by 63
Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases
Huang, Q.-Y., Lai, X., Qian, X., Lv, L., Li, J., Duan, J., Xiao, X., & Xiong, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20010179 · Cited by 67
Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer
Fan, C., Wang, Y., LIU, Z., Sun, Y. H., Wang, X., Wei, G., & Wei, J. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2217 · Cited by 64
Retracted
Autophagy Function and Dysfunction: Potential Drugs as Anti-Cancer Therapy
Cuomo, F., Altucci, L., & Cobellis, G. (2019) · Cancers · doi:10.3390/cancers11101465 · Cited by 64
Targeting the LKB1 Tumor Suppressor
Zhao, R., & Xu, Z. (2014) · Current Drug Targets · doi:10.2174/1389450114666140106095811 · Cited by 64
Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma
Ma, J., Guo, Y. H., Chen, S., Zhong, C., Xue, Y., Zhang, Y., Lai, X., Wei, Y., Yu, S., Zhang, J., et al. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-172 · Cited by 63
A randomized phase II study of aromatase inhibitors plus metformin in pre-treated postmenopausal patients with hormone receptor positive metastatic breast cancer
Zhao, Y., Gong, C., Wang, Z., Zhang, J., Wang, L., Zhang, S., Cao, J., Tao, Z., Li, T., Wang, B., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20478 · Cited by 64
Diabetes Mellitus and Colorectal Cancer Risk
Kallergi, A., Chambre, C., Duchemann, B., Fysekidis, M., & Bihan, H. (2015) · Current Colorectal Cancer Reports · doi:10.1007/s11888-015-0274-5 · Cited by 61
Metformin and Colorectal Cancer
Higurashi, T., & Nakajima, A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00622 · Cited by 63
Metformin and Cancer
Vallianou, N. G., Evangelopoulos, A. A., & Kazazis, C. E. (2013) · The Review of Diabetic Studies · doi:10.1900/rds.2013.10.228 · Cited by 59
mTOR inhibitors and the anti-diabetic biguanide metformin: new insights into the molecular management of breast cancer resistance to the HER2 tyrosine kinase inhibitor lapatinib (Tykerb®)
Vázquez‐Martín, A., Oliveras‐Ferraros, C., Barco, S. D., Martı́n-Castillo, B., & Menéndez, J. A. (2009) · Clinical & Translational Oncology · doi:10.1007/s12094-009-0384-0 · Cited by 60
Focus on Cdc42 in Breast Cancer: New Insights, Target Therapy Development and Non-Coding RNAs
Zhang, Y., Li, J., Lai, X., Jiao, X., Xiong, J., & Xiong, L. (2019) · Cells · doi:10.3390/cells8020146 · Cited by 63
Metformin-containing hydrogel scaffold to augment CAR-T therapy against post-surgical solid tumors
Chao, Y., Wei, T., Li, Q., Liu, B., Hao, Y., Chen, M., Wu, Y., Song, F., Chen, Q., & Liu, Z. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122052 · Cited by 60
Combined Use of Vitamin D3 and Metformin Exhibits Synergistic Chemopreventive Effects on Colorectal Neoplasia in Rats and Mice
Wan, L., Wang, Q.-L., Liu, X., Dong, S.-H., Li, H.-X., Li, C., Guo, L.-S., Gao, J.-M., Berger, N. A., Li, L., et al. (2014) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-14-0128 · Cited by 60
Statin Use as a Moderator of Metformin Effect on Risk for Prostate Cancer Among Type 2 Diabetic Patients
Lehman, D. M., Lorenzo, C., Hernández, J., & Wang, C.-P. (2012) · Diabetes Care · doi:10.2337/dc11-1829 · Cited by 58
Phenformin-loaded polymeric micelles for targeting both cancer cells and cancer stem cells in vitro and in vivo
Krishnamurthy, S., Ng, V. W. L., Gao, S., Tan, M., & Yang, Y. Y. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.07.018 · Cited by 59
Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy
Zhang, Y., Storr, S. J., Johnson, K., Green, A. R., Rakha, E. A., Ellis, I. O., Morgan, D. A. L., & Martin, S. G. (2014) · Oncotarget · doi:10.18632/oncotarget.2683 · Cited by 59
In vitro and in vivo antiproliferative activity of metformin on stem-like cells isolated from spontaneous canine mammary carcinomas: translational implications for human tumors
Barbieri, F., Thellung, S., Ratto, A., Carra, E., Marini, V., Fucile, C., Bajetto, A., Pattarozzi, A., Würth, R., Gatti, M., et al. (2015) · BMC Cancer · doi:10.1186/s12885-015-1235-8 · Cited by 61
The antidiabetic drug metformin: a pharmaceutical AMPK activator to overcome breast cancer resistance to HER2 inhibitors while decreasing risk of cardiomyopathy
Vázquez‐Martín, A., Oliveras‐Ferraros, C., del Barco, S., Martı́n-Castillo, B., & Menéndez, J. A. (2009) · Annals of Oncology · doi:10.1093/annonc/mdn758 · Cited by 58
Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells
Soo, J. S.-S., Ng, C., Tan, S. H., Malik, R. A., Teh, Y.-C., Tan, B.-S., Ho, G. F., See, M., Taib, N. A. M., Yip, C. H., et al. (2015) · APOPTOSIS · doi:10.1007/s10495-015-1158-5 · Cited by 58
Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase
Guo, Q., Liu, Z., Jiang, L., Liu, M., Ma, J., Yang, C., Han, L., Nan, K., & Liang, X. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4830 · Cited by 59
Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells.
Jafari-Gharabaghlou, D., Pilehvar‐Soltanahmadi, Y., Dadashpour, M., Mota, A., Vafajouy-Jamshidi, S., Faramarzi, L., Rasouli, S., & Zarghami, N. (2018) · Europe PMC (PubMed Central) · doi:10.22038/ijbms.2018.30460.7345 · Cited by 58
High Glucose Represses the Anti-Proliferative and Pro-Apoptotic Effect of Metformin in Triple Negative Breast Cancer Cells
Varghese, S., Samuel, S. M., Varghese, E., Kubatka, P., & Büsselberg, D. (2019) · Biomolecules · doi:10.3390/biom9010016 · Cited by 58
Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis
Wan, G., Sun, X., Li, F., Wang, X., Li, C., Li, H., Yu, X., & Cao, F. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000493214 · Cited by 57
Secular trend for mortality from breast cancer and the association between diabetes and breast cancer in Taiwan between 1995 and 2006
Tseng, C., Chong, C.-K., & Tai, T. Y. (2008) · Diabetologia · doi:10.1007/s00125-008-1204-8 · Cited by 57
“Overcoming breast cancer drug resistance with mTOR inhibitors”. Could it be a myth or a real possibility in the short-term future?
Margariti, N., Fox, S. B., Bottini, A., & Generali, D. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-0986-9 · Cited by 57
Metformin Inhibits Skin Tumor Promotion in Overweight and Obese Mice
Checkley, L. A., Rho, O., Angel, J. M., Cho, J., Blando, J. M., Beltrán, L., Hursting, S. D., & DiGiovanni, J. (2013) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-13-0110 · Cited by 57
The phenomenon of acquired resistance to metformin in breast cancer cells: The interaction of growth pathways and estrogen receptor signaling
Scherbakov, A. M., Sorokin, D. V., Tatarskiy, V. V., Prokhorov, N. S., Semina, S. E., Berstein, L. M., & Ma, K. (2016) · IUBMB Life · doi:10.1002/iub.1481 · Cited by 57
Metformin and Cancer, an Ambiguanidous Relationship
Skuli, S. J., Alomari, S., Gaitsch, H., Bakayoko, A., Skuli, N., & Tyler, B. (2022) · Pharmaceuticals · doi:10.3390/ph15050626 · Cited by 60
Association between Gastroenterological Malignancy and Diabetes Mellitus and Anti-Diabetic Therapy: A Nationwide, Population-Based Cohort Study
Lin, C., Huang, H., Chu, F.-Y., Fan, H., Chen, H.-A., Chu, D., Wu, L., Wang, C., Chen, W., Lin, S., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125421 · Cited by 56
Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways
Pan, Q., Yang, G., Yang, J., Lin, S., Liu, N., Liu, S., Liu, M., Zhang, L., Huang, Y., Shen, R. Z., et al. (2015) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-015-0183-0 · Cited by 56
Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial
Higurashi, T., Takahashi, H., Endo, H., Hosono, K., Yamada, E., Ohkubo, H., Sakai, E., Uchiyama, T., Hata, Y., Fujisawa, N., et al. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-118 · Cited by 55
Antiproliferative Effect of Metformin on the Endometrium - a Clinical Trial
Tabrizi, A. D., Sayyah-Melli, M., Foroughi, M., Ghojazadeh, M., & Bidadi, S. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.23.10067 · Cited by 57
The expanding role of metformin in cancer: an update on antitumor mechanisms and clinical development
Gong, J., Kelekar, G., Shen, J., Shen, J., Kaur, S., & Mita, M. M. (2016) · Targeted Oncology · doi:10.1007/s11523-016-0423-z · Cited by 56
How good are publicly available web services that predict bioactivity profiles for drug repurposing?
Murtazalieva, K. A., Druzhilovskiy, D. S., Goel, R. K., Sastry, G. N., & Poroikov, V. (2017) · SAR and QSAR in environmental research · doi:10.1080/1062936x.2017.1399448 · Cited by 54
Development of a Magnetic Nanostructure for Co-delivery of Metformin and Silibinin on Growth of Lung Cancer Cells: Possible Action Through Leptin Gene and its Receptor Regulation
Salmani-Javan, E., Lotfi, F., Jafari-Gharabaghlou, D., Mousazadeh, H., Dadashpour, M., & Zarghami, N. (2022) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2022.23.2.519 · Cited by 54
Metformin use is associated with a decreased incidence of colorectal adenomas in diabetic patients with previous colorectal cancer
Lee, J. H., Jeon, S. M., Hong, S. P., Cheon, J. H., Kim, T. I., & Kim, W. H. (2012) · Digestive and Liver Disease · doi:10.1016/j.dld.2012.06.007 · Cited by 53
Metformin: A Diabetes Drug for Cancer, or a Cancer Drug for Diabetics?
Martin, M. J., & Marais, R. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.1677 · Cited by 54
Obese Adipose Tissue as a Driver of Breast Cancer Growth and Development: Update and Emerging Evidence
Bhardwaj, P., & Brown, K. A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.638918 · Cited by 54
A phase I study of temsirolimus and metformin in advanced solid tumours
MacKenzie, M. J., Ernst, S., Johnson, C., & Winquist, E. (2010) · Investigational New Drugs · doi:10.1007/s10637-010-9570-8 · Cited by 53
Current Status and Challenges Associated with Targeting mTOR for Cancer Therapy
Dowling, R. J. O., Pollak, M., & Sonenberg, N. (2009) · BioDrugs · doi:10.2165/00063030-200923020-00002 · Cited by 52
Self-citation
Polypeptide Derivative of Metformin with the Combined Advantage of a Gene Carrier and Anticancer Activity
Ramasamy, T., Ruttala, H. B., Kaliraj, K., Poudel, K., Jin, S. G., Choi, H., Ku, S., Yong, C. S., & Kim, J. O. (2019) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b00982 · Cited by 53
Isolated and combined action of tamoxifen and metformin in wild-type, tamoxifen-resistant, and estrogen-deprived MCF-7 cells
Berstein, L. M., Yue, W., Wang, J., & Santen, R. J. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-1072-z · Cited by 55
The anti-diabetic drug metformin inhibits vascular endothelial growth factor expression via the mammalian target of rapamycin complex 1/hypoxia-inducible factor-1α signaling pathway in ELT-3 cells
Tadakawa, M., Takeda, T., Li, B., Tsuiji, K., & Yaegashi, N. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.08.012 · Cited by 54
Antitumor effect of metformin in esophageal cancer: In vitro study
Kobayashi, M., Kato, K., Iwama, H., Fujihara, S., Nishiyama, N., Mimura, S., Toyota, Y., Nomura, T., NOMURA, K., Tani, J., et al. (2012) · International Journal of Oncology · doi:10.3892/ijo.2012.1722 · Cited by 52
Metformin inhibits estrogen‐dependent endometrial cancer cell growth by activating the AMPK – FOXO 1 signal pathway
Zou, J., Hong, L., Luo, C., Li, Z., Zhu, Y., Huang, T., Zhang, Y., Yuan, H., Hu, Y., Wen, T., et al. (2016) · Cancer Science · doi:10.1111/cas.13083 · Cited by 53
New insights into antidiabetic drugs: Possible applications in cancer treatment
Shafiei‐Irannejad, V., Samadi, N., Salehi, R., Yousefi, B., & Zarghami, N. (2017) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13013 · Cited by 52

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