Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug?

Lalau, 1999, Lactic acidosis in metformin therapy, Drugs, 58, 55, 10.2165/00003495-199958001-00013

Chen, 2009, Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, Proc Natl Acad Sci U S A, 106, 3907, 10.1073/pnas.0807991106

Zhou, 2001, Role of AMP-activated protein kinase in mechanism of metformin action, J Clin Invest, 108, 1167, 10.1172/JCI13505

Shaw, 2005, The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin, Science, 310, 1642, 10.1126/science.1120781

Kozka, 1995, The effects of insulin on the level and activity of the GLUT4 present in human adipose cells, Diabetologia, 38, 661, 10.1007/BF00401836

Evans, 2005, Metformin and reduced risk of cancer in diabetic patients, BMJ, 330, 1304, 10.1136/bmj.38415.708634.F7

Bowker, 2006, Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin, Diabetes Care, 29, 254, 10.2337/diacare.29.02.06.dc05-1558

Libby, 2009, New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes, Diabetes Care, 32, 1620, 10.2337/dc08-2175

Murtola, 2008, Antidiabetic medication and prostate cancer risk: a population-based case-control study, Am J Epidemiol, 168, 925, 10.1093/aje/kwn190

Jiralerspong, 2009, Expanding the arsenal: metformin for the treatment of triple-negative breast cancer?, Cell Cycle, 8, 2681, 10.4161/cc.8.17.9502

Calle, 2004, Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms, Nat Rev Cancer, 4, 579, 10.1038/nrc1408

Yang, 2004, Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients, Gastroenterology, 127, 1044, 10.1053/j.gastro.2004.07.011

Lipscombe, 2006, Increased prevalence of prior breast cancer in women with newly diagnosed diabetes, Breast Cancer Res Treat, 98, 303, 10.1007/s10549-006-9166-3

Pollak, 2008, Insulin and insulin-like growth factor signalling in neoplasia, Nat Rev Cancer, 8, 915, 10.1038/nrc2536

Marshall, 2006, Role of insulin, adipocyte hormones, and nutrient-sensing pathways in regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer, Sci STKE, re7

Tosca, 2010, Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells, Reproduction, 139, 409, 10.1530/REP-09-0351

Long, 2006, AMP-activated protein kinase signaling in metabolic regulation, J Clin Invest, 116, 1776, 10.1172/JCI29044

Forcet, 2007, Dialogue between LKB1 and AMPK: a hot topic at the cellular pole, Sci STKE, pe51

Hardie, 2003, Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status, Endocrinology, 144, 5179, 10.1210/en.2003-0982

Bolster, 2002, AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling, J Biol Chem, 277, 23977, 10.1074/jbc.C200171200

Dowling, 2007, Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells, Cancer Res, 67, 10804, 10.1158/0008-5472.CAN-07-2310

Zakikhani, 2006, Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells, Cancer Res, 66, 10269, 10.1158/0008-5472.CAN-06-1500

Gotlieb, 2008, In vitro metformin anti-neoplastic activity in epithelial ovarian cancer, Gynecol Oncol, 110, 246, 10.1016/j.ygyno.2008.04.008

Huang, 2008, Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice, Biochem J, 412, 211, 10.1042/BJ20080557

Ben Sahra, 2008, The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level, Oncogene, 27, 3576, 10.1038/sj.onc.1211024

Guigas, 2006, 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation, Diabetes, 55, 865, 10.2337/diabetes.55.04.06.db05-1178

Jones, 2005, AMP-activated protein kinase induces a p53-dependent metabolic checkpoint, Mol Cell, 18, 283, 10.1016/j.molcel.2005.03.027

Okoshi, 2008, Activation of AMP-activated protein kinase induces p53-dependent apoptotic cell death in response to energetic stress, J Biol Chem, 283, 3979, 10.1074/jbc.M705232200

Feng, 2007, The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways, Cancer Res, 67, 3043, 10.1158/0008-5472.CAN-06-4149

Bensaad, 2007, p53: new roles in metabolism, Trends Cell Biol, 17, 286, 10.1016/j.tcb.2007.04.004

Buzzai, 2007, Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth, Cancer Res, 67, 6745, 10.1158/0008-5472.CAN-06-4447

Zhuang, 2008, Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1, J Mol Signal, 3, 18, 10.1186/1750-2187-3-18

Hirsch, 2009, Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission, Cancer Res, 69, 7507, 10.1158/0008-5472.CAN-09-2994

Alimova, 2009, Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro, Cell Cycle, 8, 909, 10.4161/cc.8.6.7933

Liu, 2009, Metformin induces unique biological and molecular responses in triple negative breast cancer cells, Cell Cycle, 8, 2031, 10.4161/cc.8.13.8814

Wang, 2008, Metformin induces apoptosis of pancreatic cancer cells, World J Gastroenterol, 14, 7192, 10.3748/wjg.14.7192

Vazquez-Martin, 2009, The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells, Cell Cycle, 8, 88, 10.4161/cc.8.1.7499

Kisfalvi, 2009, Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth, Cancer Res, 69, 6539, 10.1158/0008-5472.CAN-09-0418

Schneider, 2001, Prevention of pancreatic cancer induction in hamsters by metformin, Gastroenterology, 120, 1263, 10.1053/gast.2001.23258

Anisimov, 2005, Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice, Exp Gerontol, 40, 685, 10.1016/j.exger.2005.07.007

Tomimoto, 2008, Metformin suppresses intestinal polyp growth in Apc(Min/+) mice, Cancer Sci, 99, 2136, 10.1111/j.1349-7006.2008.00933.x

Algire, 2008, Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth, Endocr Relat Cancer, 15, 833, 10.1677/ERC-08-0038

Phoenix, 2009, Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model, Breast Cancer Res Treat, 113, 101, 10.1007/s10549-008-9916-5

Rae, 2007, MDA-MB-435 cells are derived from M14 melanoma cells-a loss for breast cancer, but a boon for melanoma research, Breast Cancer Res Treat, 104, 13, 10.1007/s10549-006-9392-8

Cazzaniga, 2009, Is it time to test metformin in breast cancer clinical trials?, Cancer Epidemiol Biomarkers Prev, 18, 701, 10.1158/1055-9965.EPI-08-0871

Goodwin, 2009, Metformin in breast cancer: time for action, J Clin Oncol, 27, 3271, 10.1200/JCO.2009.22.1630

Martin-Castillo, 2010, Incorporating the antidiabetic drug metformin in HER2-positive breast cancer treated with neo-adjuvant chemotherapy and trastuzumab: an ongoing clinical-translational research experience at the Catalan Institute of Oncology, Ann Oncol, 21, 187, 10.1093/annonc/mdp494

Pongchaidecha, 2004, Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: a cross-sectional study in patients with type 2 diabetes mellitus, J Med Assoc Thai, 87, 780

Goldhirsch, 1987, Methotrexate/nitrous-oxide toxic interaction in perioperative chemotherapy for early breast cancer, Lancet, 2, 151, 10.1016/S0140-6736(87)92345-2

Kroemer, 2008, Tumor cell metabolism: cancer's Achilles' heel, Cancer Cell, 13, 472, 10.1016/j.ccr.2008.05.005

Fantin, 2006, Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance, Cancer Cell, 9, 425, 10.1016/j.ccr.2006.04.023

El-Mir, 2000, Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I, J Biol Chem, 275, 223, 10.1074/jbc.275.1.223

Ben Sahra, 2010, Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells, Cancer Res, 70, 2465, 10.1158/0008-5472.CAN-09-2782

Menendez, 2007, Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis, Nat Rev Cancer, 7, 763, 10.1038/nrc2222

Kuhajda, 2006, Fatty acid synthase and cancer: new application of an old pathway, Cancer Res, 66, 5977, 10.1158/0008-5472.CAN-05-4673

Xiang, 2004, AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms, Biochem Biophys Res Commun, 321, 161, 10.1016/j.bbrc.2004.06.133

Hadad, 2008, Targeting AMPK: a new therapeutic opportunity in breast cancer, Crit Rev Oncol Hematol, 67, 1, 10.1016/j.critrevonc.2008.01.007

Barba, 2009, Is it time to test metformin in breast cancer prevention trials? A reply to the authors, Cancer Epidemiol Biomarkers Prev, 18, 2565, 10.1158/1055-9965.EPI-09-0515

Hede, 2008, Doctors seek to prevent breast cancer recurrence by lowering insulin levels, J Natl Cancer Inst, 100, 530, 10.1093/jnci/djn119

Muti, 2009, Metformin, diet and breast cancer: an avenue for chemoprevention, Cell Cycle, 8, 2661, 10.4161/cc.8.16.9226

Yurekli, 2009, Is it the time for metformin to take place in adjuvant treatment of Her-2 positive breast cancer? Teaching new tricks to old dogs, Med Hypotheses, 73, 606, 10.1016/j.mehy.2009.05.027

Stambolic, 2009, Utility of metformin in breast cancer treatment, is neoangiogenesis a risk factor?, Breast Cancer Res Treat, 114, 387, 10.1007/s10549-008-0015-4

Oliveras-Ferraros, 2009, Genome-wide inhibitory impact of the AMPK activator metformin on [kinesins, tubulins, histones, auroras and polo-like kinases] M-phase cell cycle genes in human breast cancer cells, Cell Cycle, 8, 1633, 10.4161/cc.8.10.8406

Vazquez-Martin, 2009, The antidiabetic drug metformin: a pharmaceutical AMPK activator to overcome breast cancer resistance to HER2 inhibitors while decreasing risk of cardiomyopathy, Ann Oncol, 20, 592, 10.1093/annonc/mdn758

Wright, 2009, Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study, Cancer Causes Control, 20, 1617, 10.1007/s10552-009-9407-y

Jiralerspong, 2009, Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer, J Clin Oncol, 27, 3297, 10.1200/JCO.2009.19.6410

Li, 2009, Anti- diabetic therapies affect risk of pancreatic cancer, Gastroenterology, 137, 482, 10.1053/j.gastro.2009.04.013

Currie, 2009, The influence of glucose-lowering therapies on cancer risk in type 2 diabetes, Diabetologia, 52, 1766, 10.1007/s00125-009-1440-6

Rattan, 2009, Metformin attenuates ovarian cancer cell growth in an AMP- kinase dispensable manner, J Cell Mol Med