Metformin as an antitumor agent in cancer prevention and treatment

Journal of Diabetes

Volumn 3, Issue 4, 2011, Pages 320-327

  Li, Donghui ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

AMP activated protein kinase; Cancer; Chemoprevention; Diabetes; Metformin

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN; METFORMIN; PROTEIN KINASE LKB1; SULFONYLUREA;

ABERRANT CRYPT FOCUS; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER PREVENTION; CANCER RISK; CELL PROLIFERATION; CLINICAL TRIAL (TOPIC); COLON CANCER; DRUG MECHANISM; ENDOTHELIUM CELL; GLUCOSE METABOLISM; GLYCEMIC CONTROL; HUMAN; IMMUNOREGULATION; LIVER CARCINOMA; LUNG TUMOR; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS CANCER; PRIORITY JOURNAL; REVIEW; SHORT COURSE THERAPY;

ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS; HUMANS; METFORMIN; NEOPLASMS;

EID: 80053992117     PISSN: 17530393     EISSN: 17530407     Source Type: Journal    
DOI: 10.1111/j.1753-0407.2011.00119.x     Document Type: Review

References (65)

1. Giovannucci E, Harlan DM, Archer MC et al. Diabetes and cancer: a consensus report. CA Cancer J Clin. 2010; 60: 207-21.
2. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004; 8: 579-91.
3. Engelman JA, Cantley LC. Chemoprevention meets glucose control. Cancer Prev Res. 2010; 3: 1049-52.
4. Strack T, Strack T. Metformin: a review. Drugs Today. 2008; 44: 303-14.
5. Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006; 29: 254-8.
6. Monami M, Lamanna C, Balzi D et al. Sulphonylureas and cancer: a case-control study. Acta Diabetol. 2009; 46: 279-84.
7. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JMM. New users of metformin are at low risk of incident cancer. Diabetes Care. 2009; 32: 1620-5.
8. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009; 52: 1766-77.
9. Landman GW, Kleefstra N, van Hateren KJ et al. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010; 33: 322-6.
10. Yang YX, Hennessy S, Lewis JD. Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterology. 2004; 127: 1044-50.
11. Bodmer M, Meier C, Krahenbuhl S et al. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010; 33: 1304-8.
12. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009; 137: 482-8.
13. Hassan MM, Curley SA, Li D et al. Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer. 2010; 116: 1938-46.
14. Donadon V, Balbi M, Ghersetti M et al. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease. World J Gastroenterol. 2009; 15: 2506-11.
15. Wright JL, Stanford JL, Wright JL, Stanford JL. Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. Cancer Causes Control. 2009; 20: 1617-22.
16. Decensi A, Puntoni M, Goodwin P et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res. 2010; 3: 1451-61.
17. Hosono K, Endo H, Takahashi H et al. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev Res. 2010; 3: 1077-83.
18. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002; 137: 25-33.
19. Dilman VM, Berstein LM, Zabezhinski MA, Alexandrov VA, Bobrov JF, Pliss GB. Inhibition of DMBA-induced carcinogenesis by phenformin in the mammary gland of rats. Arch Geschwulstforsch. 1978; 48: 1-8.
20. Schneider MB, Matsuzaki H, Haorah J et al. Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology. 2001; 120: 1263-70.
21. Anisimov VN, Berstein LM, Egormin PA et al. Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp Gerontol. 2005; 40: 685-93.
22. Hou M, Venier N, Sugar L et al. Protective effect of metformin in CD1 mice placed on a high carbohydrate-high fat diet. Biochem Biophys Res Commun. 2010; 397: 537-42.
23. Phoenix KN, Vumbaca F, Fox MM et al. Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy. Breast Cancer Res Treat. 2010; 123: 333-44.
24. Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin prevents tobacco carcinogen-induced lung tumorigenesis. Cancer Prev Res. 2010; 3: 1066-76.
25. Balkwill F, Mantovani A. Inflammation and cancer: back to virchow? Lancet. 2001; 357: 539-45.
26. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420: 860-7.
27. Hundal RS, Inzucchi SE. Metformin: new understandings, new uses. Drugs. 2003; 63: 1879-94.
28. Ersoy C, Kiyici S, Budak F et al. The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients. Diabetes Res Clin Pract. 2008; 81: 56-60.
29. De Jager J, Kooy A, Lehert P et al. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2005; 257: 100-9.
30. Isoda K, Young JL, Zirlik A et al. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells. Arterioscler Thromb Vasc Biol. 2006; 26: 611-7.
31. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001; 37: 1344-50.
32. Aleisa AM, Al Rejaie SS, Bakheet SA et al. Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice. Mutat Res. 2007; 634: 93-100.
33. Giardiello FM, Brensinger JD, Tersmette AC et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000; 119: 1447-53.
34. Gwinn DM, Shackelford DB, Egan DF et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008; 30: 214-26.
35. Williams T, Brenman JE. LKB1 and AMPK in cell polarity and division. Trends Cell Biol. 2008; 18: 193-8.
36. Bensaad K, Vousden KH. p53: new roles in metabolism. Trends Cell Biol. 2007; 17: 286-91.
37. Tomimoto A, Endo H, Sugiyama M et al. Metformin suppresses intestinal polyp growth in ApcMin/+ mice. Cancer Sci. 2008; 99: 2136-41.
38. Hosono K, Endo H, Takahashi H et al. Metformin suppresses azoxymethane-induced colorectal aberrant crypt foci by activating AMP-activated protein kinase. Mol Carcinog. 2010; 49: 662-71.
39. Ben Sahra I, Laurent K, Loubat A et al. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 2008; 27: 3576-86.
40. Algire C, Zakikhani M, Blouin MJ et al. Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth. Endocr Relat Cancer. 2008; 15: 833-9.
41. Algire C, Amrein L, Zakikhani M, Panasci L, Pollak M. Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase. Endocr Relat Cancer. 2010; 17: 351-60.
42. Kisfalvi K, Eibl G, Sinnett-Smith J, Rozengurt E. Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Res. 2009; 69: 6539-45.
43. Rozengurt E, Sinnett-Smith J, Kisfalvi K, Rozengurt E, Sinnett-Smith J, Kisfalvi K. Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer. Clin Cancer Res. 2010; 16: 2505-11.
44. Alimova IN, Liu B, Fan Z et al. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle. 2009; 8: 909-15.
45. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 2006; 66: 10269-73.
46. Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 2007; 67: 10804-12.
47. Kalender A, Selvaraj A, Kim SY et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 2010; 11: 390-401.
48. Buzzai M, Jones RG, Amaravadi RK et al. Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res. 2007; 67: 6745-52.
49. Liu B, Fan Z, Edgerton SM et al. Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle. 2009; 8: 2031-40.
50. Pearce EL, Walsh MC, Cejas PJ et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 2009; 460: 103-7.
51. Prlic M, Bevan MJ. Immunology: a metabolic switch to memory. Nature. 2009; 460: 41-2.
52. Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA. The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle. 2009; 8: 88-96.
53. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009; 69: 7507-11.
54. Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res. 2010; 3: 1060-5.
55. Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. a consensus statement of the American diabetes association and the European association for the study of diabetes. Diabetes Care. 2009; 32: 193-203.
56. Jiralerspong S, Palla SL, Giordano SH et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009; 27: 3297-302.
57. Cazzaniga M, Bonanni B, Guerrieri-Gonzaga A et al. Is it time to test metformin in breast cancer clinical trials? Cancer Epidemiol Biomarkers Prev. 2009; 18: 701-5.
58. Goodwin PJ, Ligibel JA, Stambolic V. Metformin in breast cancer: time for action. J Clin Oncol. 2009; 27: 3271-3.
59. Martin-Castillo B, Dorca J, Vazquez-Martin A et al. 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. 2010; 21: 187-9.
60. Ben Sahra I, Le Marchand-Brustel Y, Tanti JF et al. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010; 9: 1092-9.
61. Phoenix KN, Vumbaca F, Claffey KP, Phoenix KN, Vumbaca F, Claffey KP. Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model. Breast Cancer Res Treat. 2009; 113: 101-11.
62. Hwang YP, Jeong HG, Hwang YP, Jeong HG. Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase C alpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1. Br J Pharmacol. 2010; 160: 1195-211.
63. Zakikhani M, Blouin MJ, Piura E, Pollak MN. Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. Breast Cancer Res Treat. 2010; 123: 271-9.
64. Sanli T, Rashid A, Liu C et al. Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells. Int J Radiat Oncol Biol Phys. 2010; 78: 221-9.
65. Ben Sahra I, Tanti JF, Bost F. The combination of metformin and 2-deoxyglucose inhibits autophagy and induces AMPK dependent apoptosis in prostate cancer cells. Autophagy. 2010; 65: 670-1.