Metformin: A candidate for the treatment of gynecological tumors based on drug repositioning (Review)
- Authors:
- Haruko Irie
- Kouji Banno
- Megumi Yanokura
- Miho Iida
- Masataka Adachi
- Kanako Nakamura
- Kiyoko Umene
- Yuya Nogami
- Kenta Masuda
- Yusuke Kobayashi
- Eiichiro Tominaga
- Daisuke Aoki
-
Affiliations: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160‑8582, Japan - Published online on: January 7, 2016 https://doi.org/10.3892/ol.2016.4075
- Pages: 1287-1293
This article is mentioned in:
Abstract
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Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R and Zinman B: Professional Practice Committee, American Diabetes Association; European Association for the Study of Diabetes: Management of hyperglycaemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 49:1711–1721. 2006. View Article : Google Scholar : PubMed/NCBI | |
Aljada A and Mousa SA: Metformin and neoplasia: Implications and indications. Pharmacol Ther. 133:108–115. 2012. View Article : Google Scholar : PubMed/NCBI | |
Soritau O, Tomuleasa C, Aldea M, Petrushev B, Susman S, Gheban D, Ioani H, Cosis A, Brie I, Irimie A, et al: Metformin plus temozolomide-based chemotherapy as adjuvant treatment for WHO grade III and IV malignant gliomas. J BUON. 16:282–289. 2011.PubMed/NCBI | |
Riedmaier Emami A, Fisel P, Nies AT, Schaeffeler E and Schwab P: Metformin and cancer: From the old medicine cabinet to pharmacological pitfalls and prospects. Trends Pharmacol Sci. 34:126–135. 2013. View Article : Google Scholar : PubMed/NCBI | |
Campagnoli C, Abbà C, Ambroggio S, Brucato T and Pasanisi P: Life-style and metformin for the prevention of endometrial pathology in postmenopausal women. Gynecol Endocrinol. 29:119–124. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ashburn TT and Thor KB: Drug repositioning: Identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 3:673–683. 2004. View Article : Google Scholar : PubMed/NCBI | |
Moiseeva O, Deschênes-Simard X, Pollak M and Ferbeyre G: Metformin, aging and cancer. Aging (Albany NY). 5:330–331. 2013.PubMed/NCBI | |
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R and Zinman B: American Diabetes Association; European Association for Study of Diabetes: 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. 32:193–203. 2009. View Article : Google Scholar : PubMed/NCBI | |
Bailey CJ: Biguanides and NIDDM. Diabetes Care. 15:755–772. 1992. View Article : Google Scholar : PubMed/NCBI | |
Bailey CJ and Turner RC: Metformin. N Engl J Med. 334:574–579. 1996. View Article : Google Scholar : PubMed/NCBI | |
Stumvoll M, Nurjhan N, Perriello G, Dailey G and Gerich JE: Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med. 333:550–554. 1995. View Article : Google Scholar : PubMed/NCBI | |
Morgan CL, Mukherjee J, Jenkins-Jones S, Holden SE and Currie CJ: Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: A retrospective, observational study. Diabetes Obes Metab. 16:957–962. 2014. View Article : Google Scholar : PubMed/NCBI | |
Chan NN, Brain HP and Feher MD: Metformin-associated lactic acidosis: A rare or very rare clinical entity? Diabet Med. 16:273–281. 1999. View Article : Google Scholar : PubMed/NCBI | |
Kilo C: Metformin: A safe and effective treatment in the management of NIDDM. Mo Med. 94:114–123. 1997.PubMed/NCBI | |
Vasisht KP, Chen SC, Peng Y and Bakris GL: Limitations of metformin use in patients with kidney disease: Are they warranted? Diabetes Obes Metab. 12:1079–1083. 2010. View Article : Google Scholar : PubMed/NCBI | |
Horlen C, Malone R, Bryant B, Dennis B, Carey T, Pignone M and Rothman R: Frequency of inappropriate metformin prescriptions. JAMA. 287:2504–2505. 2002. View Article : Google Scholar : PubMed/NCBI | |
Calabrese AT, Coley KC, DaPos SV, Swanson D and Rao RH: Evaluation of prescribing practices: Risk of lactic acidosis with metformin therapy. Arch Intern Med. 162:434–437. 2002. View Article : Google Scholar : PubMed/NCBI | |
Masoudi FA, Wang Y, Inzucchi SE, Setaro JF, Havranek EP, Foody JM and Krumholz HM: Metformin and thiazolidinedione use in Medicare patients with heart failure. JAMA. 290:81–85. 2003. View Article : Google Scholar : PubMed/NCBI | |
Stang M, Wysowski DK and Butler-Jones D: Incidence of lactic acidosis in metformin users. Diabetes Care. 22:925–927. 1999. View Article : Google Scholar : PubMed/NCBI | |
Saydah SH, Loria CM, Eberhardt MS and Brancati FL: Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol. 157:1092–1100. 2003. View Article : Google Scholar : PubMed/NCBI | |
Michels KB, Solomon CG, Hu FB, Rosner BA, Hankinson SE, Colditz GA and Manson JE: Nurses' Health Study: Type 2 diabetes and subsequent incidence of breast cancer in the Nurses' Health Study. Diabetes Care. 26:1752–1758. 2003. View Article : Google Scholar : PubMed/NCBI | |
Will JC, Galuska DA, Vinicor F and Calle EE: Colorectal cancer: Another complication of diabetes mellitus? Am J Epidemiol. 147:816–825. 1998. View Article : Google Scholar : PubMed/NCBI | |
Everhart J and Wright D: Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA. 273:1605–1609. 1995. View Article : Google Scholar : PubMed/NCBI | |
Gapstur SM, Gann PH, Colangelo LA, Barron-Simpson R, Kopp P, Dyer A and Liu K: Postload plasma glucose concentration and 27-year prostate cancer mortality (United States). Cancer Causes Control. 12:763–772. 2001. View Article : Google Scholar : PubMed/NCBI | |
Moore MA, Park CB and Tsuda H: Implications of the hyperinsulinaemia-diabetes-cancer link for preventive efforts. Eur J Cancer Prev. 7:89–107. 1998.PubMed/NCBI | |
Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR and Morris AD: Metformin and reduced risk of cancer in diabetic patients. BMJ. 330:1304–1305. 2005. View Article : Google Scholar : PubMed/NCBI | |
Bowker SL, Yasui Y, Veugelers P and Johnson JA: Glucose-lowering agents and cancer mortality rates in type 2 diabetes: Assessing effects of time-varying exposure. Diabetologia. 53:1631–1637. 2010. View Article : Google Scholar : PubMed/NCBI | |
Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD and Evans JM: New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes. Diabetes Care. 32:1620–1625. 2009. View Article : Google Scholar : PubMed/NCBI | |
Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M and Cantley LC: The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 310:1642–1646. 2005. View Article : Google Scholar : PubMed/NCBI | |
Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE and Shaw RJ: AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 30:214–226. 2008. View Article : Google Scholar : PubMed/NCBI | |
Inoki K, Li Y, Zhu T, Wu J and Guan KL: TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 4:648–657. 2002. View Article : Google Scholar : PubMed/NCBI | |
Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA and Bae-Jump VL: Metformin is a potent inhibitor of endometrial cancer cell proliferation - implications for a novel treatment strategy. Gynecol Oncol. 116:92–98. 2010. View Article : Google Scholar : PubMed/NCBI | |
Stephenne X, Foretz M, Taleux N, van der Zon GC, Sokal E, Hue L, Viollet B and Guigas P: Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status. Diabetologia. 54:3101–3110. 2011. View Article : Google Scholar : PubMed/NCBI | |
Gunton JE, Delhanty PJ, Takahashi S and Baxter RC: Metformin rapidly increases insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2. J Clin Endocrinol Metab. 88:1323–1332. 2003. View Article : Google Scholar : PubMed/NCBI | |
Sahra Ben I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y and Bost F: The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 27:3576–3586. 2008. View Article : Google Scholar : PubMed/NCBI | |
Calle EE, Rodriguez C, Walker-Thurmond K and Thun MJ: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 348:1625–1638. 2003. View Article : Google Scholar : PubMed/NCBI | |
Navaratnarajah R, Pillay OC and Hardiman P: Polycystic ovary syndrome and endometrial cancer. Semin Reprod Med. 26:62–71. 2008. View Article : Google Scholar : PubMed/NCBI | |
Dronavalli S and Ehrmann DA: Pharmacologic therapy of polycystic ovary syndrome. Clin Obstet Gynecol. 50:244–254. 2007. View Article : Google Scholar : PubMed/NCBI | |
Dumesic DA and Lobo RA: Cancer risk and PCOS. Steroids. 78:782–785. 2013. View Article : Google Scholar : PubMed/NCBI | |
Zhou C, Gehrig PA, Whang YE and Boggess JF: Rapamycin inhibits telomerase activity by decreasing the hTERT mRNA level in endometrial cancer cells. Mol Cancer Ther. 2:789–795. 2003.PubMed/NCBI | |
Xie Y, Wang YL, Yu L, Hu Q, Ji L, Zhang Y and Liao QP: Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. J Steroid Biochem Mol Biol. 126:113–120. 2011. View Article : Google Scholar : PubMed/NCBI | |
Tsuji K, Kisu I, Banno K, Yanokura M, Ueki A, Masuda K, Kobayashi Y, Yamagami W, Nomura H, Susumu N and Aoki D: Metformin: A possible drug for treatment of endometrial cancer. Open J Obstet Gynecol. 2:1–6. 2012. View Article : Google Scholar | |
Ko EM, Walter P, Jackson A, Clark L, Franasiak J, Bolac C, Havrilesky LJ, Secord AA, Moore DT, Gehrig PA and Bae-Jump V: Metformin is associated with improved survival in endometrial cancer. Gynecol Oncol. 132:438–442. 2014. View Article : Google Scholar : PubMed/NCBI | |
Wolf I, Sadetzki S, Catane R, Karasik A and Kaufman B: Diabetes mellitus and breast cancer. Lancet Oncol. 6:103–111. 2005. View Article : Google Scholar : PubMed/NCBI | |
Liu B, Fan Z, Edgerton SM, Deng XS, Alimova IN, Lind SE and Thor AD: Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle. 8:2031–2040. 2009. View Article : Google Scholar : PubMed/NCBI | |
Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE and Thor AD: Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle. 8:909–915. 2009. View Article : Google Scholar : PubMed/NCBI | |
Sachdev D, Singh R, Fujita-Yamaguchi Y and Yee D: Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: Implications for anti-insulin-like growth factor therapy in breast cancer. Cancer Res. 66:2391–2402. 2006. View Article : Google Scholar : PubMed/NCBI | |
Zakikhani M, Dowling R, Fantus IG, Sonenberg N and Pollak M: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66:10269–10273. 2006. View Article : Google Scholar : PubMed/NCBI | |
Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN and Gonzalez-Angulo AM: Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 27:3297–3302. 2009. View Article : Google Scholar : PubMed/NCBI | |
Kim J, Lim W, Kim EK, Kim MK, Paik NS, Jeong SS, Yoon JH, Park CH, Ahn SH, Kim LS, et al: Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR). BMC Cancer. 14:1702014. View Article : Google Scholar : PubMed/NCBI | |
Goodwin PJ, Stambolic V, Lemieux J, Chen BE, Parulekar WR, Gelmon KA, Hershman DL, Hobday TJ, Ligibel JA, Mayer IA, et al: Evaluation of metformin in early breast cancer: A modification of the traditional paradigm for clinical testing of anti-cancer agents. Breast Cancer Res Treat. 126:215–220. 2011. View Article : Google Scholar : PubMed/NCBI | |
Iliopoulos D, Hirsch HA and Struhl K: Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res. 71:3196–3201. 2011. View Article : Google Scholar : PubMed/NCBI | |
Ness RB, Grisso JA, Klapper J, Schlesselman JJ, Silberzweig S, Vergona R, Morgan M and Wheeler JE: Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives SHARE Study Group. Steroid Hormones and Reproductions. Am J Epidemiol. 152:233–241. 2000. View Article : Google Scholar : PubMed/NCBI | |
Gotlieb WH, Saumet J, Beauchamp MC, Gu J, Lau S, Pollak MN and Bruchim I: In vitro metformin anti-neoplastic activity in epithelial ovarian cancer. Gynecol Oncol. 110:246–250. 2008. View Article : Google Scholar : PubMed/NCBI | |
Bodmer M, Becker C, Meier C, Jick SS and Meier CR: Use of metformin and the risk of ovarian cancer: A case-control analysis. Gynecol Oncol. 123:200–204. 2011. View Article : Google Scholar : PubMed/NCBI | |
Home PD, Kahn SE, Jones NP, Noronha D, Beck-Nielsen H and Viberti G: ADOPT Study Group; RECORD Steering Committee: Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia. 53:1838–1845. 2010. View Article : Google Scholar : PubMed/NCBI | |
Zhang ZJ and Li S: The prognostic value of metformin for cancer patients with concurrent diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 16:707–710. 2014. View Article : Google Scholar : PubMed/NCBI | |
Kumar S, Meuter A, Thapa P, Langstraat C, Giri S, Chien J, Rattan R, Cliby W and Shridhar V: Metformin intake is associated with better survival in ovarian cancer: A case-control study. Cancer. 119:555–562. 2013. View Article : Google Scholar : PubMed/NCBI | |
Pollak M: Metformin and other biguanides in oncology: Advancing the research agenda. Cancer Prev Res (Phila). 3:1060–1065. 2010. View Article : Google Scholar : PubMed/NCBI | |
Fogarty S and Hardie DG: Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta. 1804:581–591. 2010. View Article : Google Scholar : PubMed/NCBI | |
Xiao X, He Q, Lu C, Werle KD, Zhao RX, Chen J, Davis BC, Cui R, Liang J and Xu ZX: Metformin impairs the growth of liver kinase B1-intact cervical cancer cells. Gynecol Oncol. 127:249–255. 2012. View Article : Google Scholar : PubMed/NCBI | |
Nevadunsky NS, Van Arsdale A, Strickler HD, Moadel A, Kaur G, Frimer M, Conroy E, Goldberg GL and Einstein P: Metformin use and endometrial cancer survival. Gynecol Oncol. 132:236–240. 2014. View Article : Google Scholar : PubMed/NCBI | |
He X, Esteva FJ, Ensor J, Hortobagyi GN, Lee MH and Yeung SC: Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann Oncol. 23:1771–1780. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hou G, Zhang S, Zhang X, Wang P, Hao X and Zhang J: Clinical pathological characteristics and prognostic analysis of 1,013 breast cancer patients with diabetes. Breast Cancer Res Treat. 137:807–816. 2013. View Article : Google Scholar : PubMed/NCBI | |
Peeters PJ, Bazelier MT, Vestergaard P, Leufkens HG, Schmidt MK, de Vries F and De Bruin ML: Use of metformin and survival of diabetic women with breast cancer. Curr Drug Saf. 8:357–363. 2013. View Article : Google Scholar : PubMed/NCBI | |
Xiao Y, Zhang S, Hou G, Zhang X, Hao X and Zhang J: Clinical pathological characteristics and prognostic analysis of diabetic women with luminal subtype breast cancer. Tumour Biol. 35:2035–2045. 2014. View Article : Google Scholar : PubMed/NCBI | |
Lega IC, Austin PC, Gruneir A, Goodwin PJ, Rochon PA and Lipscombe LL: Association between metformin therapy and mortality after breast cancer: A population-based study. Diabetes Care. 36:3018–3026. 2013. View Article : Google Scholar : PubMed/NCBI | |
Bayraktar S, Hernadez-Aya LF, Lei X, Meric-Bernstam F, Litton JK, Hsu L, Hortobagyi GN and Gonzalez-Angulo AM: Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer. 118:1202–1211. 2012. View Article : Google Scholar : PubMed/NCBI | |
Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA and Morgan CL: Mortality after incident cancer in people with and without type 2 diabetes: Impact of metformin on survival. Diabetes Care. 35:299–304. 2012. View Article : Google Scholar : PubMed/NCBI | |
Romero IL, McCormick A, McEwen KA, Park S, Karrison T, Yamada SD, Pannain S and Lengyel E: Relationship of type II diabetes and metformin use to ovarian cancer progression, survival, and chemosensitivity. Obstet Gynecol. 119:61–67. 2012. View Article : Google Scholar : PubMed/NCBI |