Potential anti-cancer features of metformin
DOI:
https://doi.org/10.12775/JEHS.2023.13.01.022Keywords
metformin, cancer, AMPK, type 2 diabetes mellitus, prevention, treatmentAbstract
INTRODUCTION AND PURPOSE:
Metformin is one of the most frequently prescribed medications in the whole world. This lipophilic biguanide is widely used as a first-line medicine for patients suffering from type 2 diabetes mellitus because of its high effectiveness in monotherapy, and in connection with other antidiabetic drugs. Glucose-lowering properties of metformin were initially used only in the therapy of type 2 diabetes mellitus, but some data indicate that these properties might state an alternative in the prevention or treatment of some cancers both among diabetic and non-diabetic patients.
STATE OF KNOWLEDGE:
Metformin molecular mechanisms of action were thoroughly investigated, differentiated, and described, but in the context of the glucose-lowering effect. As a multiway drug, used mainly in diseases characterized by an increased level of glucose in the blood, numerous medical trials were conducted to find other treating properties of metformin. Recently, a few reports presented the potential connection between using metformin in the prevention and treatment of neoplasms in the same mechanisms. The scientists analyzed the influence of metformin’s action on various cancers and drew conclusions. The research on potential anti-cancer features of metformin was conducted for a relatively short period and still presents a challenge to scientists.
CONCLUSIONS:
The aim of this review is to gather current knowledge and present the latest discoveries about potential anti-cancer features of metformin. We discuss the potential underlying molecular mechanisms of metformin’s action in the human body and indicate the connection between the prevention and treatment of neoplasms. Additionally, we point out the exact cancers in which metformin might play a significant role.
References
„Umieralność w 2021 roku. Zgony według przyczyn – dane wstępne.”
https://stat.gov.pl/download/gfx/portalinformacyjny/pl/defaultaktualnosci/5746/10/3/1/umieralnosc_i_zgony_wedlug_przyczyn_w_2021_roku.pdf [data dostępu: 28.10.2022].
Potrykowska A. Strzelecki Z. Szymborski J. Witkowski J. & Polska. (2014). Zachorowalność i umieralność na nowotwory a sytuacja demograficzna polski. Rządowa Rada Ludnościowa, s. 149-151. ISBN 978-83-7027-573-0, OCLC: 903342972.
Harding JL, Shaw JE, Peeters A, Cartensen B, Magliano DJ. Cancer risk among people with type 1 and type 2 diabetes: disentangling true associations, detection bias, and reverse causation. Diabetes Care. 2015 Feb;38(2):264-70. doi: 10.2337/dc14-1996. Epub 2014 Dec 8. Erratum in: Diabetes Care. 2015 Apr;38(4):734-5. PMID: 25488912.
Fischer János & Ganellin C. R. (2010). Analogue-based drug discovery ii. Wiley-VCH, p.47-49. ISBN: 978-3-527-63003-5, OCLC: 663460979. doi: 10.1002/9783527630035.
Franek E. Walicka M. & Wydawnictwo Lekarskie PZWL. (2018). Leczenie cukrzycy w praktyce klinicznej : dla lekarzy różnych specjalności. t. 1. PZWL Wydawnictwo Lekarskie, s. 6-8. ISBN 978-83-200-5592-4, OCLC: 1051257803.
Bailey CJ. Metformin: historical overview. Diabetologia. 2017 Sep;60(9):1566-1576. doi: 10.1007/s00125-017-4318-z. Epub 2017 Aug 3. PMID: 28776081.
Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005 Jun 4;330(7503):1304-5. doi: 10.1136/bmj.38415.708634.F7. Epub 2005 Apr 22. PMID: 15849206; PMCID: PMC558205.
Lv Z, Guo Y. Metformin and Its Benefits for Various Diseases. Front Endocrinol (Lausanne). 2020 Apr 16;11:191. doi: 10.3389/fendo.2020.00191. PMID: 32425881; PMCID: PMC7212476.
Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B, Gandini S. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010 Nov;3(11):1451-61. doi: 10.1158/1940-6207.CAPR-10-0157. Epub 2010 Oct 12. PMID: 20947488.
LaMoia TE, Shulman GI. Cellular and Molecular Mechanisms of Metformin Action. Endocr Rev. 2021 Jan 28;42(1):77-96. doi: 10.1210/endrev/bnaa023. PMID: 32897388; PMCID: PMC7846086.
Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012 Mar;122(6):253-70. doi: 10.1042/CS20110386. PMID: 22117616; PMCID: PMC3398862.
Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, Vigneri R. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008 Feb;114(1):23-37. doi: 10.1080/13813450801969715. PMID: 18465356.
Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK, Gans RO, de Vries EG. Metformin: taking away the candy for cancer? Eur J Cancer. 2010 Sep;46(13):2369-80. doi: 10.1016/j.ejca.2010.06.012. Epub 2010 Jul 23. PMID: 20656475.
Choi YK, Park KG. Metabolic roles of AMPK and metformin in cancer cells. Mol Cells. 2013 Oct;36(4):279-87. doi: 10.1007/s10059-013-0169-8. Epub 2013 Jun 19. PMID: 23794020; PMCID: PMC3887985.
Ning J, Clemmons DR. AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation. Mol Endocrinol. 2010 Jun;24(6):1218-29. doi: 10.1210/me.2009-0474. Epub 2010 Apr 2. PMID: 20363874; PMCID: PMC2875806.
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 May 1;16(9):2505-11. doi: 10.1158/1078-0432.CCR-09-2229. Epub 2010 Apr 13. PMID: 20388847; PMCID: PMC2862089.
Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. doi: 10.1172/JCI29069. Erratum in: J Clin Invest. 2006 Aug;116(8):2308. PMID: 16823477; PMCID: PMC1483173.
Dallaglio K, Bruno A, Cantelmo AR, Esposito AI, Ruggiero L, Orecchioni S, Calleri A, Bertolini F, Pfeffer U, Noonan DM, Albini A. Paradoxic effects of metformin on endothelial cells and angiogenesis. Carcinogenesis. 2014 May;35(5):1055-66. doi: 10.1093/carcin/bgu001. Epub 2014 Jan 13. PMID: 24419232; PMCID: PMC4004203.
Podhorecka M, Ibanez B, Dmoszyńska A. Metformin - its potential anti-cancer and anti-aging effects. Postepy Hig Med Dosw (Online). 2017 Mar 2;71(0):170-175. doi: 10.5604/01.3001.0010.3801. PMID: 28258677.
Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):251-62. doi: 10.1038/nrm3311. PMID: 22436748; PMCID: PMC5726489.
Brandt U. Energy converting NADH:quinone oxidoreductase (complex I). Annu Rev Biochem. 2006;75:69-92. doi: 10.1146/annurev.biochem.75.103004.142539. PMID: 16756485.
Lin HV, Accili D. Hormonal regulation of hepatic glucose production in health and disease. Cell Metab. 2011 Jul 6;14(1):9-19. doi: 10.1016/j.cmet.2011.06.003. PMID: 21723500; PMCID: PMC3131084.
Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T, Chen ZP, O'Neill HM, Ford RJ, Palanivel R, O'Brien M, Hardie DG, Macaulay SL, Schertzer JD, Dyck JR, van Denderen BJ, Kemp BE, Steinberg GR. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med. 2013 Dec;19(12):1649-54. doi: 10.1038/nm.3372. Epub 2013 Nov 3. PMID: 24185692; PMCID: PMC4965268.
Carlson CA, Kim KH. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. Arch Biochem Biophys. 1974 Oct;164(2):478-89. doi: 10.1016/0003-9861(74)90058-7. PMID: 4156633.
Xiang X, Saha AK, Wen R, Ruderman NB, Luo Z. AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem Biophys Res Commun. 2004 Aug 13;321(1):161-7. doi: 10.1016/j.bbrc.2004.06.133. PMID: 15358229.
Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012 Oct 26;48(2):158-67. doi: 10.1016/j.molcel.2012.09.025. PMID: 23102266; PMCID: PMC3484374.
Wong HS, Dighe PA, Mezera V, Monternier PA, Brand MD. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem. 2017 Oct 13;292(41):16804-16809. doi: 10.1074/jbc.R117.789271. Epub 2017 Aug 24. PMID: 28842493; PMCID: PMC5641882.
Batandier C, Guigas B, Detaille D, El-Mir MY, Fontaine E, Rigoulet M, Leverve XM. The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin. J Bioenerg Biomembr. 2006 Feb;38(1):33-42. doi: 10.1007/s10863-006-9003-8. PMID: 16732470.
Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y, Bost F. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 2008 Jun 5;27(25):3576-86. doi: 10.1038/sj.onc.1211024. Epub 2008 Jan 21. PMID: 18212742.
Malki A, Youssef A. Antidiabetic drug metformin induces apoptosis in human MCF breast cancer via targeting ERK signaling. Oncol Res. 2011;19(6):275-85. doi: 10.3727/096504011x13021877989838. PMID: 21776823.
Demir U, Koehler A, Schneider R, Schweiger S, Klocker H. Metformin anti-tumor effect via disruption of the MID1 translational regulator complex and AR downregulation in prostate cancer cells. BMC Cancer. 2014 Jan 31;14:52. doi: 10.1186/1471-2407-14-52. PMID: 24484909; PMCID: PMC3929757.
Janku F, McConkey DJ, Hong DS, Kurzrock R. Autophagy as a target for anticancer therapy. Nat Rev Clin Oncol. 2011 May 17;8(9):528-39. doi: 10.1038/nrclinonc.2011.71. PMID: 21587219.
Sui X, Chen R, Wang Z, Huang Z, Kong N, Zhang M, Han W, Lou F, Yang J, Zhang Q, Wang X, He C, Pan H. Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death Dis. 2013 Oct 10;4(10):e838. doi: 10.1038/cddis.2013.350. PMID: 24113172; PMCID: PMC3824660.
Brodowska K, Theodoropoulou S, Meyer Zu Hörste M, Paschalis EI, Takeuchi K, Scott G, Ramsey DJ, Kiernan E, Hoang M, Cichy J, Miller JW, Gragoudas ES, Vavvas DG. Effects of metformin on retinoblastoma growth in vitro and in vivo. Int J Oncol. 2014 Dec;45(6):2311-24. doi: 10.3892/ijo.2014.2650. Epub 2014 Sep 11. PMID: 25215935; PMCID: PMC4215581.
Xiao X, He Q, Lu C, Werle KD, Zhao RX, Chen J, Davis BC, Cui R, Liang J, Xu ZX. Metformin impairs the growth of liver kinase B1-intact cervical cancer cells. Gynecol Oncol. 2012 Oct;127(1):249-55. doi: 10.1016/j.ygyno.2012.06.032. Epub 2012 Jun 24. PMID: 22735790; PMCID: PMC3432698.
Takahashi A, Kimura F, Yamanaka A, Takebayashi A, Kita N, Takahashi K, Murakami T. Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis. Cancer Cell Int. 2014 Jun 16;14:53. doi: 10.1186/1475-2867-14-53. PMID: 24966801; PMCID: PMC4070401.
Tomic T, Botton T, Cerezo M, Robert G, Luciano F, Puissant A, Gounon P, Allegra M, Bertolotto C, Bereder JM, Tartare-Deckert S, Bahadoran P, Auberger P, Ballotti R, Rocchi S. Metformin inhibits melanoma development through autophagy and apoptosis mechanisms. Cell Death Dis. 2011 Sep 1;2(9):e199. doi: 10.1038/cddis.2011.86. PMID: 21881601; PMCID: PMC3186904.
Shi WY, Xiao D, Wang L, Dong LH, Yan ZX, Shen ZX, Chen SJ, Chen Y, Zhao WL. Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis. 2012 Mar 1;3(3):e275. doi: 10.1038/cddis.2012.13. PMID: 22378068; PMCID: PMC3317343.
Yoshida S, Hong S, Suzuki T, Nada S, Mannan AM, Wang J, Okada M, Guan KL, Inoki K. Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway. J Biol Chem. 2011 Sep 16;286(37):32651-60. doi: 10.1074/jbc.M111.238014. Epub 2011 Jul 22. PMID: 21784859; PMCID: PMC3173157.
Hall MN. mTOR-what does it do? Transplant Proc. 2008 Dec;40(10 Suppl):S5-8. doi: 10.1016/j.transproceed.2008.10.009. PMID: 19100909.
Yoon MS. The Role of Mammalian Target of Rapamycin (mTOR) in Insulin Signaling. Nutrients. 2017 Oct 27;9(11):1176. doi: 10.3390/nu9111176. PMID: 29077002; PMCID: PMC5707648.
Davila D, Connolly NM, Bonner H, Weisová P, Dussmann H, Concannon CG, Huber HJ, Prehn JH. Two-step activation of FOXO3 by AMPK generates a coherent feed-forward loop determining excitotoxic cell fate. Cell Death Differ. 2012 Oct;19(10):1677-88. doi: 10.1038/cdd.2012.49. Epub 2012 Apr 27. PMID: 22539004; PMCID: PMC3438498.
Kalender A, Selvaraj A, Kim SY, Gulati P, Brûlé S, Viollet B, Kemp BE, Bardeesy N, Dennis P, Schlager JJ, Marette A, Kozma SC, Thomas G. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 2010 May 5;11(5):390-401. doi: 10.1016/j.cmet.2010.03.014. PMID: 20444419; PMCID: PMC3081779.
Efeyan A, Zoncu R, Sabatini DM. Amino acids and mTORC1: from lysosomes to disease. Trends Mol Med. 2012 Sep;18(9):524-33. doi: 10.1016/j.molmed.2012.05.007. Epub 2012 Jun 28. PMID: 22749019; PMCID: PMC3432651.
Corominas-Faja B, Quirantes-Piné R, Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Martin-Castillo B, Micol V, Joven J, Segura-Carretero A, Menendez JA. Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs. Aging (Albany NY). 2012 Jul;4(7):480-98. doi: 10.18632/aging.100472. PMID: 22837425; PMCID: PMC3433934.
Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007 Mar-Apr;21(2):118-23. doi: 10.1016/j.jdiacomp.2005.10.005. PMID: 17331860.
Cabreiro F, Au C, Leung KY, Vergara-Irigaray N, Cochemé HM, Noori T, Weinkove D, Schuster E, Greene ND, Gems D. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell. 2013 Mar 28;153(1):228-39. doi: 10.1016/j.cell.2013.02.035. PMID: 23540700; PMCID: PMC3898468.
Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006 Oct 30;25(51):6680-4. doi: 10.1038/sj.onc.1209954. PMID: 17072321.
Kim HG, Hien TT, Han EH, Hwang YP, Choi JH, Kang KW, Kwon KI, Kim BH, Kim SK, Song GY, Jeong TC, Jeong HG. Metformin inhibits P-glycoprotein expression via the NF-κB pathway and CRE transcriptional activity through AMPK activation. Br J Pharmacol. 2011 Mar;162(5):1096-108. doi: 10.1111/j.1476-5381.2010.01101.x. PMID: 21054339; PMCID: PMC3051382.
Daugan M, Dufaÿ Wojcicki A, d'Hayer B, Boudy V. Metformin: An anti-diabetic drug to fight cancer. Pharmacol Res. 2016 Nov;113(Pt A):675-685. doi: 10.1016/j.phrs.2016.10.006. Epub 2016 Oct 5. PMID: 27720766.
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):1-8. PMID: 418748.
Dilman VM, Berstein LM, Yevtushenko TP, Tsyrlina YV, Ostroumova MN, Bobrov YuF, Revskoy SYu, Kovalenko IG, Simonov NN. Preliminary evidence on metabolic rehabilitation of cancer patients. Arch Geschwulstforsch. 1988;58(3):175-83. PMID: 3415435.
Lee JH, Jeon SM, Hong SP, Cheon JH, Kim TI, Kim WH. Metformin use is associated with a decreased incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. Dig Liver Dis. 2012 Dec;44(12):1042-7. doi: 10.1016/j.dld.2012.06.007. Epub 2012 Jul 11. PMID: 22789400.
Spillane S, Bennett K, Sharp L, Barron TI. A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2013 Aug;22(8):1364-73. doi: 10.1158/1055-9965.EPI-13-0347. Epub 2013 Jun 10. PMID: 23753040.
Fransgaard T, Thygesen LC, Gögenur I. Metformin Increases Overall Survival in Patients with Diabetes Undergoing Surgery for Colorectal Cancer. Ann Surg Oncol. 2016 May;23(5):1569-75. doi: 10.1245/s10434-015-5028-8. Epub 2015 Dec 29. PMID: 26714936.
Jones GR, Molloy MP. Metformin, Microbiome and Protection Against Colorectal Cancer. Dig Dis Sci. 2021 May;66(5):1409-1414. doi: 10.1007/s10620-020-06390-4. Epub 2020 Jun 12. PMID: 32533543.
Yang T, Yang Y, Liu S. Association between Metformin Therapy and Breast Cancer Incidence and Mortality: Evidence from a Meta-Analysis. J Breast Cancer. 2015 Sep;18(3):264-70. doi: 10.4048/jbc.2015.18.3.264. Epub 2015 Sep 24. PMID: 26472977; PMCID: PMC4600691.
Lee J, Yesilkanal AE, Wynne JP, Frankenberger C, Liu J, Yan J, Elbaz M, Rabe DC, Rustandy FD, Tiwari P, Grossman EA, Hart PC, Kang C, Sanderson SM, Andrade J, Nomura DK, Bonini MG, Locasale JW, Rosner MR. Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism. Nature. 2019 Apr;568(7751):254-258. doi: 10.1038/s41586-019-1005-x. Epub 2019 Mar 6. PMID: 30842661; PMCID: PMC6698916.
Vallianou NG, Evangelopoulos A, Kazazis C. Metformin and cancer. Rev Diabet Stud. 2013 Winter;10(4):228-35. doi: 10.1900/RDS.2013.10.228. Epub 2014 Feb 10. PMID: 24841876; PMCID: PMC4160009.
Ma S, Zheng Y, Xiao Y, Zhou P, Tan H. Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients. Medicine (Baltimore). 2017 May;96(19):e6888. doi: 10.1097/MD.0000000000006888. PMID: 28489794; PMCID: PMC5428628.
Ma SJ, Zheng YX, Zhou PC, Xiao YN, Tan HZ. Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis. Oncotarget. 2016 Oct 4;7(40):66202-66211. doi: 10.18632/oncotarget.11033. PMID: 27494848; PMCID: PMC5323227.
Lee YS, Kim YS, Lee SY, Kim GH, Kim BJ, Lee SH, Lee KU, Kim GS, Kim SW, Koh JM. AMP kinase acts as a negative regulator of RANKL in the differentiation of osteoclasts. Bone. 2010 Nov;47(5):926-37. doi: 10.1016/j.bone.2010.08.001. Epub 2010 Aug 7. PMID: 20696287.
Chen YH, Wang PH, Chen PN, Yang SF, Hsiao YH. Molecular and Cellular Mechanisms of Metformin in Cervical Cancer. Cancers (Basel). 2021 May 22;13(11):2545. doi: 10.3390/cancers13112545. PMID: 34067321; PMCID: PMC8196882.
Ko EM, Walter P, Jackson A, Clark L, Franasiak J, Bolac C, Havrilesky LJ, Secord AA, Moore DT, Gehrig PA, Bae-Jump V. Metformin is associated with improved survival in endometrial cancer. Gynecol Oncol. 2014 Feb;132(2):438-42. doi: 10.1016/j.ygyno.2013.11.021. Epub 2013 Nov 22. PMID: 24269517.
Nevadunsky NS, Van Arsdale A, Strickler HD, Moadel A, Kaur G, Frimer M, Conroy E, Goldberg GL, Einstein MH. Metformin use and endometrial cancer survival. Gynecol Oncol. 2014 Jan;132(1):236-40. doi: 10.1016/j.ygyno.2013.10.026. Epub 2013 Nov 2. PMID: 24189334; PMCID: PMC3904540.
King MC, Marks JH, Mandell JB; New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003 Oct 24;302(5645):643-6. doi: 10.1126/science.1088759. PMID: 14576434.
Urpilainen E, Puistola U, Boussios S, Karihtala P. Metformin and ovarian cancer: the evidence. Ann Transl Med. 2020 Dec;8(24):1711. doi: 10.21037/atm-20-1060. PMID: 33490223; PMCID: PMC7812201.
Zheng Y, Zhu J, Zhang H, Liu Y, Sun H. Metformin inhibits ovarian cancer growth and migration in vitro and in vivo by enhancing cisplatin cytotoxicity. Am J Transl Res. 2018 Oct 15;10(10):3086-3098. PMID: 30416652; PMCID: PMC6220222.
Li Y, Hu L, Xia Q, Yuan Y, Mi Y. The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis. Int Urol Nephrol. 2017 Jun;49(6):975-981. doi: 10.1007/s11255-017-1548-4. Epub 2017 Mar 7. PMID: 28271326; PMCID: PMC5443884.
Xiao K, Liu F, Liu J, Xu J, Wu Q, Li X. The effect of metformin on lung cancer risk and survival in patients with type 2 diabetes mellitus: A meta-analysis. J Clin Pharm Ther. 2020 Aug;45(4):783-792. doi: 10.1111/jcpt.13167. Epub 2020 May 14. PMID: 32406122.
Zhong S, Wu Y, Yan X, Tang J, Zhao J. Metformin use and survival of lung cancer patients: Meta-analysis findings. Indian J Cancer. 2017 Jan-Mar;54(1):63-67. doi: 10.4103/0019-509X.219582. PMID: 29199666.
Koo HY, Jeong SM, Cho MH, Chun S, Shin DW, Park J. Population-wide impacts of aspirin, statins, and metformin use on prostate cancer incidence and mortality. Sci Rep. 2021 Aug 9;11(1):16171. doi: 10.1038/s41598-021-95764-3. PMID: 34373584; PMCID: PMC8352896.
Tomic T, Botton T, Cerezo M, Robert G, Luciano F, Puissant A, Gounon P, Allegra M, Bertolotto C, Bereder JM, Tartare-Deckert S, Bahadoran P, Auberger P, Ballotti R, Rocchi S. Metformin inhibits melanoma development through autophagy and apoptosis mechanisms. Cell Death Dis. 2011 Sep 1;2(9):e199. doi: 10.1038/cddis.2011.86. PMID: 21881601; PMCID: PMC3186904.
Niehr F, von Euw E, Attar N, Guo D, Matsunaga D, Sazegar H, Ng C, Glaspy JA, Recio JA, Lo RS, Mischel PS, Comin-Anduix B, Ribas A. Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations. J Transl Med. 2011 May 24;9:76. doi: 10.1186/1479-5876-9-76. PMID: 21609436; PMCID: PMC3152784.
Janjetovic K, Harhaji-Trajkovic L, Misirkic-Marjanovic M, Vucicevic L, Stevanovic D, Zogovic N, Sumarac-Dumanovic M, Micic D, Trajkovic V. In vitro and in vivo anti-melanoma action of metformin. Eur J Pharmacol. 2011 Oct 15;668(3):373-82. doi: 10.1016/j.ejphar.2011.07.004. Epub 2011 Jul 27. PMID: 21806981.
Bruno S, Ledda B, Tenca C, Ravera S, Orengo AM, Mazzarello AN, Pesenti E, Casciaro S, Racchi O, Ghiotto F, Marini C, Sambuceti G, DeCensi A, Fais F. Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells. Oncotarget. 2015 Sep 8;6(26):22624-40. doi: 10.18632/oncotarget.4168. PMID: 26265439; PMCID: PMC4673187.
Shi WY, Xiao D, Wang L, Dong LH, Yan ZX, Shen ZX, Chen SJ, Chen Y, Zhao WL. Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis. 2012 Mar 1;3(3):e275. doi: 10.1038/cddis.2012.13. PMID: 22378068; PMCID: PMC3317343.
Jagannathan S, Abdel-Malek MA, Malek E, Vad N, Latif T, Anderson KC, Driscoll JJ. Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib. Leukemia. 2015 Nov;29(11):2184-91. doi: 10.1038/leu.2015.157. Epub 2015 Jun 25. PMID: 26108695; PMCID: PMC4635337.
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