Metformin enhanced in vitro radiosensitivity associates with G2/M cell cycle arrest and elevated adenosine-5’-monophosphate-activated protein kinase levels in glioblastoma
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Warburg O, Wind F, Negelein E. The metabolism of tumors in the Body. J Gen Physiol 1927; 8: 519-30.10.1085/jgp.8.6.519WarburgOWindFNegeleinE.The metabolism of tumors in the BodyJ Gen Physiol1927851930Open DOISearch in Google Scholar
Warburg O. On the origin of cancer cells. Science 1956; 123: 309-14.10.1126/science.123.3191.30913298683WarburgO.On the origin of cancer cellsScience195612330914Open DOISearch in Google Scholar
Adeberg S, Bernhardt D, Harrabi SB, Bostel T, Mohr A, Koelsche C, et al. Metformin influences progression in diabetic glioblastoma patients. Strahlentherapie Onkol 2015; 191: 928-35. 10.1007/s00066-015-0884-5AdebergSBernhardtDHarrabiSBBostelTMohrAKoelscheCMetformin influences progression in diabetic glioblastoma patientsStrahlentherapie Onkol20151919283510.1007/s00066-015-0884-5Open DOISearch in Google Scholar
Goodarzi MO, Bryer-Ash M. Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents. Diabetes ObesMetab 2005; 7: 654-65. 10.1111/j.1463-1326.2004.00448GoodarziMOBryer-AshM.Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agentsDiabetes ObesMetab200576546510.1111/j.1463-1326.2004.00448Open DOISearch in Google Scholar
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001; 108: 1167-74. 10.1172/JCI1350511602624ZhouGMyersRLiYChenYShenXFenyk-MelodyJRole of AMP-activated protein kinase in mechanism of metformin actionJ Clin Invest200110811677410.1172/JCI13505Open DOISearch in Google Scholar
Sesen J, Dahan P, Scotland SJ, Saland E, Dang VT, Lemarie A, et al. Metformin inhibits growth of human glioblastoma cells and enhances therapeutic response. PLoS One 2015; 10: e0123721. 10.1371/journal.pone.0123721SesenJDahanPScotlandSJSalandEDangVTLemarieAMetformin inhibits growth of human glioblastoma cells and enhances therapeutic responsePLoS One201510e10.1371/journal.pone.0123721Open DOISearch in Google Scholar
Zannella VE, Cojocari D, Hilgendorf S, Vellanki RN, Chung S, Wouters BG, et al. AMPK regulates metabolism and survival in response to ionizing radiation. Radiother Oncol 2011; 99: 293-9. 10.1016/j.radonc.2011.05.04921715037ZannellaVECojocariDHilgendorfSVellankiRNChungSWoutersBGAMPK regulates metabolism and survival in response to ionizing radiationRadiother Oncol201199293910.1016/j.radonc.2011.05.049Open DOISearch in Google Scholar
Steinberg GR, Kemp BE. AMPK in health and disease. Physiol Review 2009; 89: 1025-78. 10.1152/physrev.00011.2008SteinbergGRKempBE.AMPK in health and diseasePhysiol Review20098910257810.1152/physrev.00011.2008Open DOISearch in Google Scholar
Jang T, Calaoagan JM, Kwon E, Samuelsson S, Recht L, Laderoute KR. 5'-AMP-activated protein kinase activity is elevated early during primary brain tumor development in the rat. Int J Cancer 2011; 128: 2230-9. 10.1002/ijc.2555820635388JangTCalaoaganJMKwonESamuelssonSRechtLLaderouteKR.5’-AMP-activated protein kinase activity is elevated early during primary brain tumor development in the ratInt J Cancer20111282230910.1002/ijc.25558Open DOISearch in Google Scholar
Park HU, Suy S, Danner M, Dailey V, Zhang Y, Li H, et al. AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther 2009; 8: 733-41. 10.1158/1535-716319372545ParkHUSuySDannerMDaileyVZhangYLiHAMP-activated protein kinase promotes human prostate cancer cell growth and survivalMol Cancer Ther200987334110.1158/1535-7163Open DOISearch in Google Scholar
Sanli T, Rashid A, Liu C, Harding S, Bristow RG, Cutz JC, et al. Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells. Int J Radiat Oncol Bool Phys 2010; 78: 221-9. 10.1016/j.ijrobpSanliTRashidALiuCHardingSBristowRGCutzJCIonizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cellsInt J Radiat Oncol Bool Phys201078221910.1016/j.ijrobpOpen DOISearch in Google Scholar
Zhang WB, Wang Z, Shu F, Jin YH, Liu HY, Wang QJ, et al. Activation of AMP-activated protein kinase by temozolomide contributes to apoptosis in glioblastoma cells via p53 activation and mTORC1 inhibition. J Biol Chem 2010; 285: 40461-71. 10.1074/jbc.M110.16404620880848ZhangWBWangZShuFJinYHLiuHYWangQJActivation of AMP-activated protein kinase by temozolomide contributes to apoptosis in glioblastoma cells via p53 activation and mTORC1 inhibitionJ Biol Chem2010285404617110.1074/jbc.M110.164046Open DOISearch in Google Scholar
Bischof M, Abdollahi A, Gong P, Stoffregen C, Lipson KE, Debus JU, et al. Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cells. Int J Radiat OncolBiolPhys 2004; 60: 1220-32. 10.1016/j.ijrobpBischofMAbdollahiAGongPStoffregenCLipsonKEDebusJUTriple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cellsInt J Radiat Oncol BiolPhys20046012203210.1016/j.ijrobpOpen DOISearch in Google Scholar
Combs SE, Bohl J, Elsasser T, Weber KJ, Schulz-Ertner D, Debus J, et al. Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines. Int J Radiat Biol 2009; 85: 126-37. 10.1080/0955300080264115119280465CombsSEBohlJElsasserTWeberKJSchulz-ErtnerDDebusJRadiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell linesInt J Radiat Biol2009851263710.1080/09553000802641151Open DOISearch in Google Scholar
Liu X, Chhipa RR, Pooya S, Wortman M, Yachyshin S, Chow LM, et al. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc Natl Acad Sci U S A 2014; 111: E435-44. 10.1073/pnas.131112111124474794LiuXChhipaRRPooyaSWortmanMYachyshinSChowLMDiscrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPKProc Natl Acad Sci U S A2014111E4354410.1073/pnas.1311121111Open DOISearch in Google Scholar
Wurth R, Pattarozzi A, Gatti M, Bajetto A, Corsaro A, Parodi A, et al. Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt. Cell Cycle 2013; 12: 145-56. 10.4161/cc.2305023255107WurthRPattarozziAGattiMBajettoACorsaroAParodiAMetformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of AktCell Cycle2013121455610.4161/cc.23050Open DOISearch in Google Scholar
Janjetovic K, Harhaji-Trajkovic L, Misirkic-Marjanovic M, Vucicevic L, Stevanovic D, Zogovic N, et al. In vitro and in vivo anti-melanoma action of metformin. Eur J Pharmacol 2011; 668: 373-82. 10.1016/j.ejphar21806981JanjetovicKHarhaji-TrajkovicLMisirkic-MarjanovicMVucicevicLStevanovicDZogovicNIn vitro and in vivo anti-melanoma action of metforminEur J Pharmacol20116683738210.1016/j.ejpharOpen DOISearch in Google Scholar
Scotland S, Saland E, Skuli N, de Toni F, Boutzen H, Micklow E, et al. Mitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cells. Leukemia 2013; 27: 212938. 10.1038/leuScotlandSSalandESkuliNde ToniFBoutzenHMicklowEMitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cellsLeukemia20132721293810.1038/leuOpen DOISearch in Google Scholar
Feng Y, Ke C, Tang Q, Dong H, Zheng X, Lin W, et al. Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by down-regulating Stat3 signaling. Cell Death Dis 2014; 5: e1088. 10.1038/cddisFengYKeCTangQDongHZhengXLinWMetformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by down-regulating Stat3 signalingCell Death Dis20145e10.1038/cddisOpen DOISearch in Google Scholar
Tomic T, Botton T, Cerezo M, Robert G, Luciano F, Puissant A, et al. Metformin inhibits melanoma development through autophagy and apoptosis mechanisms. Cell Death Dis 2011; 2: e199. 10.1038/cddisTomicTBottonTCerezoMRobertGLucianoFPuissantAMetformin inhibits melanoma development through autophagy and apoptosis mechanismsCell Death Dis20112e10.1038/cddisOpen DOISearch in Google Scholar
Taghian A, Suit H, Pardo F, Gioioso D, Tomkinson K, DuBois W, et al. In vitro intrinsic radiation sensitivity of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 1992; 23: 55-62.10.1016/0360-3016(92)90543-Q1315313TaghianASuitHPardoFGioiosoDTomkinsonKDuBoisWIn vitro intrinsic radiation sensitivity of glioblastoma multiformeInt J Radiat Oncol Biol Phys1992235562Open DOISearch in Google Scholar
Harrabi S, Combs SE, Brons S, Haberer T, Debus J, Weber KJ. Temozolomide in combination with carbon ion or photon irradiation in glioblastoma multiforme cell lines - does scheduling matter? Int J Radiat Biol 2013; 89: 692-7. 10.3109/0955300223577964HarrabiSCombsSEBronsSHabererTDebusJWeberKJ.Temozolomide in combination with carbon ion or photon irradiation in glioblastoma multiforme cell lines - does scheduling matter?Int J Radiat Biol201389692710.3109/09553002Open DOISearch in Google Scholar
Yu Z, Zhao G, Li P, Li Y, Zhou G, Chen Y, et al. Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells. Oncol Lett 2016; 11: 2792-800. 10.3892/ol.2016.431527073554YuZZhaoGLiPLiYZhouGChenYTemozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cellsOncol Lett201611279280010.3892/ol.2016.4315Open DOISearch in Google Scholar
Shi WY, Xiao D, Wang L, Dong LH, Yan ZX, Shen ZX, et al. Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis 2012; 3: e275. 10.1038/cddisShiWYXiaoDWangLDongLHYanZXShenZXTherapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagyCell Death Dis20123e10.1038/cddisOpen DOISearch in Google Scholar
Zheng B, Jeong JH, Asara JM, Yuan YY, Granter SR, Chin L, et al. Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol Cell 2009; 33: 237-47. 10.1016/j.molcel.2008.12.02619187764ZhengBJeongJHAsaraJMYuanYYGranterSRChinLOncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferationMol Cell2009332374710.1016/j.molcel.2008.12.026Open DOISearch in Google Scholar
Rios M, Foretz M, Viollet B, Prieto A, Fraga M, Costoya JA, et al. AMPK activation by oncogenesis is required to maintain cancer cell proliferation in astrocytic tumors. Cancer Res 2013; 73: 2628-38. 10.1158/0008-547223370326RiosMForetzMViolletBPrietoAFragaMCostoyaJAAMPK activation by oncogenesis is required to maintain cancer cell proliferation in astrocytic tumorsCancer Res20137326283810.1158/0008-5472Open DOISearch in Google Scholar
Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP, et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2003; 2: 28. 10.1186/1475-4924-2-2814511394HawleySABoudeauJReidJLMustardKJUddLMakelaTPComplexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascadeJ Biol200322810.1186/1475-4924-2-28Open DOISearch in Google Scholar
Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U SA 2004; 101: 3329-35.10.1073/pnas.030806110014985505ShawRJKosmatkaMBardeesyNHurleyRLWittersLADePinhoRAThe tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stressProc Natl Acad Sci U S A200410133293510.1073/pnas.0308061100Open DOISearch in Google Scholar
Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003; 13: 2004-8.1461482810.1016/j.cub.2003.10.031WoodsAJohnstoneSRDickersonKLeiperFCFryerLGNeumannDLKB1 is the upstream kinase in the AMP-activated protein kinase cascadeCurr Biol20031320048Search in Google Scholar
Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005; 18: 283-93. 10.1016/j.molcel15866171JonesRGPlasDRKubekSBuzzaiMMuJXuYAMP-activated protein kinase induces a p53-dependent metabolic checkpointMol Cell2005182839310.1016/j.molcelOpen DOISearch in Google Scholar
Fogarty S, Hardie DG. Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta 2010; 1804: 581-91. 10.1016/j.bbapap19778642FogartySHardieDG.Development of protein kinase activators: AMPK as a target in metabolic disorders and cancerBiochim Biophys Acta201018045819110.1016/j.bbapapOpen DOISearch in Google Scholar
Guo D, Cloughesy TF, Radu CG, Mischel PS. AMPK: A metabolic checkpoint that regulates the growth of EGFR activated glioblastomas. Cell Cycle 2010; 9: 211-2. 10.4161/cc20023392GuoDCloughesyTFRaduCGMischelPS.AMPK: A metabolic checkpoint that regulates the growth of EGFR activated glioblastomasCell Cycle20109211210.4161/ccOpen DOISearch in Google Scholar
Isakovic A, Harhaji L, Stevanovic D, Markovic Z, Sumarac-Dumanovic M, Starcevic V, et al. Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis. Cell Mol Life Sci 2007; 64: 1290-302. 10.1007/s00018-007-7080-417447005IsakovicAHarhajiLStevanovicDMarkovicZSumarac-DumanovicMStarcevicVDual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosisCell Mol Life Sci200764129030210.1007/s00018-007-7080-4Open DOISearch in Google Scholar
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. 10.1158/0008-5472.CAN-09-041819679549KisfalviKEiblGSinnett-SmithJRozengurtE.Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growthCancer Res20096965394510.1158/0008-5472.CAN-09-0418Open DOISearch in Google Scholar
Sato A, Sunayama J, Okada M, Watanabe E, Seino S, Shibuya K, et al. Gliomainitiating cell elimination by metformin activation of FOXO3 via AMPK. Stem Cell Trans Med 2012; 1: 811-24. 10.5966/sctm.2012-0058SatoASunayamaJOkadaMWatanabeESeinoSShibuyaKGliomainitiating cell elimination by metformin activation of FOXO3 via AMPKStem Cell Trans Med201218112410.5966/sctm.2012-0058Open DOISearch in Google Scholar
