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2000
Volume 33, Issue 2
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Prostaglandin E2 (PGE2) plays a crucial role in inflammation. Non-steroidal anti-inflammatory medications are commonly utilized to alleviate pain and address inflammation by blocking the production of PGE2 and cyclooxygenase (COX). However, selective inhibition of COX can easily lead to a series of risks for cardiovascular diseases. Hence, it is imperative to discover safer and more efficient targets for reducing inflammation. Research has demonstrated that mPGES-1 serves as the final enzyme that controls the rate of prostaglandin E2 synthesis. Moreover, it is only triggered by inflammation and could serve as a possible treatment target instead of COX in cases of inflammation. 2,5-dimethylcelecoxib (DMC) can effectively inhibit mPGES-1 expression, maintain the overall balance of prostaglandins, reduce the secretion of PGE2, and, most importantly, avoid the side effects of COX inhibitors. DMC has the ability to address illnesses through the stimulation of autophagy and apoptosis, as well as the regulation of the immune microenvironment and intestinal flora. This study provides a comprehensive overview of the advancements in DMC within experimental research and offers suggestions for potential avenues of future investigation.

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References

  1. SzetoC.C. SuganoK. WangJ.G. FujimotoK. WhittleS. ModiG.K. ChenC.H. ParkJ.B. TamL.S. VareesangthipK. TsoiK.K.F. ChanF.K.L. Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: Joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations.Gut202069461762910.1136/gutjnl‑2019‑31930031937550
     [Google Scholar]
  2. OuraK. MorishitaA. TaniJ. MasakiT. Tumor immune microenvironment and immunosuppressive therapy in hepatocellular carcinoma: A review.Int. J. Mol. Sci.20212211580110.3390/ijms2211580134071550
     [Google Scholar]
  3. RizzoA. MollicaV. MassariF. Expression of programmed cell death ligand 1 as a predictive biomarker in metastatic urothelial carcinoma patients treated with first- line immune checkpoint inhibitors versus chemotherapy: A systematic review and meta-analysis.Eur. Urol. Focus20228115215910.1016/j.euf.2021.01.00333516645
     [Google Scholar]
  4. Di FedericoA. MoscaM. PaganiR. CarloniR. FregaG. De GiglioA. RizzoA. RicciD. TavolariS. Di MarcoM. PalloniA. BrandiG. Immunotherapy in pancreatic cancer: Why do we keep failing? A focus on tumor immune microenvironment, predictive biomarkers and treatment outcomes.Cancers (Basel)20221410242910.3390/cancers1410242935626033
     [Google Scholar]
  5. Ramos-CasalsM. BrahmerJ.R. CallahanM.K. Flores-ChávezA. KeeganN. KhamashtaM.A. LambotteO. MarietteX. PratA. Suárez-AlmazorM.E. Immune-related adverse events of checkpoint inhibitors.Nat. Rev. Dis. Primers2020613810.1038/s41572‑020‑0160‑632382051
     [Google Scholar]
  6. GuvenD.C. ErulE. KaygusuzY. AkagunduzB. KilickapS. De LucaR. RizzoA. Immune checkpoint inhibitor-related hearing loss: A systematic review and analysis of individual patient data.Supportive Care in Cancer20233112624
     [Google Scholar]
  7. RizzoA. SantoniM. MollicaV. LogulloF. RoselliniM. MarchettiA. FaloppiL. BattelliN. MassariF. Peripheral neuropathy and headache in cancer patients treated with immunotherapy and immuno-oncology combinations: The MOUSEION-02 study.Expert Opin. Drug Metab. Toxicol.202117121455146610.1080/17425255.2021.202940535029519
     [Google Scholar]
  8. DeckmannK. RörschF. SteriR. Schubert-ZsilaveczM. GeisslingerG. GröschS. Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-κB.Biochem. Pharmacol.20108091365137210.1016/j.bcp.2010.07.03220688046
     [Google Scholar]
  9. PyrkoP. SorianoN. KardoshA. LiuY.T. UddinJ. PetasisN.A. HofmanF.M. ChenC.S. ChenT.C. SchönthalA.H. Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC), in tumor cells in vitro and in vivo.Mol. Cancer2006511910.1186/1476‑4598‑5‑1916707021
     [Google Scholar]
  10. TanT. FuX. QuJ. ZhangM. ChenH. WangY. WangB. LiJ. LiuJ. LiuP. 2,5-dimethyl celecoxib induces apoptosis and autophagy via activation of ROS/JNK axis in nasopharyngeal carcinoma cells.Aging (Albany NY)20211317214832149610.18632/aging.20348834511433
     [Google Scholar]
  11. ChenZ. ChenY. PengL. WangX. TangN. 2,5-dimethylcelecoxib improves immune microenvironment of hepatocellular carcinoma by promoting ubiquitination of HBx-induced PD-L1.J. Immunother. Cancer202082e00137710.1136/jitc‑2020‑00137733028694
     [Google Scholar]
  12. ChenS. LiuX. YueP. SchönthalA.H. KhuriF.R. SunS.Y. CCAAT/enhancer binding protein homologous protein-dependent death receptor 5 induction and ubiquitin/proteasome-mediated cellular FLICE-inhibitory protein down-regulation contribute to enhancement of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by dimethyl-celecoxib in human non small-cell lung cancer cells.Mol. Pharmacol.20077251269127910.1124/mol.107.03746517684158
     [Google Scholar]
  13. GretenF.R. EckmannL. GretenT.F. ParkJ.M. LiZ.W. EganL.J. KagnoffM.F. KarinM. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer.Cell2004118328529610.1016/j.cell.2004.07.01315294155
     [Google Scholar]
  14. GrivennikovS. KarinE. TerzicJ. MucidaD. YuG.Y. VallabhapurapuS. SchellerJ. Rose-JohnS. CheroutreH. EckmannL. KarinM. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer.Cancer Cell200915210311310.1016/j.ccr.2009.01.00119185845
     [Google Scholar]
  15. GrivennikovS.I. GretenF.R. KarinM. Immunity, inflammation, and cancer.Cell2010140688389910.1016/j.cell.2010.01.02520303878
     [Google Scholar]
  16. WangD. CabalagC.S. ClemonsN.J. DuBoisR.N. Cyclooxygenases and prostaglandins in tumor immunology and microenvironment of gastrointestinal cancer.Gastroenterology202116161813182910.1053/j.gastro.2021.09.05934606846
     [Google Scholar]
  17. XiaD. WangD. KimS.H. KatohH. DuBoisR.N. Prostaglandin E2 promotes intestinal tumor growth via DNA methylation.Nat. Med.201218222422610.1038/nm.260822270723
     [Google Scholar]
  18. WongC.C. KangW. XuJ. QianY. LukS.T.Y. ChenH. LiW. ZhaoL. ZhangX. ChiuP.W.Y. NgE.K.W. YuJ. Prostaglandin E2 induces DNA hypermethylation in gastric cancer in vitro and in vivo.Theranostics20199216256626810.7150/thno.3576631534549
     [Google Scholar]
  19. PawitanY. YinL. SetiawanA. AuerG. SmedbyK.E. CzeneK. Distinct effects of anti-inflammatory and anti-thrombotic drugs on cancer characteristics at diagnosis.Eur. J. Cancer20155167517
     [Google Scholar]
  20. DasS. ChandrasekharS. YadavJ.S. GréeR. Recent developments in the synthesis of prostaglandins and analogues.Chem. Rev.200710773286333710.1021/cr068365a17590055
     [Google Scholar]
  21. TaniokaT. NakataniY. SemmyoN. MurakamiM. KudoI. Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis.J. Biol. Chem.200027542327753278210.1074/jbc.M00350420010922363
     [Google Scholar]
  22. GrahamD.J. CampenD. HuiR. SpenceM. CheethamC. LevyG. ShoorS. RayW.A. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: Nested case- control study.Lancet2005365945847548110.1016/S0140‑6736(05)17864‑715705456
     [Google Scholar]
  23. BresalierR.S. SandlerR.S. QuanH. BologneseJ.A. OxeniusB. HorganK. LinesC. RiddellR. MortonD. LanasA. KonstamM.A. BaronJ.A. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.N. Engl. J. Med.2005352111092110210.1056/NEJMoa05049315713943
     [Google Scholar]
  24. ChengY. WangM. YuY. LawsonJ. FunkC.D. FitzgeraldG.A. Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function.J. Clin. Invest.200611651391139910.1172/JCI2754016614756
     [Google Scholar]
  25. ChenL. YangG. MonslowJ. ToddL. CormodeD.P. TangJ. GrantG.R. DeLongJ.H. TangS.Y. LawsonJ.A. PureE. FitzGeraldG.A. Myeloid cell microsomal prostaglandin E synthase-1 fosters atherogenesis in mice.Proc. Natl. Acad. Sci. USA2014111186828683310.1073/pnas.140179711124753592
     [Google Scholar]
  26. CiminoP. KeeneC. BreyerR. MontineK. MontineT. Therapeutic targets in prostaglandin E2 signaling for neurologic disease.Curr. Med. Chem.200815191863186910.2174/09298670878513291518691044
     [Google Scholar]
  27. YangS. HuhE. MoonG.H. AhnJ. WooJ. HanH.S. LeeH.H. ChungK.S. LeeK.T. OhM.S. LeeJ.Y. In vitro and in vivo neuroprotective effect of novel mPGES-1 inhibitor in animal model of Parkinson’s disease.Bioorg. Med. Chem. Lett.20227412892010.1016/j.bmcl.2022.12892035931244
     [Google Scholar]
  28. LiL. YasmenN. HouR. YangS. LeeJ.Y. HaoJ. YuY. JiangJ. Inducible prostaglandin E synthase as a pharmacological target for ischemic stroke.Neurotherapeutics202219136638510.1007/s13311‑022‑01191‑135099767
     [Google Scholar]
  29. ClaveauD. SirinyanM. GuayJ. GordonR. ChanC.C. BureauY. RiendeauD. ManciniJ.A. Microsomal prostaglandin E synthase-1 is a major terminal synthase that is selectively up-regulated during cyclooxygenase-2-dependent prostaglandin E2 production in the rat adjuvant-induced arthritis model.J. Immunol.20031709473844
     [Google Scholar]
  30. RiendeauD. AspiotisR. EthierD. GareauY. GrimmE.L. GuayJ. GuiralS. JuteauH. ManciniJ.A. MéthotN. RubinJ. FriesenR.W. Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886.Bioorg. Med. Chem. Lett.200515143352335510.1016/j.bmcl.2005.05.02715953724
     [Google Scholar]
  31. KoeberleA. WerzO. Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders.Biochem. Pharmacol.201598111510.1016/j.bcp.2015.06.02226123522
     [Google Scholar]
  32. CôtéB. BouletL. BrideauC. ClaveauD. EthierD. FrenetteR. GagnonM. GirouxA. GuayJ. GuiralS. ManciniJ. MartinsE. MasséF. MéthotN. RiendeauD. RubinJ. XuD. YuH. DucharmeY. FriesenR.W. Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors.Bioorg. Med. Chem. Lett.200717246816682010.1016/j.bmcl.2007.10.03318029174
     [Google Scholar]
  33. ChiassonJ.F. BouletL. BrideauC. ChauA. ClaveauD. CôtéB. EthierD. GirouxA. GuayJ. GuiralS. ManciniJ. MasséF. MéthotN. RiendeauD. RoyP. RubinJ. XuD. YuH. DucharmeY. FriesenR.W. Trisubstituted ureas as potent and selective mPGES-1 inhibitors.Bioorg. Med. Chem. Lett.20112151488149210.1016/j.bmcl.2011.01.00621295979
     [Google Scholar]
  34. Singh BahiaM. Kumar KatareY. SilakariO. VyasB. SilakariP. Inhibitors of microsomal prostaglandin E2 synthase-1 enzyme as emerging anti-inflammatory candidates.Med. Res. Rev.201434482585510.1002/med.2130625019142
     [Google Scholar]
  35. ArhancetG.B. WalkerD.P. MetzS. FobianY.M. HeasleyS.E. CarterJ.S. SpringerJ.R. JonesD.E. HayesM.J. ShafferA.F. JeromeG.M. BarattaM.T. ZweifelB. MooreW.M. MasferrerJ.L. VazquezM.L. Discovery and SAR of PF-4693627, a potent, selective and orally bioavailable mPGES-1 inhibitor for the potential treatment of inflammation.Bioorg. Med. Chem. Lett.20132341114111910.1016/j.bmcl.2012.11.10923260349
     [Google Scholar]
  36. BanerjeeA. PawarM.Y. PatilS. YadavP.S. KadamP.A. KattigeV.G. DeshpandeD.S. PednekarP.V. PisatM.K. GharatL.A. Development of 2-aryl substituted quinazolin-4(3H)-one, pyrido[4,3-d]pyrimidin-4(3H)- one and pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as microsomal prostaglandin E2 synthase-1 inhibitors.Bioorg. Med. Chem. Lett.201424204838484410.1016/j.bmcl.2014.08.05625260492
     [Google Scholar]
  37. SchifflerM.A. AntonysamyS. BhattacharS.N. CampanaleK.M. ChandrasekharS. CondonB. DesaiP.V. FisherM.J. GroshongC. HarveyA. HickeyM.J. HughesN.E. JonesS.A. KimE.J. KuklishS.L. LuzJ.G. NormanB.H. RathmellR.E. RizzoJ.R. SengT.W. ThibodeauxS.J. WoodsT.A. YorkJ.S. YuX.P. Discovery and characterization of 2-acylaminoimidazole microsomal prostaglandin E synthase-1 inhibitors.J. Med. Chem.201659119420510.1021/acs.jmedchem.5b0124926653180
     [Google Scholar]
  38. KoeberleA. PollastroF. NorthoffH. WerzO. Myrtucommulone, a natural acylphloroglucinol, inhibits microsomal prostaglandin E2 synthase-1.Br. J. Pharmacol.2009156695296110.1111/j.1476‑5381.2009.00070.x19298395
     [Google Scholar]
  39. KoeberleA. BauerJ. VerhoffM. HoffmannM. NorthoffH. WerzO. Green tea epigallocatechin-3-gallate inhibits microsomal prostaglandin E2 synthase-1.Biochem. Biophys. Res. Commun.2009388235035410.1016/j.bbrc.2009.08.00519665000
     [Google Scholar]
  40. MoonY. GlasgowW.C. ElingT.E. Curcumin suppresses interleukin 1 beta-mediated microsomal prostaglandin E synthase 1 by altering early growth response gene 1 and other signaling pathways.J. Pharmacol. Exp. Ther.2005315278879510.1124/jpet.105.08443416081677
     [Google Scholar]
  41. ZhangX.D. WangY. YeL.H. Hepatitis B virus X protein accelerates the development of hepatoma.Cancer Biol. Med.201411318219025364579
     [Google Scholar]
  42. LiuC. ChenS. WangX. ChenY. TangN. 15d-PGJ2 decreases PGE 2 synthesis in HBx-positive liver cells by interfering EGR1 binding to mPGES-1 promoter.Biochem. Pharmacol.201491333734710.1016/j.bcp.2014.07.03225108236
     [Google Scholar]
  43. XuD. CaiJ. WanZ. GaoH. SunY. Pathophysiological role of prostaglandin E synthases in liver diseases.Prostaglandins Other Lipid Mediat.202115410655210.1016/j.prostaglandins.2021.10655233930567
     [Google Scholar]
  44. MaY. WangX. TangN. Downregulation of mPGES-1 expression via EGR1 Plays an important role in inhibition of caffeine on PGE2 synthesis of HBx(+) hepatocytes.Mediators Inflamm.20152015137275010.1155/2015/37275026538827
     [Google Scholar]
  45. HenkelJ. ColemanC.D. SchraplauA. JöhrensK. WeissT.S. JonasW. SchürmannA. PüschelG.P. Augmented liver inflammation in a microsomal prostaglandin E synthase 1 (mPGES-1)-deficient diet-induced mouse NASH model.Sci. Rep.2018811612710.1038/s41598‑018‑34633‑y30382148
     [Google Scholar]
  46. CeddiaR.P. LeeD. MaulisM.F. CarboneauB.A. ThreadgillD.W. PoffenbergerG. MilneG. BoydK.L. PowersA.C. McGuinnessO.P. GannonM. BreyerR.M. The PGE2 EP3 receptor regulates diet-induced adiposity in male mice.Endocrinology2016157122023210.1210/en.2015‑169326485614
     [Google Scholar]
  47. ZhangT. MaY. XuK.Q. HuangW.Q. Pretreatment of parecoxib attenuates hepatic ischemia/reperfusion injury in rats.BMC Anesthesiol.201515116510.1186/s12871‑015‑0147‑026577339
     [Google Scholar]
  48. LlovetJ.M. BurroughsA. BruixJ. Hepatocellular carcinoma.Lancet200336293991907191710.1016/S0140‑6736(03)14964‑114667750
     [Google Scholar]
  49. El-SeragH.B. Hepatocellular carcinoma: Recent trends in the United States.Gastroenterology20041275Suppl. 1S27S3410.1053/j.gastro.2004.09.01315508094
     [Google Scholar]
  50. KernM.A. BreuhahnK. SchirmacherP. Molecular pathogenesis of human hepatocellular carcinoma.Adv. Cancer Res.2002866711210.1016/S0065‑230X(02)86003‑112374281
     [Google Scholar]
  51. ChangH.H. MeuilletE.J. Identification and development of mPGES-1 inhibitors: Where we are at?Future Med. Chem.20113151909193410.4155/fmc.11.13622023034
     [Google Scholar]
  52. YoshimatsuK. AltorkiN.K. GolijaninD. ZhangF. JakobssonP.J. DannenbergA.J. SubbaramaiahK. Inducible prostaglandin E synthase is overexpressed in non- small cell lung cancer.Clin. Cancer Res.2001792669267411555578
     [Google Scholar]
  53. HyodoT. ItoY. HosonoK. UematsuS. AkiraS. MajimaM. TakedaA. AmanoH. The role of mPGES-1 in promoting granulation tissue angiogenesis through regulatory T-cell accumulation.In Vivo20223652061207310.21873/invivo.1293236099134
     [Google Scholar]
  54. AmanoH. HaysahiI. YoshidaS. YoshimuraH. MajimaM. Cyclooxygenase-2 and adenylate cyclase/protein kinase A signaling pathway enhances angiogenesis through induction of vascular endothelial growth factor in rat sponge implants.Hum. Cell2002151132410.1111/j.1749‑0774.2002.tb00095.x12126060
     [Google Scholar]
  55. MajimaM. HayashiI. MuramatsuM. KatadaJ. YamashinaS. KatoriM. Cyclo-oxygenase-2 enhances basic fibroblast growth factor-induced angiogenesis through induction of vascular endothelial growth factor in rat sponge implants.Br. J. Pharmacol.2000130364164910.1038/sj.bjp.070332710821793
     [Google Scholar]
  56. Steinmetz-SpähJ. JakobssonP.J. The anti-inflammatory and vasoprotective properties of mPGES-1 inhibition offer promising therapeutic potential.Expert Opin. Ther. Targets202327111115112310.1080/14728222.2023.228578538015194
     [Google Scholar]
  57. WangM. LeeE. SongW. RicciottiE. RaderD.J. LawsonJ.A. PuréE. FitzGeraldG.A. Microsomal prostaglandin E synthase-1 deletion suppresses oxidative stress and angiotensin II-induced abdominal aortic aneurysm formation.Circulation2008117101302130910.1161/CIRCULATIONAHA.107.73139818285567
     [Google Scholar]
  58. WernerN. NickenigG. SinningJ.M. Complex PCI procedures: challenges for the interventional cardiologist.Clin. Res. Cardiol.2018107S2Suppl. 2647310.1007/s00392‑018‑1316‑129978353
     [Google Scholar]
  59. ZhuL. XuC. HuoX. HaoH. WanQ. ChenH. ZhangX. BreyerR.M. HuangY. CaoX. LiuD.P. FitzGeraldG.A. WangM. The cyclooxygenase-1/mPGES-1/endothelial prostaglandin EP4 receptor pathway constrains myocardial ischemia-reperfusion injury.Nat. Commun.2019101188810.1038/s41467‑019‑09492‑431015404
     [Google Scholar]
  60. FainJ.N. KanuA. BahouthS.W. CowanG.S.M.Jr HilerM.L. LefflerC.W. Comparison of PGE2, prostacyclin and leptin release by human adipocytes versus explants of adipose tissue in primary culture.Prostaglandins Leukot. Essent. Fatty Acids200267646747310.1054/plef.2002.043012468269
     [Google Scholar]
  61. García-AlonsoV. ClàriaJ. Prostaglandin E2 signals white-to-brown adipogenic differentiation.Adipocyte20143429029610.4161/adip.2999326317053
     [Google Scholar]
  62. Ballesteros-MartínezC. Rodrigues-DíezR. BeltránL.M. Moreno-CarrilesR. Martínez-MartínezE. González-AmorM. Martínez-GonzálezJ. RodríguezC. CachofeiroV. SalaicesM. BrionesA.M. Microsomal prostaglandin E synthase-1 is involved in the metabolic and cardiovascular alterations associated with obesity.Br. J. Pharmacol.2022179112733275310.1111/bph.1577634877656
     [Google Scholar]
  63. MasedaD. BanerjeeA. JohnsonE.M. WashingtonM.K. KimH. LauK.S. CroffordL.J. mPGES-1-mediated production of PGE2 and EP4 receptor sensing regulate T cell colonic inflammation.Front. Immunol.20189295410.3389/fimmu.2018.0295430619314
     [Google Scholar]
  64. MuthuswamyR. Mueller-BerghausJ. HaberkornU. ReinhartT.A. SchadendorfD. KalinskiP. PGE2 transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells.Blood201011691454145910.1182/blood‑2009‑12‑25803820498301
     [Google Scholar]
  65. MonradS.U. KojimaF. KapoorM. KuanE.L. SarkarS. RandolphG.J. CroffordL.J. Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells and alters the cytokine profile, but does not affect maturation or migration.Prostaglandins Leukot. Essent. Fatty Acids2011843-411312110.1016/j.plefa.2010.10.00321190819
     [Google Scholar]
  66. DuffinR. O’ConnorR.A. CrittendenS. ForsterT. YuC. ZhengX. SmythD. RobbC.T. RossiF. SkourasC. TangS. RichardsJ. PellicoroA. WellerR.B. BreyerR.M. MoleD.J. IredaleJ.P. AndertonS.M. NarumiyaS. MaizelsR.M. GhazalP. HowieS.E. RossiA.G. YaoC. Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis.Science201635162791333133810.1126/science.aad990326989254
     [Google Scholar]
  67. NakanishiM. RosenbergD.W. Multifaceted roles of PGE2 in inflammation and cancer.Semin. Immunopathol.201335212313710.1007/s00281‑012‑0342‑822996682
     [Google Scholar]
  68. SchumacherY. AparicioT. OurabahS. BarailleF. MartinA. WindP. DentinR. PosticC. GuilmeauS. Dysregulated CRTC1 activity is a novel component of PGE2 signaling that contributes to colon cancer growth.Oncogene201635202602261410.1038/onc.2015.28326300003
     [Google Scholar]
  69. SasakiY. NakataniY. HaraS. Role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 in colon carcinogenesis.Prostaglandins Other Lipid Mediat.2015121Pt A425
     [Google Scholar]
  70. KalinskiP. Regulation of immune responses by prostaglandin E2.J. Immunol.20121881218
     [Google Scholar]
  71. RoulisM. NikolaouC. KotsakiE. KaffeE. KaragianniN. KoliarakiV. SalpeaK. RagoussisJ. AidinisV. MartiniE. BeckerC. HerschmanH.R. VetranoS. DaneseS. KolliasG. Intestinal myofibroblast-specific Tpl2- Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis.Proc. Natl. Acad. Sci. USA201411143E4658E466710.1073/pnas.141576211125316791
     [Google Scholar]
  72. HaoC.M. BreyerM.D. Physiological regulation of prostaglandins in the kidney.Annu. Rev. Physiol.200870135737710.1146/annurev.physiol.70.113006.10061417988207
     [Google Scholar]
  73. SamuelssonB. MorgensternR. JakobssonP.J. Membrane prostaglandin E synthase-1: A novel therapeutic target.Pharmacol. Rev.200759320722410.1124/pr.59.3.117878511
     [Google Scholar]
  74. JiaZ. WangH. YangT. Microsomal prostaglandin E synthase 1 deletion retards renal disease progression but exacerbates anemia in mice with renal mass reduction.Hypertension20125911228
     [Google Scholar]
  75. RegnerK.R. Dual role of microsomal prostaglandin E synthase 1 in chronic kidney disease.Hypertension20125911213
     [Google Scholar]
  76. SluterM.N. LiQ. YasmenN. ChenY. LiL. HouR. YuY. YangC.Y. MeibohmB. JiangJ. The inducible prostaglandin E synthase (mPGES-1) in neuroinflammatory disorders.Exp. Biol. Med. (Maywood)2023248981181910.1177/1535370223117992637515545
     [Google Scholar]
  77. SangN. ZhangJ. MarcheselliV. BazanN.G. ChenC. Postsynaptically synthesized prostaglandin E2 (PGE2) modulates hippocampal synaptic transmission via a presynaptic PGE2 EP2 receptor.J. Neurosci.200525439858987010.1523/JNEUROSCI.2392‑05.200516251433
     [Google Scholar]
  78. NakanoY. KurodaE. KitoT. UematsuS. AkiraS. YokotaA. NishizawaS. YamashitaU. Induction of prostaglandin E2 synthesis and microsomal prostaglandin E synthase-1 expression in murine microglia by glioma-derived soluble factors.J. Neurosurg.2008108231131910.3171/JNS/2008/108/2/031118240928
     [Google Scholar]
  79. ZhuJ. SongX. LinH.P. YoungD.C. YanS. MarquezV.E. ChenC.S. Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents.J. Natl. Cancer Inst.200294231745175710.1093/jnci/94.23.174512464646
     [Google Scholar]
  80. WangC. ChenY. WangY. LiuX. LiuY. LiY. ChenH. FanC. WuD. YangJ. Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1.J. Exp. Clin. Cancer Res.201938137110.1186/s13046‑019‑1361‑231438982
     [Google Scholar]
  81. PritchardR. Rodríguez-EnríquezS. Pacheco-VelázquezS.C. BortnikV. Moreno-SánchezR. RalphS. Celecoxib inhibits mitochondrial O2 consumption, promoting ROS dependent death of murine and human metastatic cancer cells via the apoptotic signalling pathway.Biochem. Pharmacol.201815431833410.1016/j.bcp.2018.05.01329800556
     [Google Scholar]
  82. CocaR. SolerF. Cortés-CastellE. Gil-GuillénV. Fernández-BeldaF. Inhibition mechanism of the intracellular transporter Ca2+-pump from sarco-endoplasmic reticulum by the antitumor agent dimethyl-celecoxib.PLoS One201497e10208310.1371/journal.pone.010208325003576
     [Google Scholar]
  83. LeeS.H. MoonH.J. LeeY.S. KangC.D. KimS.H. Potentiation of TRAIL-induced cell death by nonsteroidal anti-inflammatory drug in human hepatocellular carcinoma cells through the ER stress-dependent autophagy pathway.Oncol. Rep.20204431136114810.3892/or.2020.766232705218
     [Google Scholar]
  84. KardoshA. GoldenE.B. PyrkoP. UddinJ. HofmanF.M. ChenT.C. LouieS.G. PetasisN.A. SchönthalA.H. Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib.Cancer Res.200868384385110.1158/0008‑5472.CAN‑07‑555518245486
     [Google Scholar]
  85. PyrkoP. KardoshA. LiuY.T. SorianoN. XiongW. ChowR.H. UddinJ. PetasisN.A. MircheffA.K. FarleyR.A. LouieS.G. ChenT.C. SchönthalA.H. Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a non-coxib analogue of celecoxib.Mol. Cancer Ther.2007641262127510.1158/1535‑7163.MCT‑06‑062917431104
     [Google Scholar]
  86. SobolewskiC. RhimJ. LegrandN. MullerF. CerellaC. MackF. ChateauvieuxS. KimJ.G. YoonA.Y. KimK.W. DicatoM. DiederichM. 2,5-dimethyl-celecoxib inhibits cell cycle progression and induces apoptosis in human leukemia cells.J. Pharmacol. Exp. Ther.2015355230832810.1124/jpet.115.22501126330537
     [Google Scholar]
  87. KardoshA. WangW. UddinJ. PetasisN.A. HofmanF.M. ChenT.C. SchönthalA.H. Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2-inhibitory function, potently mimics the anti-tumor effects of celecoxib on burkitt’s lymphoma in vitro and in vivo.Cancer Biol. Ther.20054557158210.4161/cbt.4.5.169915846081
     [Google Scholar]
  88. ChouJ.P. RamirezC.M. RybaD.M. KoduriM.P. EffrosR.B. Prostaglandin E2 promotes features of replicative senescence in chronically activated human CD8+ T cells.PLoS One201496e9943210.1371/journal.pone.009943224918932
     [Google Scholar]
  89. YeB. LiuX. LiX. KongH. TianL. ChenY. T-cell exhaustion in chronic hepatitis B infection: Current knowledge and clinical significance.Cell Death Dis.201563e169410.1038/cddis.2015.4225789969
     [Google Scholar]
  90. PiC. JingP. LiB. FengY. XuL. XieK. HuangT. XuX. GuH. FangJ. Reversing PD-1 resistance in B16F10 cells and recovering tumour immunity using a COX2 inhibitor.Cancers (Basel)20221417413410.3390/cancers1417413436077671
     [Google Scholar]
  91. PanB. ChenZ. ZhangX. WangZ. YaoY. WuX. QiuJ. LinH. YuL. TuH. TangN. 2,5-dimethylcelecoxib alleviated NK and T-cell exhaustion in hepatocellular carcinoma via the gastrointestinal microbiota-AMPK-mTOR axis.J. Immunother. Cancer2023116e00681710.1136/jitc‑2023‑00681737316264
     [Google Scholar]
  92. RogersM.A.M. AronoffD.M. The influence of non- steroidal anti-inflammatory drugs on the gut microbiome.Clin. Microbiol. Infect.2016222178
     [Google Scholar]
  93. FujitaA. Takahashi-YanagaF. MorimotoS. YoshiharaT. AriokaM. IgawaK. TomookaK. HokaS. SasaguriT. 2,5-dimethylcelecoxib prevents pressure-induced left ventricular remodeling through GSK-3 activation.Hypertens. Res.2017402130139
     [Google Scholar]
  94. MorishigeS. Takahashi-YanagaF. IshikaneS. AriokaM. IgawaK. KurooA. TomookaK. ShioseA. SasaguriT. 2,5-dimethylcelecoxib prevents isoprenaline-induced cardiomyocyte hypertrophy and cardiac fibroblast activation by inhibiting Akt-mediated GSK-3 phosphorylation.Biochem. Pharmacol.2019168829010.1016/j.bcp.2019.06.01831229551
     [Google Scholar]
  95. YamamotoM. Takahashi-YanagaF. AriokaM. IgawaK. TomookaK. YamauraK. SasaguriT. Cardiac and renal protective effects of 2,5-dimethylcelecoxib in angiotensin II and high-salt-induced hypertension model mice.J. Hypertens.202139589290310.1097/HJH.000000000000272833252422
     [Google Scholar]
  96. EgashiraI. Takahashi-YanagaF. NishidaR. AriokaM. IgawaK. TomookaK. NakatsuY. TsuzukiT. NakabeppuY. KitazonoT. SasaguriT. Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/β-catenin signaling pathway.Cancer Sci.2017108110811510.1111/cas.1310627761963
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673327820241004042817
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Experimental Research Progress of mPGES-1 Inhibitor 2,5-dimethylcelecoxib in Various Diseases
Curr. Med. Chem. 33, 299 (2026); https://doi.org/10.2174/0109298673327820241004042817
/content/journals/cmc/10.2174/0109298673327820241004042817
/content/journals/cmc/10.2174/0109298673327820241004042817
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  • Article Type:     Review Article
Keyword(s): arachidonic acid (AA); clooxygenase (COX); dimethylcelecoxib; Inflammation; mPGES-1 inhibitor; prostaglandin E2

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