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2000
Volume 32, Issue 6
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Introduction

This study aimed to investigate the anti-carcinogenic effects of recombinant L- methioninase (rBlmet) on the pancreatic cancer cell line MiaPaCa-2.

Methods

In this study, rBlmet was initially cloned, expressed, and purified. To increase enzyme activity, the His-tags on the enzyme were removed using thrombin. rBlmet was then applied to MiaPaCa-2 cells, and the cell viability of MiaPaCa-2 cells was evaluated by neutral red assay after rBlmet treatment. The combined effect of etoposide with rBlmet against MiaPaCa-2 cells was also evaluated for 12 and 24 hours using a neutral red assay. Furthermore, cell morphology was evaluated by Giemsa and DAPI/F-actin staining methods. Survivin and caspase-3 gene expression levels were measured by RT-qPCR.

Results and Discussion

The specific activity of the enzyme increased after His-tag elimination to 5.62 µmol/mg per minute. rBlmet showed a significant cytotoxic effect on the MiaPaCa-2 cell line. The IC value (24 h) of rBlmet for MiaPaCa-2 cells was 3.02 U/mL. In addition, rBlmet increased the cytotoxic effect of etoposide on the MiaPaCa-2 cell line, while it showed less effect on HaCat, which is a normal human cell line. Furthermore, rBlmet increased caspase-3 expression and downregulated survivin gene expression in MiaPaCa-2 cell lines. It successfully inhibited the growth of Mia-PaCa-2 cells by exploiting exogenous methionine amino acid in the growth medium. This study revealed promising results. However, further studies are needed on additional pancreatic cancer cell lines and models.

Conclusion

Based on these findings, it can be concluded that rBlmet not only has great potential to treat pancreatic cancer in the future but can also be used as an adjuvant to enhance the effectiveness of chemotherapeutic agents like etoposide.

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References

  1. İpekS.L. GöktürkD. Evaluation of artificial neural network and adaptive-network-based fuzzy inference system for ovarian and lung cancer prediction.J. Health Sci. Med.202471808810.32322/jhsm.1360782
     [Google Scholar]
  2. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
     [Google Scholar]
  3. JaviaB.M. GadhviM.S. VyasS.J. GhelaniA. WirajanaN. DudhagaraD.R. A review on L-methioninase in cancer therapy: Precision targeting, advancements and diverse applications for a promising future.Int. J. Biol. Macromol.2024265Pt 213099710.1016/j.ijbiomac.2024.13099738508568
     [Google Scholar]
  4. SharmaB. DeviS. KumarR. KanwarS.S. Screening, characterization and anti-cancer application of purified intracellular MGL.Int. J. Biol. Macromol.20222179611010.1016/j.ijbiomac.2022.07.02635817235
     [Google Scholar]
  5. RahmaniZ. SafariF. Evaluating the in vitro therapeutic effects of human amniotic mesenchymal stromal cells on MiaPaca2 pancreatic cancer cells using 2D and 3D cell culture model.Tissue Cell20216810147910.1016/j.tice.2020.10147933383360
     [Google Scholar]
  6. JemalA. BrayF. CenterM.M. FerlayJ. WardE. FormanD. Global cancer statistics.CA Cancer J. Clin.2011612699010.3322/caac.2010721296855
     [Google Scholar]
  7. SiegelR. MaJ. ZouZ. JemalA. Cancer statistics, 2014.CA Cancer J. Clin.201464192910.3322/caac.2120824399786
     [Google Scholar]
  8. LauM.K. DavilaJ.A. ShaibY.H. Incidence and survival of pancreatic head and body and tail cancers: A population-based study in the United States.Pancreas201039445846210.1097/MPA.0b013e3181bd648919924019
     [Google Scholar]
  9. QuaresmaM. ColemanM.P. RachetB. 40-year trends in an index of survival for all cancers combined and survival adjusted for age and sex for each cancer in England and Wales, 1971–2011: A population-based study.Lancet201538599741206121810.1016/S0140‑6736(14)61396‑925479696
     [Google Scholar]
  10. HidalgoM. CascinuS. KleeffJ. LabiancaR. LöhrJ.M. NeoptolemosJ. RealF.X. Van LaethemJ.L. HeinemannV. Addressing the challenges of pancreatic cancer: Future directions for improving outcomes.Pancreatology201515181810.1016/j.pan.2014.10.00125547205
     [Google Scholar]
  11. LiX. HuangD. ZhangQ. GuoC. FuQ. ZhangX. TangT.Y. SuW. ChenY.W. ChenW. MaT. GaoS.L. QueR.S. BaiX.L. LiangT.B. The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.Pancreatology20202019510010.1016/j.pan.2019.11.01231786057
     [Google Scholar]
  12. SowersM.L. SowersL.C. Glioblastoma and methionine addiction.Int. J. Mol. Sci.20222313715610.3390/ijms2313715635806160
     [Google Scholar]
  13. Abo QouraL. BalakinK.V. HoffmanR.M. PokrovskyV.S. The potential of methioninase for cancer treatment.Biochim. Biophys. Acta Rev. Cancer20241879418912210.1016/j.bbcan.2024.189122
     [Google Scholar]
  14. SugimuraT. BirnbaumS.M. WinitzM. GreensteinJ.P. Quantitative nutritional studies with water-soluble, chemically defined diets. VIII. The forced feeding of diets each lacking in one essential amino acid.Arch. Biochem. Biophys.195981244845510.1016/0003‑9861(59)90225‑513638009
     [Google Scholar]
  15. HoffmanR.M. ErbeR.W. High in vivos rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine.Proc. Natl. Acad. Sci. USA19767351523152710.1073/pnas.73.5.1523179090
     [Google Scholar]
  16. WangZ. YipL.Y. LeeJ.H.J. WuZ. ChewH.Y. ChongP.K.W. TeoC.C. AngH.Y.K. PehK.L.E. YuanJ. MaS. ChooL.S.K. BasriN. JiangX. YuQ. HillmerA.M. LimW.T. LimT.K.H. TakanoA. TanE.H. TanD.S.W. HoY.S. LimB. TamW.L. Methionine is a metabolic dependency of tumor-initiating cells.Nat. Med.201925582583710.1038/s41591‑019‑0423‑531061538
     [Google Scholar]
  17. KaiserP. Methionine dependence of cancer.Biomolecules202010456810.3390/biom1004056832276408
     [Google Scholar]
  18. PokrovskyV.S. Abo QouraL. MorozovaE. BunikV.I. Predictive markers for efficiency of the amino-acid deprivation therapies in cancer.Front. Med.20229103535610.3389/fmed.2022.103535636405587
     [Google Scholar]
  19. SuganyaK. GovindanK. PrabhaP. MuruganM. An extensive review on L-methioninase and its potential applications.Biocatal. Agric. Biotechnol.20171210411510.1016/j.bcab.2017.09.009
     [Google Scholar]
  20. KreisW. HessionC. Isolation and purification of l-methionine-α-deamino-γ-mercaptomethane-lyase (l-methioninase) from Clostridium sporogenes.Cancer Res.1973338186218654720797
     [Google Scholar]
  21. HoffmanR.M. TanY. LiS. HanQ. YagiS. TakakuraT. Development of recombinant methioninase for cancer treatment.Methionine Dependence of Cancer and Aging. Methods in Molecular BiologyHumana PressNew York201910713110.1007/978‑1‑4939‑8796‑2_10
     [Google Scholar]
  22. SunX. YangZ. LiS. TanY. ZhangN. WangX. YagiS. YoshiokaT. TakimotoA. MitsushimaK. SuginakaA. FrenkelE.P. HoffmanR.M. In vivos efficacy of recombinant methioninase is enhanced by the combination of polyethylene glycol conjugation and pyridoxal 5′-phosphate supplementation.Cancer Res.200363238377838314678999
     [Google Scholar]
  23. YangZ. SunX. LiS. TanY. WangX. ZhangN. YagiS. TakakuraT. KobayashiY. TakimotoA. YoshiokaT. SuginakaA. FrenkelE.P. HoffmanR.M. Circulating half-life of PEGylated recombinant methioninase holoenzyme is highly dose dependent on cofactor pyridoxal-5′-phosphate.Cancer Res.200464165775577810.1158/0008‑5472.CAN‑04‑140615313919
     [Google Scholar]
  24. MachoverD. RossiL. HamelinJ. DesterkeC. GoldschmidtE. Chadefaux-VekemansB. BonnarmeP. BriozzoP. KopečnýD. PierigèF. MagnaniM. MolliconeR. Haghighi-RadF. Gaston-MathéY. DairouJ. BoucheixC. SaffroyR. Effects in cancer cells of the recombinant l-methionine gamma-lyase from Brevibacterium aurantiacum. Encapsulation in human erythrocytes for sustained l-methionine elimination.J. Pharmacol. Exp. Ther.2019369348950210.1124/jpet.119.25653730940696
     [Google Scholar]
  25. İpekS.L. ÖzdemirM.D. GöktürkD. Cytotoxic effect of L-methioninase from Brevibacterium linens BL2 in combination with etoposide against Glioblastoma cells.Appl. Sci.20231316938210.3390/app13169382
     [Google Scholar]
  26. ForquinM.P. HébertA. RouxA. AubertJ. ProuxC. HeilierJ.F. LandaudS. JunotC. BonnarmeP. Martin-VerstraeteI. Global regulation of the response to sulfur availability in the cheese-related bacterium Brevibacterium aurantiacum.Appl. Environ. Microbiol.20117741449145910.1128/AEM.01708‑1021169450
     [Google Scholar]
  27. SteeleL. MayerL. BerinC.M. Mucosal immunology of tolerance and allergy in the gastrointestinal tract.Immunol. Res.2012541-3758210.1007/s12026‑012‑8308‑422447352
     [Google Scholar]
  28. BergmansH.E. van DieI.M. HoekstraW.P. Transformation in Escherichia coli: Stages in the process.J. Bacteriol.1981146256457010.1128/jb.146.2.564‑570.19817012133
     [Google Scholar]
  29. İpekS.L. Bacterial diversity and lysozyme activity of raw buffalo milk: A case study on milk collection tanks from selected farms.CYTA J. Food2024221242872710.1080/19476337.2024.2428727
     [Google Scholar]
  30. PriyadarshiniS. KansalV.K. Lysozyme activity in buffalo milk: Effect of lactation period, parity, mastitis, season in India, pH and milk processing heat treatment.Asian-Australas. J. Anim. Sci.200215689589910.5713/ajas.2002.895
     [Google Scholar]
  31. El-SayedA.S. ShoumanS.A. NassratH.M. Pharmacokinetics, immunogenicity and anticancer efficiency of Aspergillus flavipes l-methioninase.Enzyme Microb. Technol.201251420021010.1016/j.enzmictec.2012.06.00422883554
     [Google Scholar]
  32. BradfordM.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal. Biochem.1976721-224825410.1016/0003‑2697(76)90527‑3942051
     [Google Scholar]
  33. RepettoG. del PesoA. ZuritaJ.L. Neutral red uptake assay for the estimation of cell viability/cytotoxicity.Nat. Protoc.2008371125113110.1038/nprot.2008.7518600217
     [Google Scholar]
  34. Al-KhedhairyA.A. WahabR. Size-dependent cytotoxic and molecular study of the use of gold nanoparticles against liver cancer cells.Appl. Sci.202212290110.3390/app12020901
     [Google Scholar]
  35. BorenfreundE. PuernerJ.A. Toxicity determined in vitro by morphological alterations and neutral red absorption.Toxicol. Lett.1985242-311912410.1016/0378‑4274(85)90046‑33983963
     [Google Scholar]
  36. MohantyA.K. DilnawazF. MohantyC. SahooS.K. Etoposide-loaded biodegradable amphiphilic methoxy (poly ethylene glycol) and poly (epsilon caprolactone) copolymeric micelles as drug delivery vehicle for cancer therapy.Drug Deliv.201017533034210.3109/1071754100372068820370380
     [Google Scholar]
  37. BarciaJ.J. The Giemsa stain: Its history and applications.Int. J. Surg. Pathol.200715329229610.1177/106689690730223917652540
     [Google Scholar]
  38. MatsudaY. IshiwataT. KawamotoY. KawaharaK. PengW.X. YamamotoT. NaitoZ. Morphological and cytoskeletal changes of pancreatic cancer cells in three-dimensional spheroidal culture.Med. Mol. Morphol.201043421121710.1007/s00795‑010‑0497‑021267697
     [Google Scholar]
  39. AamazadehF. OstadrahimiA. RahbarS.Y. BararJ. Bitter apricot ethanolic extract induces apoptosis through increasing expression of Bax/Bcl-2 ratio and caspase-3 in PANC-1 pancreatic cancer cells.Mol. Biol. Rep.20204731895190410.1007/s11033‑020‑05286‑w32026321
     [Google Scholar]
  40. HanniffyS.B. PhiloM. PeláezC. GassonM.J. RequenaT. Martínez-CuestaM.C. Heterologous production of methionine-γ-lyase from Brevibacterium linens in Lactococcus lactis and formation of volatile sulfur compounds.Appl. Environ. Microbiol.20097582326233210.1128/AEM.02417‑0819251895
     [Google Scholar]
  41. ZhangY. JelleschitzJ. GruneT. ChenW. ZhaoY. JiaM. WangY. LiuZ. HöhnA. Methionine restriction - Association with redox homeostasis and implications on aging and diseases.Redox Biol.20225710246410.1016/j.redox.2022.10246436152485
     [Google Scholar]
  42. MoreheadL.C. GargS. WallisK.F. SimoesC.C. SiegelE.R. TackettA.J. MiousseI.R. Increased response to immune checkpoint inhibitors with dietary methionine restriction in a colorectal cancer model.Cancers20231518446710.3390/cancers1518446737760436
     [Google Scholar]
  43. ChaturvediS. HoffmanR.M. BertinoJ.R. Exploiting methionine restriction for cancer treatment.Biochem. Pharmacol.201815417017310.1016/j.bcp.2018.05.00329733806
     [Google Scholar]
  44. WandersD. HobsonK. JiX. Methionine restriction and cancer biology.Nutrients202012368410.3390/nu1203068432138282
     [Google Scholar]
  45. CavuotoP. FenechM.F. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.Cancer Treat. Rev.201238672673610.1016/j.ctrv.2012.01.00422342103
     [Google Scholar]
  46. CaroP. GomezJ. SanchezI. NaudiA. AyalaV. López-TorresM. PamplonaR. BarjaG. Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria.Rejuvenation Res.200912642143410.1089/rej.2009.090220041736
     [Google Scholar]
  47. NakagawaS. LagiszM. HectorK.L. SpencerH.G. Comparative and meta-analytic insights into life extension via dietary restriction.Aging Cell201211340140910.1111/j.1474‑9726.2012.00798.x22268691
     [Google Scholar]
  48. ZouK. RouskinS. DervishiK. McCormickM.A. SasikumarA. DengC. ChenZ. KaeberleinM. BremR.B. PolymenisM. KennedyB.K. WeissmanJ.S. ZhengJ. OuyangQ. LiH. Life span extension by glucose restriction is abrogated by methionine supplementation: Cross-talk between glucose and methionine and implication of methionine as a key regulator of life span.Sci. Adv.2020632eaba130610.1126/sciadv.aba130632821821
     [Google Scholar]
  49. Solon-BietS.M. McMahonA.C. BallardJ.W.O. RuohonenK. WuL.E. CoggerV.C. WarrenA. HuangX. PichaudN. MelvinR.G. GokarnR. KhalilM. TurnerN. CooneyG.J. SinclairD.A. RaubenheimerD. Le CouteurD.G. SimpsonS.J. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice.Cell Metab.201419341843010.1016/j.cmet.2014.02.00924606899
     [Google Scholar]
  50. PlummerJ.D. JohnsonJ.E. Extension of cellular lifespan by methionine restriction involves alterations in central carbon metabolism and is mitophagy-dependent.Front. Cell Dev. Biol.2019730110.3389/fcell.2019.0030131850341
     [Google Scholar]
  51. GomezJ. Sanchez-RomanI. GomezA. SanchezC. SuarezH. Lopez-TorresM. BarjaG. Methionine and homocysteine modulate the rate of ROS generation of isolated mitochondria in vitro.J. Bioenerg. Biomembr.201143437738610.1007/s10863‑011‑9368‑121748404
     [Google Scholar]
  52. HineC. MitchellJ.R. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway.Exp. Gerontol.201568263210.1016/j.exger.2014.12.01025523462
     [Google Scholar]
  53. ParkhitkoA.A. JouandinP. MohrS.E. PerrimonN. Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species.Aging Cell2019186e1303410.1111/acel.1303431460700
     [Google Scholar]
  54. AokiY. HanQ. KubotaY. MasakiN. ObaraK. TomeY. Oncogenes and methionine addiction of cancer: Role of c-MYC.Cancer Genomics Proteomics202320216517010.21873/cgp.20371
     [Google Scholar]
  55. LauingerL. KaiserP. Sensing and signaling of methionine metabolism.Metabolites20211128310.3390/metabo1102008333572567
     [Google Scholar]
  56. BertinoJ.R. WaudW.R. ParkerW.B. LubinM. Targeting tumors that lack methylthioadenosine phosphorylase (MTAP) activity.Cancer Biol. Ther.201111762763210.4161/cbt.11.7.1494821301207
     [Google Scholar]
  57. SternP.H. WallaceC.D. HoffmanR.M. Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines.J. Cell. Physiol.19841191293410.1002/jcp.10411901066707100
     [Google Scholar]
  58. MechamJ.O. RowitchD. WallaceC.D. SternP.H. HoffmanR.M. The metabolic defect of methionine dependence occurs frequently in human tumor cell lines.Biochem. Biophys. Res. Commun.1983117242943410.1016/0006‑291X(83)91218‑46661235
     [Google Scholar]
  59. GuoH.Y. HerreraH. HoffmanR.M. Unchecked DNA synthesis and blocked cell division induced by methionine deprivation in a human prostate cancer cell line. In Vitro Cell. Dev. Biol.199329535936110.1007/BF026339828314730
     [Google Scholar]
  60. TanY. XuM. HoffmanR.M. Broad selective efficacy of recombinant methioninase and polyethylene glycol-modified recombinant methioninase on cancer cells In vitro.Anticancer Res.20103041041104620530407
     [Google Scholar]
  61. HoffmanR.M. Development of recombinant methioninase to target the general cancer-specific metabolic defect of methionine dependence: A 40-year odyssey.Expert Opin. Biol. Ther.2015151213110.1517/14712598.2015.96305025439528
     [Google Scholar]
  62. DavydovD.Z. MorozovaЕ.А. KomarovaМ.V. AnufrievaN.V. ZavilgelskyG.B. ManukhovI.V. DemidkinaT.V. TreshchalinaЕ.М. PokrovskyV.S. Use of pyridoxine to increase anticacner activity of methionine-gamma-lyase in murine cancer models.Siberian journal of oncology2017165273510.21294/1814‑4861‑2017‑16‑5‑27‑35
     [Google Scholar]
  63. EpnerD.E. MorrowS. WilcoxM. HoughtonJ.L. Nutrient intake and nutritional indexes in adults with metastatic cancer on a phase I clinical trial of dietary methionine restriction.Nutr. Cancer200242215816610.1207/S15327914NC422_212416254
     [Google Scholar]
  64. ThivatE. FargesM.C. BacinF. D’IncanM. Mouret-ReynierM.A. CellarierE. MadelmontJ.C. VassonM.P. CholletP. DurandoX. Phase II trial of the association of a methionine-free diet with cystemustine therapy in melanoma and glioma.Anticancer Res.200929125235524020044642
     [Google Scholar]
  65. DurandoX. FargesM.C. BucE. AbrialC. Petorin-LesensC. GilletB. VassonM.P. PezetD. CholletP. ThivatE. Dietary methionine restriction with FOLFOX regimen as first line therapy of metastatic colorectal cancer: A feasibility study.Oncology2010783-420520910.1159/00031370020424491
     [Google Scholar]
  66. ThivatE. DurandoX. DemidemA. FargesM.C. RappM. CellarierE. GueninS. D’IncanM. VassonM.P. CholletP. A methionine-free diet associated with nitrosourea treatment down-regulates methylguanine-DNA methyl transferase activity in patients with metastatic cancer.Anticancer Res.2007274C2779278317695447
     [Google Scholar]
  67. YanoS. LiS. HanQ. TanY. BouvetM. FujiwaraT. HoffmanR.M. Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity.Oncotarget20145188729873610.18632/oncotarget.236925238266
     [Google Scholar]
  68. HoffmanR.M. JacobsenS.J. Reversible growth arrest in simian virus 40-transformed human fibroblasts.Proc. Natl. Acad. Sci. USA198077127306731010.1073/pnas.77.12.73066261250
     [Google Scholar]
  69. LuS. EpnerD.E. Molecular mechanisms of cell cycle block by methionine restriction in human prostate cancer cells.Nutr. Cancer200038112313010.1207/S15327914NC381_1711341037
     [Google Scholar]
  70. WangS.T. ChenH.W. SheenL.Y. LiiC.K. Methionine and cysteine affect glutathione level, glutathione-related enzyme activities and the expression of glutathione S-transferase isozymes in rat hepatocytes.J. Nutr.1997127112135214110.1093/jn/127.11.21359372907
     [Google Scholar]
  71. KokkinakisD.M. von WronskiM.A. VuongT.H. BrentT.P. ScholdS.C. Regulation of O6-methylguanine-DNA methyltransferase by methionine in human tumour cells.Br. J. Cancer199775677978810.1038/bjc.1997.1419062396
     [Google Scholar]
  72. SatoD. NozakiT. Methionine gamma-lyase: The unique reaction mechanism, physiological roles, and therapeutic applications against infectious diseases and cancers.IUBMB Life200961111019102810.1002/iub.25519859976
     [Google Scholar]
  73. KawaguchiK. MiyakeK. HanQ. LiS. TanY. IgarashiK. KiyunaT. MiyakeM. HiguchiT. OshiroH. ZhangZ. RazmjooeiS. WangsiricharoenS. BouvetM. SinghS.R. UnnoM. HoffmanR.M. Oral recombinant methioninase (o-rMETase) is superior to injectable rMETase and overcomes acquired gemcitabine resistance in pancreatic cancer.Cancer Lett.201843225125910.1016/j.canlet.2018.06.01629928962
     [Google Scholar]
  74. Key statistics for pancreatic cancer.2025Available from: https://www.cancer.org/cancer/types/pancreatic-cancer/about/key-statistics.html
  75. MaebashiM. MiyakeK. YamamotoJ. SaharaK. AkiyamaT. KimuraY. EndoI. Methionine restriction inhibits pancreatic cancer proliferation while suppressing JAK2/STAT3 pathway.Pancreatology202525110811710.1016/j.pan.2024.11.02339668011
     [Google Scholar]
  76. YamamotoJ. MiyakeK. HanQ. TanY. InubushiS. SugisawaN. HiguchiT. TashiroY. NishinoH. HommaY. MatsuyamaR. ChawlaS.P. BouvetM. SinghS.R. EndoI. HoffmanR.M. Oral recombinant methioninase increases TRAIL receptor-2 expression to regress pancreatic cancer in combination with agonist tigatuzumab in an orthotopic mouse model.Cancer Lett.202049217418410.1016/j.canlet.2020.07.03432739322
     [Google Scholar]
  77. KubotaY. AokiY. MasakiN. ObaraK. HamadaK. HanQ. BouvetM. TsunodaT. HoffmanR.M. Methionine restriction of glioma does not induce MGMT and greatly improves temozolomide efficacy in an orthotopic nude-mouse model: A potential curable approach to a clinically-incurable disease.Biochem. Biophys. Res. Commun.202469514941810.1016/j.bbrc.2023.14941838176171
     [Google Scholar]
  78. SatoM. HanQ. MizutaK. MoriR. KangB.M. MorinagaS. KobayashiN. IchikawaY. NakajimaA. HoffmanR.M. Hoffman, R.M. Extensive shrinkage and long-term stable disease in a teenage female patient with high-grade glioma treated with temozolomide and radiation in combination with oral recombinant methioninase and a low-methionine diet. In Vivos20243831459146410.21873/invivo.1359138688589
     [Google Scholar]
  79. ChenZ. Human enzyme-mediated, systemic depletion of methionine for glioblastoma treatment.Doctoral Dissertation2022
     [Google Scholar]
  80. MorinagaS. HanQ. MizutaK. KangB.M. BouvetM. YamamotoN. HayashiK. KimuraH. MiwaS. IgarashiK. HiguchiT. TsuchiyaH. DemuraS. HoffmanR.M. Ivermectin combined with recombinant methioninase (rMETase) synergistically eradicates MiaPaCa-2 pancreatic cancer cells.Anticancer Res.20254519710310.21873/anticanres.1739639740811
     [Google Scholar]
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Recombinant Expression of L-methioninase from Brevibacterium linens and Evaluation of its Anticarcinogenic Properties against MiaPaCa-2 Cells
PPL 32, 451 (2025); https://doi.org/10.2174/0109298665383781250624054915
/content/journals/ppl/10.2174/0109298665383781250624054915
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  • Article Type:     Research Article
Keyword(s): Brevibacterium linens; cancer; etoposide; His-tag elimination; MiaPaCa-2; rBlmet treatment; recombinant methioninase

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