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2000
Volume 32, Issue 32
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a regulator of the cellular antioxidant defense system that plays an important role in reducing the risk of various pathophysiological conditions, including cancer. Targeting Nrf2 presents an attractive therapeutic approach to overcome these challenges and improve cancer treatment outcomes. Nanoparticles, with their unique physicochemical properties, offer several advantages over conventional therapies for targeting Nrf2. These include enhanced stability, improved permeability and retention effect, and precise targeting capabilities. Moreover, delivery systems based on nanotechnology have shown promise in overcoming the limitations of conventional cancer therapies, including ineffective precision targeting and momentous complications. The therapeutic efficacy of Nrf2 inhibitors may be enhanced by using nanoparticles for specific drug targeting and deeper tissue penetration. This involves optimizing nanoparticle formulations, understanding their interactions with the biological environment, and ensuring their safety and biocompatibility. Effective nanoparticle formulations are being developed to transport Nrf2 inhibitors, which can significantly improve treatment outcomes and address the limitations of conventional cancer therapies. Further studies are needed to explore the potential of nanotechnology in targeting Nrf2 for cancer therapeutic purposes.

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References

  1. BrayF. FerlayJ. SoerjomataramI. SiegelR.L. TorreL.A. JemalA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.201868639442410.3322/caac.2149230207593
    [Google Scholar]
  2. JovčevskaI. MuyldermansS. The therapeutic potential of nanobodies.BioDrugs2020341112610.1007/s40259‑019‑00392‑z31686399
    [Google Scholar]
  3. AlfaroukK.O. StockC.M. TaylorS. WalshM. MuddathirA.K. VerduzcoD. BashirA.H.H. MohammedO.Y. ElhassanG.O. HarguindeyS. ReshkinS.J. IbrahimM.E. RauchC. Resistance to cancer chemotherapy: Failure in drug response from ADME to P-gp.Cancer Cell Int.20151517110.1186/s12935‑015‑0221‑126180516
    [Google Scholar]
  4. BaghbanR. RoshangarL. Jahanban-EsfahlanR. SeidiK. Ebrahimi-KalanA. JaymandM. KolahianS. JavaheriT. ZareP. Tumor microenvironment complexity and therapeutic implications at a glance.Cell Commun. Signal.20201815910.1186/s12964‑020‑0530‑432264958
    [Google Scholar]
  5. GavasS. QuaziS. KarpińskiT.M. Nanoparticles for cancer therapy: Current progress and challenges.Nanoscale Res. Lett.202116117310.1186/s11671‑021‑03628‑634866166
    [Google Scholar]
  6. DadwalA. BaldiA. Kumar NarangR. Nanoparticles as carriers for drug delivery in cancer.Artif. Cells Nanomed. Biotechnol.201846S229530510.1080/21691401.2018.1457039
    [Google Scholar]
  7. ThiruvengadamR. VenkidasamyB. SamynathanR. GovindasamyR. ThiruvengadamM. KimJ.H. Association of nanoparticles and Nrf2 with various oxidative stress-mediated diseases.Chem. Biol. Interact.202338011053510.1016/j.cbi.2023.11053537187268
    [Google Scholar]
  8. MurakamiS. MotohashiH. Roles of Nrf2 in cell proliferation and differentiation.Free Radic. Biol. Med.201588Pt B16817810.1016/j.freeradbiomed.2015.06.03026119783
    [Google Scholar]
  9. ShahcheraghiS.H. SalemiF. PeiroviN. AyatollahiJ. AlamW. KhanH. SasoL. Nrf2 regulation by curcumin: Molecular aspects for therapeutic prospects.Molecules202127116710.3390/molecules2701016735011412
    [Google Scholar]
  10. FarkhondehT. FolgadoS.L. Pourbagher-ShahriA.M. AshrafizadehM. SamarghandianS. The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway.Biomed. Pharmacother.202012711023410.1016/j.biopha.2020.11023432559855
    [Google Scholar]
  11. RussoM. SpagnuoloC. RussoG.L. Skalicka-WoźniakK. DagliaM. Sobarzo-SánchezE. NabaviS.F. NabaviS.M. Nrf2 targeting by sulforaphane: A potential therapy for cancer treatment.Crit. Rev. Food Sci. Nutr.20185881391140510.1080/10408398.2016.125998328001083
    [Google Scholar]
  12. BauerA.K. HillT. AlexanderC.M. The involvement of NRF2 in lung cancer.Oxid. Med. Cell Longev.2013201374643210.1155/2013/74643223577226
    [Google Scholar]
  13. SpornM.B. LibyK.T. NRF2 and cancer: The good, the bad and the importance of context.Nat. Rev. Cancer201212856457110.1038/nrc327822810811
    [Google Scholar]
  14. RobertsonH. Dinkova-KostovaA.T. HayesJ.D. NRF2 and the ambiguous consequences of its activation during initiation and the subsequent stages of tumourigenesis.Cancers (Basel)20201212360910.3390/cancers1212360933276631
    [Google Scholar]
  15. NioiP. NguyenT. SherrattP.J. PickettC.B. The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation.Mol. Cell. Biol.20052524108951090610.1128/MCB.25.24.10895‑10906.200516314513
    [Google Scholar]
  16. ZhangJ. HosoyaT. MaruyamaA. NishikawaK. MaherJ.M. OhtaT. MotohashiH. FukamizuA. ShibaharaS. ItohK. YamamotoM. Nrf2 Neh5 domain is differentially utilized in the transactivation of cytoprotective genes.Biochem. J.2007404345946610.1042/BJ2006161117313370
    [Google Scholar]
  17. AlamM.M. OkazakiK. NguyenL.T.T. OtaN. KitamuraH. MurakamiS. ShimaH. IgarashiK. SekineH. MotohashiH. Glucocorticoid receptor signaling represses the antioxidant response by inhibiting histone acetylation mediated by the transcriptional activator NRF2.J. Biol. Chem.2017292187519753010.1074/jbc.M116.77396028314773
    [Google Scholar]
  18. KangJ.S. NamL.B. YooO.K. KeumY.S. Molecular mechanisms and systemic targeting of NRF2 dysregulation in cancer.Biochem. Pharmacol.202017711400210.1016/j.bcp.2020.11400232360363
    [Google Scholar]
  19. WangH. LiuK. GengM. GaoP. WuX. HaiY. LiY. LiY. LuoL. HayesJ.D. WangX.J. TangX. RXRα inhibits the NRF2-ARE signaling pathway through a direct interaction with the Neh7 domain of NRF2.Cancer Res.201373103097310810.1158/0008‑5472.CAN‑12‑338623612120
    [Google Scholar]
  20. MoiP. ChanK. AsunisI. CaoA. KanY.W. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region.Proc. Natl. Acad. Sci. USA199491219926993010.1073/pnas.91.21.99267937919
    [Google Scholar]
  21. SuzukiT. MuramatsuA. SaitoR. IsoT. ShibataT. KuwataK. KawaguchiS. IwawakiT. AdachiS. SudaH. MoritaM. UchidaK. BairdL. YamamotoM. Molecular mechanism of cellular oxidative stress sensing by Keap1.Cell Rep.2019283746758.e410.1016/j.celrep.2019.06.04731315052
    [Google Scholar]
  22. CanningP. CooperC.D.O. KrojerT. MurrayJ.W. PikeA.C.W. ChaikuadA. KeatesT. ThangaratnarajahC. HojzanV. MarsdenB.D. GileadiO. KnappS. von DelftF. BullockA.N. Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases.J. Biol. Chem.2013288117803781410.1074/jbc.M112.43799623349464
    [Google Scholar]
  23. KansanenE. KuosmanenS.M. LeinonenH. LevonenA.L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer.Redox Biol.201311454910.1016/j.redox.2012.10.00124024136
    [Google Scholar]
  24. CleasbyA. YonJ. DayP.J. RichardsonC. TickleI.J. WilliamsP.A. CallahanJ.F. CarrR. ConchaN. KernsJ.K. QiH. SweitzerT. WardP. DaviesT.G. Structure of the BTB domain of Keap1 and its interaction with the triterpenoid antagonist CDDO.PLoS One201496e9889610.1371/journal.pone.009889624896564
    [Google Scholar]
  25. PanieriE. BuhaA. Telkoparan-AkillilarP. CevikD. KouretasD. VeskoukisA. SkaperdaZ. TsatsakisA. WallaceD. SuzenS. SasoL. Potential applications of NRF2 modulators in cancer therapy.Antioxidants20209319310.3390/antiox903019332106613
    [Google Scholar]
  26. CanningP. SorrellF.J. BullockA.N. Structural basis of Keap1 interactions with Nrf2.Free Radic. Biol. Med.201588Pt B10110710.1016/j.freeradbiomed.2015.05.03426057936
    [Google Scholar]
  27. MageshS. ChenY. HuL. Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents.Med. Res. Rev.201232468772610.1002/med.2125722549716
    [Google Scholar]
  28. JaramilloM.C. ZhangD.D. The emerging role of the Nrf2–Keap1 signaling pathway in cancer.Genes Dev.201327202179219110.1101/gad.225680.11324142871
    [Google Scholar]
  29. BairdL. YamamotoM. The molecular mechanisms regulating the KEAP1-NRF2 pathway.Mol. Cell. Biol.20204013e00099-2010.1128/MCB.00099‑2032284348
    [Google Scholar]
  30. Telkoparan-AkillilarP. SuzenS. SasoL. Pharmacological applications of Nrf2 inhibitors as potential antineoplastic drugs.Int. J. Mol. Sci.2019208202510.3390/ijms2008202531022969
    [Google Scholar]
  31. CuadradoA. RojoA.I. WellsG. HayesJ.D. CousinS.P. RumseyW.L. AttucksO.C. FranklinS. LevonenA.L. KenslerT.W. Dinkova-KostovaA.T. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases.Nat. Rev. Drug Discov.201918429531710.1038/s41573‑018‑0008‑x30610225
    [Google Scholar]
  32. LiouG.Y. StorzP. Reactive oxygen species in cancer.Free Radic. Res.201044547949610.3109/1071576100366755420370557
    [Google Scholar]
  33. KaramZ.M. Baba SalariM. Anjom ShoaaA. Dehghan KouhestaniS. Bahram NejadA. AshourzadehS. ZangouyeeM.R. BazrafshaniM.R. Impact of oxidative stress SNPs on sperm DNA damage and male infertility in a south-east Iranian population.Reprod. Fertil. Dev.2022348633643https://pubmed.ncbi.nlm.nih.gov/35361312/10.1071/RD2130535361312
    [Google Scholar]
  34. WuS. LuH. BaiY. Nrf2 in cancers: A double-edged sword.Cancer Med.2019852252226710.1002/cam4.210130929309
    [Google Scholar]
  35. BirbenE. SahinerU.M. SackesenC. ErzurumS. KalayciO. Oxidative stress and antioxidant defense.World Allergy Organ. J.20125191910.1097/WOX.0b013e318243961323268465
    [Google Scholar]
  36. Vargas-MendozaN. Morales-GonzálezÁ. Madrigal-SantillánE.O. Madrigal-BujaidarE. Álvarez-GonzálezI. García-MeloL.F. Anguiano-RobledoL. Fregoso-AguilarT. Morales-GonzalezJ.A. Antioxidant and adaptative response mediated by Nrf2 during physical exercise.Antioxidants20198619610.3390/antiox806019631242588
    [Google Scholar]
  37. DeBlasiJ.M. DeNicolaG.M. Dissecting the crosstalk between NRF2 signaling and metabolic processes in cancer.Cancers (Basel)20201210302310.3390/cancers1210302333080927
    [Google Scholar]
  38. KitamuraH. MotohashiH. NRF2 addiction in cancer cells.Cancer Sci.2018109490091110.1111/cas.1353729450944
    [Google Scholar]
  39. TaoS. Rojo de la VegaM. ChapmanE. OoiA. ZhangD.D. The effects of NRF2 modulation on the initiation and progression of chemically and genetically induced lung cancer.Mol. Carcinog.201857218219210.1002/mc.2274528976703
    [Google Scholar]
  40. SatohH. MoriguchiT. TakaiJ. EbinaM. YamamotoM. Nrf2 prevents initiation but accelerates progression through the Kras signaling pathway during lung carcinogenesis.Cancer Res.201373134158416810.1158/0008‑5472.CAN‑12‑449923610445
    [Google Scholar]
  41. SatohH. MoriguchiT. SaigusaD. BairdL. YuL. RokutanH. IgarashiK. EbinaM. ShibataT. YamamotoM. NRF2 intensifies host defense systems to prevent lung carcinogenesis, but after tumor initiation accelerates malignant cell growth.Cancer Res.201676103088309610.1158/0008‑5472.CAN‑15‑158427020858
    [Google Scholar]
  42. VomundS. SchäferA. ParnhamM. BrüneB. Von KnethenA. Nrf2, the master regulator of anti-oxidative responses.Int. J. Mol. Sci.20171812277210.3390/ijms1812277229261130
    [Google Scholar]
  43. ShawP. ChattopadhyayA. Nrf2–ARE signaling in cellular protection: Mechanism of action and the regulatory mechanisms.J. Cell. Physiol.202023543119313010.1002/jcp.2921931549397
    [Google Scholar]
  44. JaganjacM. MilkovicL. SunjicS.B. ZarkovicN. The NRF2, thioredoxin, and glutathione system in tumorigenesis and anticancer therapies.Antioxidants2020911115110.3390/antiox911115133228209
    [Google Scholar]
  45. MaQ. Role of nrf2 in oxidative stress and toxicity.Annu. Rev. Pharmacol. Toxicol.201353140142610.1146/annurev‑pharmtox‑011112‑14032023294312
    [Google Scholar]
  46. EnomotoA. ItohK. NagayoshiE. HarutaJ. KimuraT. O’ConnorT. HaradaT. YamamotoM. High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes.Toxicol. Sci.200159116917710.1093/toxsci/59.1.16911134556
    [Google Scholar]
  47. OkawaH. MotohashiH. KobayashiA. AburataniH. KenslerT.W. YamamotoM. Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity.Biochem. Biophys. Res. Commun.20063391798810.1016/j.bbrc.2005.10.18516293230
    [Google Scholar]
  48. FrohlichD.A. McCabeM.T. ArnoldR.S. DayM.L. The role of Nrf2 in increased reactive oxygen species and DNA damage in prostate tumorigenesis.Oncogene200827314353436210.1038/onc.2008.7918372916
    [Google Scholar]
  49. BaeI. FanS. MengQ. RihJ.K. KimH.J. KangH.J. XuJ. GoldbergI.D. JaiswalA.K. RosenE.M. BRCA1 induces antioxidant gene expression and resistance to oxidative stress.Cancer Res.200464217893790910.1158/0008‑5472.CAN‑04‑111915520196
    [Google Scholar]
  50. Rojo de la VegaM. ChapmanE. ZhangD.D. NRF2 and the hallmarks of cancer.Cancer Cell2018341214310.1016/j.ccell.2018.03.02229731393
    [Google Scholar]
  51. GhareghomiS. Habibi-RezaeiM. AreseM. SasoL. Moosavi-MovahediA.A. Nrf2 modulation in breast cancer.Biomedicines20221010266810.3390/biomedicines1010266836289931
    [Google Scholar]
  52. SinghB. BhatN.K. BhatH.K. Induction of NAD(P)H-quinone oxidoreductase 1 by antioxidants in female ACI rats is associated with decrease in oxidative DNA damage and inhibition of estrogen-induced breast cancer.Carcinogenesis201233115616310.1093/carcin/bgr23722072621
    [Google Scholar]
  53. LiuF. IchiharaS. ValentineW.M. ItohK. YamamotoM. Sheik MohideenS. KitohJ. IchiharaG. Increased susceptibility of Nrf2-null mice to 1-bromopropane-induced hepatotoxicity.Toxicol. Sci.2010115259660610.1093/toxsci/kfq07520211940
    [Google Scholar]
  54. WangJ. KonishiT. Nuclear factor (erythroid-derived 2)- like 2 antioxidative response mitigates cytoplasmic radiation-induced DNA double-strand breaks.Cancer Sci.2019110268669610.1111/cas.1391630561156
    [Google Scholar]
  55. SatohH. MoriguchiT. TaguchiK. TakaiJ. MaherJ.M. SuzukiT. WinnardP.T.Jr RamanV. EbinaM. NukiwaT. YamamotoM. Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung.Carcinogenesis201031101833184310.1093/carcin/bgq10520513672
    [Google Scholar]
  56. MoonE.J. GiacciaA. Dual roles of NRF2 in tumor prevention and progression: Possible implications in cancer treatment.Free Radic. Biol. Med.20157929229910.1016/j.freeradbiomed.2014.11.00925458917
    [Google Scholar]
  57. HayashiM. KugaA. SuzukiM. PandaH. KitamuraH. MotohashiH. YamamotoM. Microenvironmental activation of Nrf2 restricts the progression of Nrf2-activated malignant tumors.Cancer Res.202080163331334410.1158/0008‑5472.CAN‑19‑288832636316
    [Google Scholar]
  58. YuW. TuY. LongZ. LiuJ. KongD. PengJ. Reactive oxygen species bridge the gap between chronic inflammation and tumor development.Oxid. Med. Cell Longev.20222022260692810.1155/2022/260692835799889
    [Google Scholar]
  59. SahaS. ButtariB. PanieriE. ProfumoE. SasoL. An overview of Nrf2 signaling pathway and its role in inflammation.Molecules20202522547410.3390/molecules2522547433238435
    [Google Scholar]
  60. KunduJ.K. SurhY.J. Nrf2-Keap1 signaling as a potential target for chemoprevention of inflammation-associated carcinogenesis.Pharm. Res.2010276999101310.1007/s11095‑010‑0096‑820354764
    [Google Scholar]
  61. Fuertes-AgudoM. Luque-TévarM. CucarellaC. Martín-SanzP. CasadoM. Advances in understanding the role of NRF2 in liver pathophysiology and its relationship with hepatic-specific Cyclooxygenase-2 expression.Antioxidants2023128149110.3390/antiox1208149137627486
    [Google Scholar]
  62. GlorieuxC. EnríquezC. GonzálezC. Aguirre-MartínezG. Buc CalderonP. The multifaceted roles of NRF2 in Cancer: Friend or foe?Antioxidants20241317010.3390/antiox1301007038247494
    [Google Scholar]
  63. LeeI.T. LuoS.F. LeeC.W. WangS.W. LinC.C. ChangC.C. ChenY.L. ChauL.Y. YangC.M. Overexpression of HO-1 protects against TNF-α-mediated airway inflammation by down-regulation of TNFR1-dependent oxidative stress.Am. J. Pathol.2009175251953210.2353/ajpath.2009.09001619608869
    [Google Scholar]
  64. Young BangS. KimJ.H. KimH.Y. Ji LeeY. Young ParkS. Joon LeeS. KimY. Achyranthes japonica exhibits anti-inflammatory effect via NF-κB suppression and HO-1 induction in macrophages.J. Ethnopharmacol.2012144110911710.1016/j.jep.2012.08.03722974544
    [Google Scholar]
  65. DuranteW. Protective role of heme oxygenase-1 against inflammation in atherosclerosis.Front Biosci. (Landmark Ed)20111662372238810.2741/386021622183
    [Google Scholar]
  66. EmanueleS. CelesiaA. D’AnneoA. LauricellaM. CarlisiD. De BlasioA. GiulianoM. The good and bad of Nrf2: An update in cancer and new perspectives in COVID-19.Int. J. Mol. Sci.20212215796310.3390/ijms2215796334360732
    [Google Scholar]
  67. ZhouR. TardivelA. ThorensB. ChoiI. TschoppJ. Thioredoxin-interacting protein links oxidative stress to inflammasome activation.Nat. Immunol.201011213614010.1038/ni.183120023662
    [Google Scholar]
  68. Buelna-ChontalM. ZazuetaC. Redox activation of Nrf2 & NF-κB: A double end sword?Cell. Signal.201325122548255710.1016/j.cellsig.2013.08.00723993959
    [Google Scholar]
  69. TaniguchiK. KarinM. NF-κB, inflammation, immunity and cancer: Coming of age.Nat. Rev. Immunol.201818530932410.1038/nri.2017.14229379212
    [Google Scholar]
  70. ZhangD. RennhackJ. AndrechekE.R. RockwellC.E. LibyK.T. Identification of an unfavorable immune signature in advanced lung tumors from Nrf2-deficient mice.Antioxid. Redox Signal.201829161535155210.1089/ars.2017.720129634345
    [Google Scholar]
  71. NamL.B. KeumY.S. Binding partners of NRF2: Functions and regulatory mechanisms.Arch. Biochem. Biophys.201967810818410.1016/j.abb.2019.10818431733215
    [Google Scholar]
  72. QinS. JiangC. GaoJ. Transcriptional factor Nrf2 is essential for aggresome formation during proteasome inhibition.Biomed. Rep.201911624125210.3892/br.2019.124731798869
    [Google Scholar]
  73. RyuD. LeeJ.H. KwakM.K. NRF2 level is negatively correlated with TGF-β1-induced lung cancer motility and migration via NOX4-ROS signaling.Arch. Pharm. Res.202043121297131010.1007/s12272‑020‑01298‑z33242180
    [Google Scholar]
  74. ChenL.H. LiaoC.Y. LaiL.C. TsaiM.H. ChuangE.Y. Semaphorin 6A attenuates the migration capability of lung cancer cells via the NRF2/HMOX1 axis.Sci. Rep.2019911330210.1038/s41598‑019‑49874‑831527696
    [Google Scholar]
  75. LinL. WuQ. LuF. LeiJ. ZhouY. LiuY. ZhuN. YuY. NingZ. SheT. HuM. Nrf2 signaling pathway: Current status and potential therapeutic targetable role in human cancers.Front. Oncol.202313118407910.3389/fonc.2023.118407937810967
    [Google Scholar]
  76. DeNicolaG.M. KarrethF.A. HumptonT.J. GopinathanA. WeiC. FreseK. MangalD. YuK.H. YeoC.J. CalhounE.S. ScrimieriF. WinterJ.M. HrubanR.H. Iacobuzio-DonahueC. KernS.E. BlairI.A. TuvesonD.A. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis.Nature2011475735410610910.1038/nature1018921734707
    [Google Scholar]
  77. YooN.J. KimH.R. KimY.R. AnC.H. LeeS.H. Somatic mutations of the KEAP1 gene in common solid cancers.Histopathology201260694395210.1111/j.1365‑2559.2012.04178.x22348534
    [Google Scholar]
  78. HanadaN. TakahataT. ZhouQ. YeX. SunR. ItohJ. IshiguroA. KijimaH. MimuraJ. ItohK. FukudaS. SaijoY. Methylation of the KEAP1 gene promoter region in human colorectal cancer.BMC Cancer20121216610.1186/1471‑2407‑12‑6622325485
    [Google Scholar]
  79. YuH.A. SuzawaK. JordanE. ZehirA. NiA. KimR. KrisM.G. HellmannM.D. LiB.T. SomwarR. SolitD.B. BergerM.F. ArcilaM. RielyG.J. LadanyiM. Concurrent alterations in EGFR-mutant lung cancers associated with resistance to EGFR kinase inhibitors and characterization of MTOR as a mediator of resistance.Clin. Cancer Res.201824133108311810.1158/1078‑0432.CCR‑17‑296129530932
    [Google Scholar]
  80. LeeS. HuL. Nrf2 activation through the inhibition of Keap1–Nrf2 protein–protein interaction.Med. Chem. Res.202029584686710.1007/s00044‑020‑02539‑y32390710
    [Google Scholar]
  81. CamiñaN. PenningT.M. Genetic and epigenetic regulation of the NRF2-KEAP1 pathway in human lung cancer.Br. J. Cancer202212691244125210.1038/s41416‑021‑01642‑034845361
    [Google Scholar]
  82. AdamJ. HatipogluE. O’FlahertyL. TernetteN. SahgalN. LockstoneH. BabanD. NyeE. StampG.W. WolhuterK. StevensM. FischerR. CarmelietP. MaxwellP.H. PughC.W. FrizzellN. SogaT. KesslerB.M. El-BahrawyM. RatcliffeP.J. PollardP.J. Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: Roles for fumarate in KEAP1 succination and Nrf2 signaling.Cancer Cell201120452453710.1016/j.ccr.2011.09.00622014577
    [Google Scholar]
  83. NabihH.K. Crosstalk between NRF2 and Dicer through metastasis regulating MicroRNAs; mir-34a, mir-200 family and mir-103/107 family.Arch. Biochem. Biophys.202068610832610.1016/j.abb.2020.10832632142889
    [Google Scholar]
  84. AyersD. BaronB. HunterT. miRNA influences in NRF2 pathway interactions within cancer models.J. Nucleic Acids.2015201514363610.1155/2015/14363626345522
    [Google Scholar]
  85. NgoV. DuennwaldM.L. Nrf2 and oxidative stress: A general overview of mechanisms and implications in human disease.Antioxidants20221112234510.3390/antiox1112234536552553
    [Google Scholar]
  86. GuoY. YuS. ZhangC. KongA.N.T. Epigenetic regulation of Keap1-Nrf2 signaling.Free Radic. Biol. Med.201588Pt B33734910.1016/j.freeradbiomed.2015.06.01326117320
    [Google Scholar]
  87. HayesJ.D. McMahonM. NRF2 and KEAP1 mutations: Permanent activation of an adaptive response in cancer.Trends Biochem. Sci.200934417618810.1016/j.tibs.2008.12.00819321346
    [Google Scholar]
  88. DodsonM. de la VegaM.R. CholaniansA.B. SchmidlinC.J. ChapmanE. ZhangD.D. Modulating NRF2 in disease: Timing is everything.Annu. Rev. Pharmacol. Toxicol.201959155557510.1146/annurev‑pharmtox‑010818‑02185630256716
    [Google Scholar]
  89. KatsuragiY. IchimuraY. KomatsuM. Regulation of the Keap1–Nrf2 pathway by p62/SQSTM1.Curr. Opin. Toxicol.20161546110.1016/j.cotox.2016.09.005
    [Google Scholar]
  90. KaragiannisD. WuW. LiA. HayashiM. ChenX. YipM. MangipudyV. XuX. Sánchez-RiveraF.J. Soto-FelicianoY.M. YeJ. PapagiannakopoulosT. LuC. Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors.Cell Rep.202443111362910.1016/j.celrep.2023.11362938165806
    [Google Scholar]
  91. WangY.Y. ChenJ. LiuX.M. ZhaoR. ZheH. Nrf2- mediated metabolic reprogramming in cancer.Oxid. Med. Cell Longev.20182018930409110.1155/2018/930409129670683
    [Google Scholar]
  92. ZimtaA.A. CenariuD. IrimieA. MagdoL. NabaviS.M. AtanasovA.G. Berindan-NeagoeI. The role of Nrf2 activity in cancer development and progression.Cancers (Basel)20191111175510.3390/cancers1111175531717324
    [Google Scholar]
  93. WangB. TengY. LiuQ. MicroRNA-153 regulates NRF2 expression and is associated with breast carcinogenesis.Clin. Lab.20166201+02/2016394710.7754/Clin.Lab.2015.15051827012032
    [Google Scholar]
  94. Samarghandian, S.; Azimi-Nezhad, M.; Borji, A.; Farkhondeh, T. Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state. Phytotherapy Res. 2016, 30(8), 1345-53. 10.1186/1471‑2407‑13‑38023937621
  95. PanH. WangH. ZhuL. MaoL. QiaoL. SuX. The role of Nrf2 in migration and invasion of human glioma cell U251.World Neurosurg.2013803-436337010.1016/j.wneu.2011.06.06322120303
    [Google Scholar]
  96. TertilM. GoldaS. SkrzypekK. FlorczykU. WeglarczykK. KotlinowskiJ. MaleszewskaM. CzaudernaS. PichonC. KiedaC. JozkowiczA. DulakJ. Nrf2-heme oxygenase-1 axis in mucoepidermoid carcinoma of the lung: Antitumoral effects associated with down-regulation of matrix metalloproteinases.Free Radic. Biol. Med.20158914715710.1016/j.freeradbiomed.2015.08.00426393425
    [Google Scholar]
  97. MoubarakM.M. ZottolaA.C.P. LarrieuC.M. CuvellierS. DaubonT. MartinO.C.B. Exploring the multifaceted role of NRF2 in brain physiology and cancer: A comprehensive review.Neurooncol. Adv.200461vdad16010.1093/noajnl/vdad16038221979
    [Google Scholar]
  98. WuK.C. CuiJ.Y. KlaassenC.D. Beneficial role of Nrf2 in regulating NADPH generation and consumption.Toxicol. Sci.2011123259060010.1093/toxsci/kfr18321775727
    [Google Scholar]
  99. MalhotraD. Portales-CasamarE. SinghA. SrivastavaS. ArenillasD. HappelC. ShyrC. WakabayashiN. KenslerT.W. WassermanW.W. BiswalS. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis.Nucleic Acids Res.201038175718573410.1093/nar/gkq21220460467
    [Google Scholar]
  100. SongM.Y. LeeD.Y. ChunK.S. KimE.H. The role of NRF2/KEAP1 signaling pathway in cancer metabolism.Int. J. Mol. Sci.2021229437610.3390/ijms2209437633922165
    [Google Scholar]
  101. RaghunathA. SundarrajK. ArfusoF. SethiG. PerumalE. Dysregulation of Nrf2 in hepatocellular carcinoma: Role in cancer progression and chemoresistance.Cancers (Basel)2018101248110.3390/cancers1012048130513925
    [Google Scholar]
  102. ChioI.I.C. JafarnejadS.M. Ponz-SarviseM. ParkY. RiveraK. PalmW. WilsonJ. SangarV. HaoY. ÖhlundD. WrightK. FilippiniD. LeeE.J. Da SilvaB. SchoepferC. WilkinsonJ.E. BuscagliaJ.M. DeNicolaG.M. TiriacH. HammellM. CrawfordH.C. SchmidtE.E. ThompsonC.B. PappinD.J. SonenbergN. TuvesonD.A. NRF2 promotes tumor maintenance by modulating mRNA translation in pancreatic cancer.Cell2016166496397610.1016/j.cell.2016.06.05627477511
    [Google Scholar]
  103. FrancoR. CidlowskiJ.A. Apoptosis and glutathione: Beyond an antioxidant.Cell Death Differ.200916101303131410.1038/cdd.2009.10719662025
    [Google Scholar]
  104. WildA.C. MoinovaH.R. MulcahyR.T. Regulation of γ-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2.J. Biol. Chem.199927447336273363610.1074/jbc.274.47.3362710559251
    [Google Scholar]
  105. FaraonioR. VergaraP. Di MarzoD. PierantoniM.G. NapolitanoM. RussoT. CiminoF. p53 suppresses the Nrf2-dependent transcription of antioxidant response genes.J. Biol. Chem.200628152397763978410.1074/jbc.M60570720017077087
    [Google Scholar]
  106. ElsbyR. KitteringhamN.R. GoldringC.E. LovattC.A. ChamberlainM. HendersonC.J. WolfC.R. ParkB.K. Increased constitutive c-Jun N-terminal kinase signaling in mice lacking glutathione S-transferase Pi.J. Biol. Chem.200327825222432224910.1074/jbc.M30121120012646564
    [Google Scholar]
  107. JainA. LamarkT. SjøttemE. Bowitz LarsenK. Atesoh AwuhJ. ØvervatnA. McMahonM. HayesJ.D. JohansenT. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription.J. Biol. Chem.201028529225762259110.1074/jbc.M110.11897620452972
    [Google Scholar]
  108. RushworthS.A. MacEwanD.J. HO-1 underlies resistance of AML cells to TNF-induced apoptosis.Blood200811173793380110.1182/blood‑2007‑07‑10404218202225
    [Google Scholar]
  109. BialkP. WangY. BanasK. KmiecE.B. Functional gene knockout of NRF2 increases chemosensitivity of human lung cancer A549 cells in vitro and in a xenograft mouse model.Mol. Ther. Oncolytics201811758910.1016/j.omto.2018.10.00230505938
    [Google Scholar]
  110. LiuJ. QinX. MaW. JiaS. ZhangX. YangX. PanD. JinF. Corilagin induces apoptosis and autophagy in NRF2-addicted U251 glioma cell line.Mol. Med. Rep.202123532010.3892/mmr.2021.1195933760110
    [Google Scholar]
  111. ConteA. ValenteV. PaladinoS. PierantoniG.M. HIPK2 in cancer biology and therapy: Recent findings and future perspectives.Cell. Signal.202310111049110.1016/j.cellsig.2022.11049136241057
    [Google Scholar]
  112. LiuY. YangH. WenY. LiB. ZhaoY. XingJ. ZhangM. ChenY. Nrf2 inhibits periodontal ligament stem cell apoptosis under excessive oxidative stress.Int. J. Mol. Sci.2017185107610.3390/ijms1805107628513573
    [Google Scholar]
  113. KhdairA. Di Chen PatilY. MaL. DouQ.P. ShekharM.P.V. PanyamJ. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.J. Control. Release2010141213714410.1016/j.jconrel.2009.09.00419751777
    [Google Scholar]
  114. KimS.K. YangJ.W. KimM.R. RohS.H. KimH.G. LeeK.Y. JeongH.G. KangK.W. Increased expression of Nrf2/ARE-dependent anti-oxidant proteins in tamoxifen-resistant breast cancer cells.Free Radic. Biol. Med.200845453754610.1016/j.freeradbiomed.2008.05.01118539158
    [Google Scholar]
  115. ChoJ.M. ManandharS. LeeH.R. ParkH.M. KwakM.K. Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: Implication to cancer cell resistance.Cancer Lett.20082601-29610810.1016/j.canlet.2007.10.02218036733
    [Google Scholar]
  116. BanN. TakahashiY. TakayamaT. KuraT. KatahiraT. SakamakiS. NiitsuY. Transfection of glutathione S-transferase (GST)-π antisense complementary DNA increases the sensitivity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide.Cancer Res.19965615357735828758929
    [Google Scholar]
  117. KaurT. KhandujaK.L. GuptaR. GuptaN.M. VaipheiK. Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinoma.Dis. Esophagus200821210310710.1111/j.1442‑2050.2007.00742.x18269643
    [Google Scholar]
  118. AleksunesL.M. SlittA.L. MaherJ.M. AugustineL.M. GoedkenM.J. ChanJ.Y. CherringtonN.J. KlaassenC.D. ManautouJ.E. Induction of Mrp3 and Mrp4 transporters during acetaminophen hepatotoxicity is dependent on Nrf2.Toxicol. Appl. Pharmacol.20082261748310.1016/j.taap.2007.08.02217935745
    [Google Scholar]
  119. RekaA.K. GoswamiM.T. KrishnapuramR. StandifordT.J. KeshamouniV.G. Molecular cross-regulation between PPAR-γ and other signaling pathways: Implications for lung cancer therapy.Lung Cancer201172215415910.1016/j.lungcan.2011.01.01921354647
    [Google Scholar]
  120. BlanpainC. MohrinM. SotiropoulouP.A. PasseguéE. DNA-damage response in tissue-specific and cancer stem cells.Cell Stem Cell201181162910.1016/j.stem.2010.12.01221211780
    [Google Scholar]
  121. HallisS.P. KimJ.M. KwakM.K. Emerging role of NRF2 Signaling in cancer stem cell phenotype.Mol. Cells202346315316410.14348/molcells.2023.219636994474
    [Google Scholar]
  122. ZhangJ. XuH.X. ZhuJ.Q. DouY.X. XianY.F. LinZ.X. Natural Nrf2 inhibitors: A review of their potential for cancer treatment.Int. J. Biol. Sci.202319103029304110.7150/ijbs.8240137416770
    [Google Scholar]
  123. JayakumarS. KunwarA. SandurS.K. PandeyB.N. ChaubeyR.C. Differential response of DU145 and PC3 prostate cancer cells to ionizing radiation: Role of reactive oxygen species, GSH and Nrf2 in radiosensitivity.Biochim. Biophys. Acta, Gen. Subj.20141840148549410.1016/j.bbagen.2013.10.00624121106
    [Google Scholar]
  124. LeeS. LimM.J. KimM.H. YuC.H. YunY.S. AhnJ. SongJ.Y. An effective strategy for increasing the radiosensitivity of human lung cancer cells by blocking Nrf2-dependent antioxidant responses.Free Radic. Biol. Med.201253480781610.1016/j.freeradbiomed.2012.05.03822684019
    [Google Scholar]
  125. Samarghandian, S.; Shoshtari, M.E.; Sargolzaei, J.; Hossinimoghadam, H.; Farahzad, J.A. Anti-tumor activity of safranal against neuroblastoma cells. Pharmacognosy Magazine. 2014, 10(Suppl 2), S419. 10.1016/S1535‑6108(04)00115‑115144951
  126. NairS. DohS.T. ChanJ.Y. KongA-N. CaiL. Regulatory potential for concerted modulation of Nrf2- and Nfkb1-mediated gene expression in inflammation and carcinogenesis.Br. J. Cancer200899122070208210.1038/sj.bjc.660470319050705
    [Google Scholar]
  127. SinghA. BodasM. WakabayashiN. BunzF. BiswalS. Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance.Antioxid. Redox Signal.201013111627163710.1089/ars.2010.321920446773
    [Google Scholar]
  128. HeF. AntonucciL. KarinM. NRF2 as a regulator of cell metabolism and inflammation in cancer.Carcinogenesis202041440541610.1093/carcin/bgaa03932347301
    [Google Scholar]
  129. FuJ. XiongZ. HuangC. LiJ. YangW. HanY. PaiboonrungruanC. MajorM.B. ChenK.N. KangX. ChenX. Hyperactivity of the transcription factor Nrf2 causes metabolic reprogramming in mouse esophagus.J. Biol. Chem.2019294132734010.1074/jbc.RA118.00596330409900
    [Google Scholar]
  130. SinghA. HappelC. MannaS.K. Acquaah-MensahG. CarrereroJ. KumarS. NasipuriP. KrauszK.W. WakabayashiN. DewiR. BorosL.G. GonzalezF.J. GabrielsonE. WongK.K. GirnunG. BiswalS. Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis.J. Clin. Invest.201312372921293410.1172/JCI6635323921124
    [Google Scholar]
  131. ZhangH.S. ZhangZ.G. DuG.Y. SunH.L. LiuH.Y. ZhouZ. GouX.M. WuX.H. YuX.Y. HuangY.H. Nrf2 promotes breast cancer cell migration via up-regulation of G6PD/HIF-1α/Notch1 axis.J. Cell. Mol. Med.20192353451346310.1111/jcmm.1424130809937
    [Google Scholar]
  132. MitsuishiY. TaguchiK. KawataniY. ShibataT. NukiwaT. AburataniH. YamamotoM. MotohashiH. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming.Cancer Cell2012221667910.1016/j.ccr.2012.05.01622789539
    [Google Scholar]
  133. ZhaoJ. LinX. MengD. ZengL. ZhuangR. HuangS. LvW. HuJ. Nrf2 mediates metabolic reprogramming in non-small cell lung cancer.Front. Oncol.20201057831510.3389/fonc.2020.57831533324555
    [Google Scholar]
  134. Sánchez-OrtegaM. CarreraA.C. GarridoA. Role of NRF2 in lung cancer.Cells2021108187910.3390/cells1008187934440648
    [Google Scholar]
  135. SamanH. RazaS.S. UddinS. RasulK. Inducing angiogenesis, a key step in cancer vascularization, and treatment approaches.Cancers (Basel)2020125117210.3390/cancers1205117232384792
    [Google Scholar]
  136. HanahanD. WeinbergR.A. Hallmarks of cancer: The next generation.Cell2011144564667410.1016/j.cell.2011.02.01321376230
    [Google Scholar]
  137. TothR. WarfelN. Strange bedfellows: nuclear factor, erythroid 2-like 2 (Nrf2) and hypoxia-inducible factor 1 (HIF-1) in tumor hypoxia.Antioxidants2017622710.3390/antiox602002728383481
    [Google Scholar]
  138. HuangY. YangY. XuY. MaQ. GuoF. ZhaoY. TaoY. LiM. GuoJ. Nrf2/HO-1 axis regulates the angiogenesis of gastric cancer via targeting VEGF.Cancer Manag. Res.2021133155316910.2147/CMAR.S29246133889021
    [Google Scholar]
  139. JiX. WangH. ZhuJ. ZhuL. PanH. LiW. ZhouY. CongZ. YanF. ChenS. Knockdown of Nrf2 suppresses glioblastoma angiogenesis by inhibiting hypoxia-induced activation of HIF-1α.Int. J. Cancer2014135357458410.1002/ijc.2869924374745
    [Google Scholar]
  140. KimT.H. HurE. KangS.J. KimJ.A. ThapaD. LeeY.M. KuS.K. JungY. KwakM.K. NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1α.Cancer Res.20117162260227510.1158/0008‑5472.CAN‑10‑300721278237
    [Google Scholar]
  141. KozakowskaM. Dobrowolska-GlazarB. OkońK. JózkowiczA. DobrowolskiZ. DulakJ. Preliminary analysis of the expression of selected proangiogenic and antioxidant genes and microRNAs in patients with non-muscle-invasive bladder cancer.J. Clin. Med.2016532910.3390/jcm503002926927195
    [Google Scholar]
  142. OhE.T. KimJ. KimJ.M. KimS.J. LeeJ.S. HongS.S. GoodwinJ. RuthenborgR.J. JungM.G. LeeH.J. LeeC.H. ParkE.S. KimC. ParkH.J. NQO1 inhibits proteasome-mediated degradation of HIF-1α.Nat. Commun.2016711359310.1038/ncomms1359327966538
    [Google Scholar]
  143. CastanedaM. den HollanderP. KuburichN.A. RosenJ.M. ManiS.A. Mechanisms of cancer metastasis.Semin. Cancer Biol.871731202210.1016/j.semcancer.2022.10.00636354098
    [Google Scholar]
  144. KumarH. KumarR.M. BhattacharjeeD. SomannaP. JainV. Role of Nrf2 signaling cascade in breast cancer: Strategies and treatment.Front. Pharmacol.20221372007610.3389/fphar.2022.72007635571115
    [Google Scholar]
  145. ZhangC. WangH.J. BaoQ.C. WangL. GuoT.K. ChenW.L. XuL.L. ZhouH.S. BianJ.L. YangY.R. SunH.P. XuX.L. YouQ.D. NRF2 promotes breast cancer cell proliferation and metastasis by increasing RhoA/ROCK pathway signal transduction.Oncotarget2016745735937360610.18632/oncotarget.1243527713154
    [Google Scholar]
  146. ZhaoQ. MaoA. GuoR. ZhangL. YanJ. SunC. TangJ. YeY. ZhangY. ZhangH. Suppression of radiation-induced migration of non-small cell lung cancer through inhibition of Nrf2-Notch axis.Oncotarget2017822366033661310.18632/oncotarget.1662228402268
    [Google Scholar]
  147. AdeshakinF.O. AdeshakinA.O. AfolabiL.O. YanD. ZhangG. WanX. Mechanisms for modulating anoikis resistance in cancer and the relevance of metabolic reprogramming.Front. Oncol.20211162657710.3389/fonc.2021.62657733854965
    [Google Scholar]
  148. XueM. RabbaniN. MomijiH. ImbasiP. AnwarM.M. KitteringhamN. ParkB.K. SoumaT. MoriguchiT. YamamotoM. ThornalleyP.J. Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation.Biochem. J.2012443121322210.1042/BJ2011164822188542
    [Google Scholar]
  149. GureevA.P. ShaforostovaE.A. PopovV.N. Regulation of mitochondrial biogenesis as a way for active longevity: Interaction between the Nrf2 and PGC-1α signaling pathways.Front. Genet.20191043510.3389/fgene.2019.0043531139208
    [Google Scholar]
  150. MirS. Ormsbee GoldenB.D. GriessB.J. VengojiR. TomE. KosmacekE.A. Oberley-DeeganR.E. TalmonG.A. BandV. Teoh-FitzgeraldM.L.T. Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction.Breast Cancer Res.20222414810.1186/s13058‑022‑01548‑635836253
    [Google Scholar]
  151. BlahaC.S. RamakrishnanG. JeonS.M. NogueiraV. RhoH. KangS. BhaskarP. TerryA.R. AissaA.F. FrolovM.V. PatraK.C. Brooks RobeyR. HayN. A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis.Nat. Commun.202213189910.1038/s41467‑022‑28440‑335173161
    [Google Scholar]
  152. LiR. ZengX. YangM. FengJ. XuX. BaoL. YeT. WangX. XueB. HuangY. Antidiabetic DPP-4 inhibitors reprogram tumor microenvironment that facilitates murine breast cancer metastasis through interaction with cancer cells via a ROS–NF-кB–NLRP3 axis.Front. Oncol.20211172804710.3389/fonc.2021.72804734631556
    [Google Scholar]
  153. SutradharK.B. AminM.L. Nanotechnology in cancer drug delivery and selective targeting.Int. Sch. Res. Not.2014201411210.1155/2014/939378
    [Google Scholar]
  154. FicaiD. FicaiA. New challenges in cancer treatment, from novel agents to innovative administration.Anticancer. Agents Med. Chem.20191914510.2174/18715206190119032111483531204621
    [Google Scholar]
  155. Ram PrasadR.P. Rishikesh PandeyR.P. Ajit VarmaA.V. Ishan BarmanI.B. Polymer-based nanoparticles for drug delivery systems and cancer therapeutics.Natural polymers for drug delivery.CABI WallingfordUK2017537010.1079/9781780644479.0053
    [Google Scholar]
  156. Sezgin-BayindirZ. Losada-BarreiroS. Bravo-DíazC. SovaM. KristlJ. SasoL. Nanotechnology-based drug delivery to improve the therapeutic benefits of NRF2 modulators in cancer therapy.Antioxidants202110568510.3390/antiox1005068533925605
    [Google Scholar]
  157. PatraJ.K. DasG. FracetoL.F. CamposE.V.R. Rodriguez-TorresM.P. Acosta-TorresL.S. Diaz-TorresL.A. GrilloR. SwamyM.K. SharmaS. HabtemariamS. ShinH.S. Nano based drug delivery systems: Recent developments and future prospects.J. Nanobiotechnology20181617110.1186/s12951‑018‑0392‑830231877
    [Google Scholar]
  158. KumarA. ZhangX. LiangX.J. Gold nanoparticles: Emerging paradigm for targeted drug delivery system.Biotechnol. Adv.201331559360610.1016/j.biotechadv.2012.10.00223111203
    [Google Scholar]
  159. GenchiG. LauriaG. CatalanoA. SinicropiM.S. CarocciA. Biological activity of selenium and its impact on human health.Int. J. Mol. Sci.2023243263310.3390/ijms2403263336768955
    [Google Scholar]
  160. El-FakharanyE.M. Abu-SerieM.M. IbrahimA. EltarahonyM. Anticancer activity of lactoferrin-coated biosynthesized selenium nanoparticles for combating different human cancer cells via mediating apoptotic effects.Sci. Rep.2023131957910.1038/s41598‑023‑36492‑837311791
    [Google Scholar]
  161. SunT. GaoJ. HanD. ShiH. LiuX. Fabrication and characterization of solid lipid nano-formulation of astraxanthin against DMBA-induced breast cancer via Nrf-2-Keap1 and NF-kB and mTOR/Maf-1/PTEN pathway.Drug Deliv.201926197598810.1080/10717544.2019.166745431556759
    [Google Scholar]
  162. JiangM. JinJ. YeX. WangJ. ShenH. ZhenJ. ZhouY. Construction of lycetin nanocarriers and its effect on the proliferation and apoptosis of hepatocellular carcinoma cells by regulating nuclear factor E2 related factor/antioxidant response element pathway.J. Nanosci. Nanotechnol.20212121054106010.1166/jnn.2021.1863033183443
    [Google Scholar]
  163. LiJ. ChengX. ChenY. HeW. NiL. XiongP. WeiM. Vitamin E TPGS modified liposomes enhance cellular uptake and targeted delivery of luteolin: An in vivo/in vitro evaluation.Int. J. Pharm.2016512126227210.1016/j.ijpharm.2016.08.03727545748
    [Google Scholar]
  164. YangA. SunZ. LiuR. LiuX. ZhangY. ZhouY. QiuY. ZhangX. Transferrin-conjugated erianin-loaded liposomes suppress the growth of liver cancer by modulating oxidative stress.Front. Oncol.20211172760510.3389/fonc.2021.72760534513705
    [Google Scholar]
  165. ZhaoY. XiaoW. PengW. HuangQ. WuK. EvansC.E. LiuX. JinH. Oridonin-loaded nanoparticles inhibit breast cancer progression through regulation of ROS-related Nrf2 signaling pathway.Front. Bioeng. Biotechnol.2021960057910.3389/fbioe.2021.60057933898397
    [Google Scholar]
  166. SathiyaseelanA. SaravanakumarK. JayalakshmiJ. GopiM. ShajahanA. BarathikannanK. KalaichelvanP.T. WangM.H. Trigonelline-loaded chitosan nanoparticles prompted antitumor activity on glioma cells and biocompatibility with pheochromocytoma cells.Int. J. Biol. Macromol.2020163364310.1016/j.ijbiomac.2020.06.16532585274
    [Google Scholar]
  167. JeongY.I.L. KimD.H. ChungK.D. KimY.H. LeeY.S. ChoiK.C. Antitumor activity of trigonelline-incorporated chitosan nanoparticles.J. Nanosci. Nanotechnol.20141485633563710.1166/jnn.2014.881825935980
    [Google Scholar]
  168. GaiC. LiuC. WuX. YuM. ZhengJ. ZhangW. LvS. LiW. MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells.Cell Death Dis.202011975110.1038/s41419‑020‑02939‑332929075
    [Google Scholar]
  169. Raj RK. DE. SR. β-Sitosterol-assisted silver nanoparticles activates Nrf2 and triggers mitochondrial apoptosis via oxidative stress in human hepatocellular cancer cell line.J. Biomed. Mater. Res. A202010891899190810.1002/jbm.a.3695332319188
    [Google Scholar]
  170. HsiehC.H. HsiehH.C. ShihF.H. WangP.W. YangL.X. ShiehD.B. WangY.C. An innovative NRF2 nano- modulator induces lung cancer ferroptosis and elicits an immunostimulatory tumor microenvironment.Theranostics202111147072709110.7150/thno.5780334093872
    [Google Scholar]
  171. SunH. CaiH. XuC. ZhaiH. LuxF. XieY. FengL. DuL. LiuY. SunX. WangQ. SongH. HeN. ZhangM. JiK. WangJ. GuY. LeducG. DoussineauT. WangY. LiuQ. TillementO. AGuIX nanoparticles enhance ionizing radiation-induced ferroptosis on tumor cells by targeting the NRF2-GPX4 signaling pathway.J. Nanobiotechnology202220144910.1186/s12951‑022‑01654‑936242003
    [Google Scholar]
  172. LanQ. WangS. ChenZ. HuaJ. HuJ. LuoS. XuY. Near-infrared-responsive GE11-CuS@Gal nanoparticles as an intelligent drug release system for targeting therapy against oral squamous cell carcinoma.Int. J. Pharm.202464912366710.1016/j.ijpharm.2023.12366738048890
    [Google Scholar]
  173. SalantiA. ClausenT.M. AgerbækM.Ø. Al NakouziN. DahlbäckM. OoH.Z. LeeS. GustavssonT. RichJ.R. HedbergB.J. MaoY. BaringtonL. PereiraM.A. LoBelloJ. EndoM. FazliL. SodenJ. WangC.K. SanderA.F. DagilR. ThraneS. HolstP.J. MengL. FaveroF. WeissG.J. NielsenM.A. FreethJ. NielsenT.O. ZaiaJ. TranN.L. TrentJ. BabcookJ.S. TheanderT.G. SorensenP.H. DaugaardM. Targeting human cancer by a glycosaminoglycan binding malaria protein.Cancer Cell201528450051410.1016/j.ccell.2015.09.00326461094
    [Google Scholar]
  174. ChenX. YinT. ZhangB. SunB. ChenJ. XiaoT. WangB. LiM. YangJ. FanX. Inhibitory effects of brusatol delivered using glycosaminoglycan-placental chondroitin sulfate A -modified nanoparticles on the proliferation, migration and invasion of cancer cells.Int. J. Mol. Med.202046281782710.3892/ijmm.2020.462732626948
    [Google Scholar]
  175. TrivediM. SinghA. TalekarM. PawarG. ShahP. AmijiM. MicroRNA-34a encapsulated in hyaluronic acid nanoparticles induces epigenetic changes with altered mitochondrial bioenergetics and apoptosis in non-small-cell lung cancer cells.Sci. Rep.201771363610.1038/s41598‑017‑02816‑828623259
    [Google Scholar]
  176. VelavanB. DivyaT. SureshkumarA. SudhandiranG. Nano-chemotherapeutic efficacy of (−) -epigallocatechin 3-gallate mediating apoptosis in A549 cells: Involvement of reactive oxygen species mediated Nrf2/Keap1signaling.Biochem. Biophys. Res. Commun.201850331723173110.1016/j.bbrc.2018.07.10530075845
    [Google Scholar]
  177. SajadimajdS. AghazF. KhazaeiM. RayganiA.V. The anti-cancer effect of resveratrol nano-encapsulated supplements against breast cancer via the regulation of oxidative stress.J. Microencapsul.202340531832910.1080/02652048.2023.219802637017511
    [Google Scholar]
  178. SabzichiM. MohammadianJ. BazzazR. PirouzpanahM.B. ShaakerM. HamishehkarH. ChavoshiH. SalehiR. SamadiN. Chrysin loaded nanostructured lipid carriers (NLCs) triggers apoptosis in MCF-7 cancer cells by inhibiting the Nrf2 pathway.Process Biochem.201760849110.1016/j.procbio.2017.05.024
    [Google Scholar]
  179. Farkhondeh, T.; Samarghandian, S.; Azimin-Nezhad, M.; Samini, F. Effect of chrysin on nociception in formalin test and serum levels of noradrenalin and corticosterone in rats. Int. J. Clin. Exper. Med.. 2015, 8(2), 2465.10.3389/fphar.2022.108966736686682
  180. SkrzypekK. TertilM. GoldaS. CieslaM. WeglarczykK. ColletG. GuichardA. KozakowskaM. BoczkowskiJ. WasH. GilT. KuzdzalJ. MuchovaL. VitekL. LobodaA. JozkowiczA. KiedaC. DulakJ. Interplay between heme oxygenase-1 and miR-378 affects non-small cell lung carcinoma growth, vascularization, and metastasis.Antioxid. Redox Signal.201319764466010.1089/ars.2013.518423617628
    [Google Scholar]
  181. JeanC. ChenX.L. NamJ.O. TancioniI. UryuS. LawsonC. WardK.K. WalshC.T. MillerN.L.G. GhassemianM. TurowskiP. DejanaE. WeisS. ChereshD.A. SchlaepferD.D. Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function.J. Cell Biol.2014204224726310.1083/jcb.20130706724446483
    [Google Scholar]
  182. ChenW. LiZ. YuN. ZhangL. LiH. ChenY. GongF. LinW. HeX. WangS. WuY. JiG. Bone- targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells.J. Nanobiotechnology202321135510.1186/s12951‑023‑02129‑137775799
    [Google Scholar]
  183. LiuP.L. TsaiJ.R. CharlesA.L. HwangJ.J. ChouS.H. PingY.H. LinF.Y. ChenY.L. HungC.Y. ChenW.C. ChenY.H. ChongI.W. Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases.Mol. Nutr. Food Res.201054S2S196S20410.1002/mnfr.20090055020461740
    [Google Scholar]
  184. Abu-SerieM.M. EltarahonyM. Novel nanoformulation of disulfiram with bacterially synthesized copper oxide nanoparticles for augmenting anticancer activity: An in vitro study.Cancer Nanotechnol.20211212510.1186/s12645‑021‑00097‑533456622
    [Google Scholar]
  185. AmbrosioL. ArgenzianoM. CucciM.A. GrattarolaM. de GraafI.A.M. DianzaniC. BarreraG. Sánchez NievesJ. GomezR. CavalliR. PizzimentiS. Carbosilane dendrimers loaded with siRNA targeting Nrf2 as a tool to overcome cisplatin chemoresistance in bladder cancer cells.Antioxidants202091099310.3390/antiox910099333066634
    [Google Scholar]
  186. SabzichiM. HamishehkarH. RamezaniF. SharifiS. TabasinezhadM. PirouzpanahM. GhanbariP. SamadiN. Luteolin-loaded phytosomes sensitize human breast carcinoma MDA-MB 231 cells to doxorubicin by suppressing Nrf2 mediated signalling.Asian Pac. J. Cancer Prev.201415135311531610.7314/APJCP.2014.15.13.531125040994
    [Google Scholar]
  187. PanieriE. SasoL. Potential applications of NRF2 inhibitors in cancer therapy.Oxid. Med. Cell Longev.20192019859234810.1155/2019/859234831097977
    [Google Scholar]
  188. SovaM. SasoL. Design and development of Nrf2 modulators for cancer chemoprevention and therapy: A review.Drug Des. Devel. Ther.2018123181319710.2147/DDDT.S17261230288023
    [Google Scholar]
  189. AhmadianS. SabzichiM. RashidiM. MohammadianJ. MahmoudiS. MaroufiN.F. RamezaniF. GhorbaniM. MohammadiM. PirouzpanahM. BijanpourH. Sensitization of A-549 lung cancer cells to Cisplatin by Quinacrine-loaded lipidic nanoparticles via suppressing Nrf2 mediated defense mechanism.Naunyn Schmiedebergs Arch. Pharmacol.202139471521152810.1007/s00210‑021‑02079‑133735393
    [Google Scholar]
  190. KuS.H. JoS.D. LeeY.K. KimK. KimS.H. Chemical and structural modifications of RNAi therapeutics.Adv. Drug Deliv. Rev.2016104162810.1016/j.addr.2015.10.01526549145
    [Google Scholar]
  191. CavalliR. PrimoL. SessaR. ChiaverinaG. di BlasioL. AlongiJ. ManfrediA. RanucciE. FerrutiP. The AGMA1 polyamidoamine mediates the efficient delivery of siRNA.J. Drug Target.2017259-1089189810.1080/1061186X.2017.136321528817973
    [Google Scholar]
  192. KhodakaramiA. KashaniM.A. NazerA. KheshtiA.M. RashidiB. KarpishehV. MasjediA. AbolhasaniS. IzadiS. BagherifarR. HejazianS.S. MohammadiH. MovassaghpourA. FeiziA.A.H. Hojjat-FarsangiM. Jadidi-NiaraghF. Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide.Cell Commun. Signal.202321118810.1186/s12964‑023‑01213‑137528446
    [Google Scholar]
  193. LiuW. HuT. ZhouL. WuD. HuangX. RenX. LvY. HongW. HuangG. LinZ. LiuJ. Nrf2 protects against oxidative stress induced by SiO2 nanoparticles.Nanomedicine (Lond.)201712192303231810.2217/nnm‑2017‑004628952419
    [Google Scholar]
  194. Pirpour TazehkandA. SalehiR. VelaeiK. SamadiN. The potential impact of trigonelline loaded micelles on Nrf2 suppression to overcome oxaliplatin resistance in colon cancer cells.Mol. Biol. Rep.20204785817582910.1007/s11033‑020‑05650‑w32661875
    [Google Scholar]
  195. MahmoudA.M. DesoukyE.M. HozayenW.G. Bin-JumahM. El-NahassE.S. SolimanH.A. FarghaliA.A. Mesoporous silica nanoparticles trigger liver and kidney injury and fibrosis via altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 signaling in rats.Biomolecules201991052810.3390/biom910052831557909
    [Google Scholar]
  196. Bashandy PhDM.M. SaeedH.E. AhmedW.M.S. IbrahimM.A. ShehataO. Cerium oxide nanoparticles attenuate the renal injury induced by cadmium chloride via improvement of the NBN and Nrf2 gene expressions in rats.Toxicol. Res. (Camb.)202211233934710.1093/toxres/tfac00935510236
    [Google Scholar]
  197. MahmoudiS. GhorbaniM. SabzichiM. RamezaniF. HamishehkarH. SamadiN. Targeted hyaluronic acid-based lipid nanoparticle for apigenin delivery to induce Nrf2-dependent apoptosis in lung cancer cells.J. Drug Deliv. Sci. Technol.20194926827610.1016/j.jddst.2018.11.013
    [Google Scholar]
  198. ChenG. ChangW. LiX. HanL. ZhouD. FengY. LiB. ZhuF. LiN. n-BuOH extract of Bletilla striata exerts chemopreventive effects on lung against SiO2 nanoparticles through activation of Nrf2 pathway.Phytomedicine20218215344510.1016/j.phymed.2020.15344533418138
    [Google Scholar]
  199. RasoolM. MalikA. WaquarS. AroojM. ZahidS. AsifM. ShaheenS. HussainA. UllahH. GanS.H. New challenges in the use of nanomedicine in cancer therapy.Bioengineered202213175977310.1080/21655979.2021.201290734856849
    [Google Scholar]
  200. JiangJ. OberdörsterG. BiswasP. Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies.J. Nanopart. Res.2009111778910.1007/s11051‑008‑9446‑4
    [Google Scholar]
  201. AwasthiR. PantI. T KulkarniG. Satiko KikuchiI. de Jesus Andreoli PintoT. DuaK. Ramana MalipeddiV. Opportunities and challenges in nano-structure mediated drug delivery: Where do we stand?Curr. Nanomed.2016627810410.2174/2468187306666160808160330
    [Google Scholar]
  202. XiaY. RaoL. YaoH. WangZ. NingP. ChenX. Engineering macrophages for cancer immunotherapy and drug delivery.Adv. Mater.20203240200205410.1002/adma.20200205432856350
    [Google Scholar]
  203. DobrovolskaiaM.A. AggarwalP. HallJ.B. McNeilS.E. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution.Mol. Pharm.20085448749510.1021/mp800032f18510338
    [Google Scholar]
  204. Ashrafizadeh, M.; Fekri, HS.; Ahmadi, Z.; Farkhondeh, T.; Samarghandian, S. Therapeutic and biological activities of berberine: The involvement of Nrf2 signaling pathway. J. Cell. Biochem., 2020, 121(2), 1575-85.10.1038/nbt140218438401
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