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Volume 21, Issue 4
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

A malignant tumor is a frequent and common disease that severely threatens human health. Many mechanisms, such as cell signaling pathway, anti-apoptosis mechanism, cell stemness, metabolism, and cell phenotype, have been studied to explain the reasons for chemotherapy, radioresistance, and tumor recurrences in antitumor treatment. Cancer stem cells (CSCs) are important tumor cell subclasses that can potentially organize and regulate stem cell properties. Growing evidence suggests that CSCs can initiate tumors and constitute a significant factor in metastasis, recurrence, and treatment resistance. The inability to completely target and remove CSCs is a considerable obstacle in tumor treatment. Therefore, drugs and therapeutic strategies that can effectively intervene with CSCs are essential for the treatment of different tumor types. However, the current strategies and efficacy of targeted elimination of CSCs are very limited. Oxidative stress has been recognized to play a crucial role in cancer pathophysiology. Moreover, reactive oxygen species (ROS) production and imbalance of the built-in cellular antioxidant defense system are hallmarks of tumor and cancer etiology. The current paper will focus on the regulation and mechanism behind oxidative stress in tumors and cancer stem cells and its tumor therapy applications. Additionally, the article discusses the role of CSCs in causing tumor treatment resistance and recurrence based on a redox perspective. The study also emphasizes that targeted modulation of oxidative stress in CSCs has great potential in tumor therapy, providing novel prospects for tumor therapy.

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2025-06-18

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References

  1. CaoW. ChenH.D. YuY.W. LiN. ChenW.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020.Chin. Med. J.2021134778379110.1097/CM9.000000000000147433734139
     [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. LiZ. FeiyueZ. GaofengL. Traditional Chinese medicine and lung cancer——From theory to practice.Biomed. Pharmacother.202113711138110.1016/j.biopha.2021.11138133601147
     [Google Scholar]
  4. ZhangX. QiuH. LiC. CaiP. QiF. The positive role of traditional Chinese medicine as an adjunctive therapy for cancer.Biosci. Trends202115528329810.5582/bst.2021.0131834421064
     [Google Scholar]
  5. ZhangY. LouY. WangJ. YuC. ShenW. Research status and molecular mechanism of the traditional chinese medicine and antitumor therapy combined strategy based on tumor microenvironment.Front. Immunol.20211160970510.3389/fimmu.2020.60970533552068
     [Google Scholar]
  6. OtaN. YoshimotoY. DarwisN.D.M. SatoH. AndoK. OikeT. OhnoT. High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy.Jpn. J. Radiol.202240553454110.1007/s11604‑021‑01230‑534860358
     [Google Scholar]
  7. ArnethB. Tumor microenvironment.Medicina20195611510.3390/medicina5601001531906017
     [Google Scholar]
  8. EckerdtF.D. BellJ.B. GonzalezC. OhM.S. PerezR.E. MazewskiC. FischiettiM. GoldmanS. NakanoI. PlataniasL.C. Combined PI3Kα-mTOR targeting of glioma stem cells.Sci. Rep.20201012187310.1038/s41598‑020‑78788‑z33318517
     [Google Scholar]
  9. LendeckelU. WolkeC. Redox-regulation in cancer stem cells.Biomedicines20221010241310.3390/biomedicines1010241336289675
     [Google Scholar]
  10. NajafiM. FarhoodB. MortezaeeK. Cancer stem cells (CSCs) in cancer progression and therapy.J. Cell. Physiol.201923468381839510.1002/jcp.2774030417375
     [Google Scholar]
  11. WangY.Y. WangW.D. SunZ.J. Cancer stem cell‐immune cell collusion in immunotherapy.Int. J. Cancer2023153469470810.1002/ijc.3442136602290
     [Google Scholar]
  12. BayikD. LathiaJ.D. Cancer stem cell–immune cell crosstalk in tumour progression.Nat. Rev. Cancer202121852653610.1038/s41568‑021‑00366‑w34103704
     [Google Scholar]
  13. XiaoY. YuD. Tumor microenvironment as a therapeutic target in cancer.Pharmacol. Ther.202122110775310.1016/j.pharmthera.2020.10775333259885
     [Google Scholar]
  14. ChinnS.B. DarrO.A. OwenJ.H. BellileE. McHughJ.B. SpectorM.E. PapagerakisS.M. ChepehaD.B. BradfordC.R. CareyT.E. PrinceM.E.P. Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma.Head Neck201537331732610.1002/hed.2360024415402
     [Google Scholar]
  15. WangS. MaS. LiX. XueZ. ZhangX. FanW. NieY. WuK. ChenX. CaoF. Attenuation of lung cancer stem cell tumorigenesis and metastasis by cisplatin.Exp. Lung Res.201440840441410.3109/01902148.2014.93820125153512
     [Google Scholar]
  16. WiwanitkitV. Oxidative stress and metabolic syndrome.Korean J. Fam. Med.20143514410.4082/kjfm.2014.35.1.4424501670
     [Google Scholar]
  17. WatsonJ.D. Type 2 diabetes as a redox disease.Lancet2014383991984184310.1016/S0140‑6736(13)62365‑X24581668
     [Google Scholar]
  18. PrakashR. FauziaE. SiddiquiA.J. YadavS.K. KumariN. ShamsM.T. NaeemA. PraharajP.P. KhanM.A. BhutiaS.K. JanowskiM. BoltzeJ. RazaS.S. Oxidative stress-induced autophagy compromises stem cell viability.Stem Cells202240546847810.1093/stmcls/sxac01835294968
     [Google Scholar]
  19. ReczekC.R. ChandelN.S. ROS promotes cancer cell survival through calcium signaling.Cancer Cell201833694995110.1016/j.ccell.2018.05.01029894695
     [Google Scholar]
  20. GorriniC. HarrisI.S. MakT.W. Modulation of oxidative stress as an anticancer strategy.Nat. Rev. Drug Discov.2013121293194710.1038/nrd400224287781
     [Google Scholar]
  21. WielC. Le GalK. IbrahimM.X. JahangirC.A. KashifM. YaoH. ZieglerD.V. XuX. GhoshT. MondalT. KanduriC. LindahlP. SayinV.I. BergoM.O. BACH1 stabilization by antioxidants stimulates lung cancer metastasis.Cell20191782330345.e2210.1016/j.cell.2019.06.00531257027
     [Google Scholar]
  22. WangW. SunH. CheY. JiangX. Rasfonin promotes autophagy and apoptosis via upregulation of reactive oxygen species (ROS)/JNK pathway.Mycology201672647310.1080/21501203.2016.117007330123617
     [Google Scholar]
  23. BhuyanS. PalB. PathakL. SaikiaP.J. MitraS. GayanS. MokhtariR.B. LiH. RamanaC.V. BaishyaD. DasB. Targeting hypoxia-induced tumor stemness by activating pathogen-induced stem cell niche defense.Front. Immunol.20221393332910.3389/fimmu.2022.93332936248858
     [Google Scholar]
  24. LapidotT. SirardC. VormoorJ. MurdochB. HoangT. CortesC.J. MindenM. PatersonB. CaligiuriM.A. DickJ.E. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.Nature1994367646464564810.1038/367645a07509044
     [Google Scholar]
  25. Al-HajjM. WichaM.S. HernandezB.A. MorrisonS.J. ClarkeM.F. Prospective identification of tumorigenic breast cancer cells.Proc. Natl. Acad. Sci.200310073983398810.1073/pnas.053029110012629218
     [Google Scholar]
  26. MeuwissenK.P.V. GuJ.W. ZhangT.C. JoostenE.A.J. Conventional-SCS vs. burst-SCS and the behavioral effect on mechanical hypersensitivity in a rat model of chronic neuropathic pain: Effect of amplitude.Neuromodulation2018211193010.1111/ner.1273129178358
     [Google Scholar]
  27. GaoW. XuS. ZhangM. LiuS. SiuS.P. PengH. NgJ.C. TsaoG.S. ChanA.W. ChowV.L. ChanJ.Y. WongT.S. NADPH oxidase 5α promotes the formation of CD271 tumor-initiating cells in oral cancer.Am. J. Cancer Res.20201061710172732642285
     [Google Scholar]
  28. AlvinaF.B. GouwA.M. LeA. Cancer stem cell metabolism.Adv. Exp. Med. Biol.2021131116117210.1007/978‑3‑030‑65768‑0_1234014542
     [Google Scholar]
  29. TuY. ZhouY. ZhangD. YangJ. LiX. JiK. WuX. LiuR. ZhangQ. Light-induced reactive oxygen species (ROS) generator for tumor therapy through an ROS burst in mitochondria and AKT-inactivation-induced apoptosis.ACS Appl. Bio Mater.2021465222523010.1021/acsabm.1c0038635007004
     [Google Scholar]
  30. Čipak GašparovićA. MilkovićL. DandachiN. StanzerS. PezdircI. VrančićJ. ŠitićS. SuppanC. BalicM. Chronic oxidative stress promotes molecular changes associated with epithelial mesenchymal transition, NRF2, and breast cancer stem cell phenotype.Antioxidants201981263310.3390/antiox812063331835715
     [Google Scholar]
  31. van der PostS. BirchenoughG.M.H. HeldJ.M. NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation.Cell Rep.202135110894910.1016/j.celrep.2021.10894933826887
     [Google Scholar]
  32. ChenK. PanF. JiangH. ChenJ. PeiL. XieF. LiangH. Highly enriched CD133+CD44+ stem-like cells with CD133+CD44high metastatic subset in HCT116 colon cancer cells.Clin. Exp. Metastasis201128875176310.1007/s10585‑011‑9407‑721750907
     [Google Scholar]
  33. HeA. YangX. HuangY. FengT. WangY. SunY. ShenZ. YaoY. CD133 + CD44 + cells mediate in the lung metastasis of osteosarcoma.J. Cell. Biochem.201511681719172910.1002/jcb.2513125736420
     [Google Scholar]
  34. LiangW. LuoQ. ZhangZ. YangK. YangA. ChiQ. HuH. An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1, pathways and immune infiltration in diabetic nephropathy mice.Biocell20224681989200210.32604/biocell.2022.019300
     [Google Scholar]
  35. XuR. WuQ. GongY. WuY. ChiQ. SunD. A novel prognostic target-gene signature and nomogram based on an integrated bioinformatics analysis in hepatocellular carcinoma.Biocell20224651261128810.32604/biocell.2022.018427
     [Google Scholar]
  36. FangM. GuoJ. WangH. YangZ. ZhaoH. ChiQ. WGCNA and LASSO algorithm constructed an immune infiltration-related 5-gene signature and nomogram to improve prognosis prediction of hepatocellular carcinoma.Biocell202246240141510.32604/biocell.2022.016989
     [Google Scholar]
  37. TianF. HuH. WangD. DingH. ChiQ. LiangH. ZengW. Immune-related DNA methylation signature associated with APLN expression predicts prognostic of hepatocellular carcinoma.Biocell202246102291230110.32604/biocell.2022.020198
     [Google Scholar]
  38. LvS. AnY. DongH. XieL. ZhengH. ChengX. ZhangL. TengT. WangQ. YanZ. GuoX. High APLN expression predicts poor prognosis for glioma patients.Oxid. Med. Cell. Longev.2022202211610.1155/2022/839333636193059
     [Google Scholar]
  39. HuangR. RofstadE.K. Cancer stem cells (CSCs), cervical CSCs and targeted therapies.Oncotarget2017821353513536710.18632/oncotarget.1016927343550
     [Google Scholar]
  40. ZhangJ. WangX. VikashV. YeQ. WuD. LiuY. DongW. ROS and ROS-mediated cellular signaling.Oxid. Med. Cell. Longev.2016201611810.1155/2016/435096526998193
     [Google Scholar]
  41. ZorovD.B. JuhaszovaM. SollottS.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release.Physiol. Rev.201494390995010.1152/physrev.00026.201324987008
     [Google Scholar]
  42. YuL. LuM. JiaD. MaJ. Ben-JacobE. LevineH. KaipparettuB.A. OnuchicJ.N. Modeling the genetic regulation of cancer metabolism: Interplay between glycolysis and oxidative phosphorylation.Cancer Res.20177771564157410.1158/0008‑5472.CAN‑16‑207428202516
     [Google Scholar]
  43. PolireddyK. DongR. ReedG. YuJ. ChenP. WilliamsonS. VioletP.C. PessettoZ. GodwinA.K. FanF. LevineM. DriskoJ.A. ChenQ. High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: Mechanisms and a phase I/IIa study.Sci. Rep.2017711718810.1038/s41598‑017‑17568‑829215048
     [Google Scholar]
  44. SuX. ShenZ. YangQ. SuiF. PuJ. MaJ. MaS. YaoD. JiM. HouP. Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms.Theranostics20199154461447310.7150/thno.3521931285773
     [Google Scholar]
  45. TangX.H. GudasL.J. Retinoids, retinoic acid receptors, and cancer.Annu. Rev. Pathol.20116134536410.1146/annurev‑pathol‑011110‑13030321073338
     [Google Scholar]
  46. L SuraweeraT. RupasingheH.P.V. DellaireG. XuZ. Regulation of Nrf2/ARE pathway by dietary flavonoids: A friend or foe for cancer management?Antioxidants202091097310.3390/antiox910097333050575
     [Google Scholar]
  47. MetcalfeN.B. OlssonM. How telomere dynamics are influenced by the balance between mitochondrial efficiency, reactive oxygen species production and DNA damage.Mol. Ecol.202231236040605234435398
     [Google Scholar]
  48. CastelliS. CiccaroneF. De FalcoP. CirioloM.R. Adaptive antioxidant response to mitochondrial fatty acid oxidation determines the proliferative outcome of cancer cells.Cancer Lett.202355421601010.1016/j.canlet.2022.21601036402229
     [Google Scholar]
  49. ZhengY.L. TuZ.S. CuiH.M. YanS. DuanD.C. TangW. DaiF. ZhouB. Redox-based strategy for selectively inducing energy crisis inside cancer cells: An example of modifying dietary curcumin to target mitochondria.J. Agric. Food Chem.20227092898291010.1021/acs.jafc.1c0769035213152
     [Google Scholar]
  50. ChoromańskaB. MyśliwiecP. KozłowskiT. ŁukaszewiczJ. VasilyevichH.P. DadanJ. ZalewskaA. MaciejczykM. Antioxidant and antiradical activities depend on adrenal tumor type.Front. Endocrinol.202213101104310.3389/fendo.2022.101104336246875
     [Google Scholar]
  51. PatilT. RohiwalS.S. TiwariA.P. Stem cells: Therapeutic implications in chemotherapy and radiotherapy resistance in cancer therapy.Curr. Stem Cell Res. Ther.202318675076510.2174/1574888X1766622100312520836200212
     [Google Scholar]
  52. RamosA. dos SantosM.M. de MacedoG.T. WildnerG. PrestesA.S. MasudaC.A. CorteD.C.L. da RochaT.J.B. BarbosaN.V. Methyl and ethylmercury elicit oxidative stress and unbalance the antioxidant system in saccharomyces cerevisiae.Chem. Biol. Interact.202031510886710.1016/j.cbi.2019.10886731672467
     [Google Scholar]
  53. FengJ. ZhaoD. LvF. YuanZ. Epigenetic inheritance from normal origin cells can determine the aggressive biology of tumor-initiating cells and tumor heterogeneity.Cancer Contr.20222910.1177/1073274822107816035213254
     [Google Scholar]
  54. GalluzziL. VitaleI. AaronsonS.A. AbramsJ.M. AdamD. AgostinisP. AlnemriE.S. AltucciL. AmelioI. AndrewsD.W. PetruzzelliA.M. AntonovA.V. AramaE. BaehreckeE.H. BarlevN.A. BazanN.G. BernassolaF. BertrandM.J.M. BianchiK. BlagosklonnyM.V. BlomgrenK. BornerC. BoyaP. BrennerC. CampanellaM. CandiE. GutierrezC.D. CecconiF. ChanF.K.M. ChandelN.S. ChengE.H. ChipukJ.E. CidlowskiJ.A. CiechanoverA. CohenG.M. ConradM. RuizC.J.R. CzabotarP.E. D’AngiolellaV. DawsonT.M. DawsonV.L. De LaurenziV. De MariaR. DebatinK.M. DeBerardinisR.J. DeshmukhM. DanieleD.N. VirgilioD.F. DixitV.M. DixonS.J. DuckettC.S. DynlachtB.D. El-DeiryW.S. ElrodJ.W. FimiaG.M. FuldaS. SáezG.A.J. GargA.D. GarridoC. GavathiotisE. GolsteinP. GottliebE. GreenD.R. GreeneL.A. GronemeyerH. GrossA. HajnoczkyG. HardwickJ.M. HarrisI.S. HengartnerM.O. HetzC. IchijoH. JäätteläM. JosephB. JostP.J. JuinP.P. KaiserW.J. KarinM. KaufmannT. KeppO. KimchiA. KitsisR.N. KlionskyD.J. KnightR.A. KumarS. LeeS.W. LemastersJ.J. LevineB. LinkermannA. LiptonS.A. LockshinR.A. López-OtínC. LoweS.W. LueddeT. LugliE. MacFarlaneM. MadeoF. MalewiczM. MalorniW. ManicG. MarineJ.C. MartinS.J. MartinouJ.C. MedemaJ.P. MehlenP. MeierP. MelinoS. MiaoE.A. MolkentinJ.D. MollU.M. Muñoz-PinedoC. NagataS. NuñezG. OberstA. OrenM. OverholtzerM. PaganoM. PanaretakisT. PasparakisM. PenningerJ.M. PereiraD.M. PervaizS. PeterM.E. PiacentiniM. PintonP. PrehnJ.H.M. PuthalakathH. RabinovichG.A. RehmM. RizzutoR. RodriguesC.M.P. RubinszteinD.C. RudelT. RyanK.M. SayanE. ScorranoL. ShaoF. ShiY. SilkeJ. SimonH.U. SistiguA. StockwellB.R. StrasserA. SzabadkaiG. TaitS.W.G. TangD. TavernarakisN. ThorburnA. TsujimotoY. TurkB. BergheV.T. VandenabeeleP. HeidenV.M.G. VillungerA. VirginH.W. VousdenK.H. VucicD. WagnerE.F. WalczakH. WallachD. WangY. WellsJ.A. WoodW. YuanJ. ZakeriZ. ZhivotovskyB. ZitvogelL. MelinoG. KroemerG. Molecular mechanisms of cell death: Recommendations of the nomenclature committee on cell death 2018.Cell Death Differ.201825348654110.1038/s41418‑017‑0012‑429362479
     [Google Scholar]
  55. ChenY. OharaT. XingB. QiJ. NomaK. MatsukawaA. A promising new anti-cancer strategy: Iron chelators targeting CSCs.Acta Med. Okayama20207411632099242
     [Google Scholar]
  56. JiangY. HuoZ. QiX. ZuoT. WuZ. Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes.Nanomedicine202217530332410.2217/nnm‑2021‑037435060391
     [Google Scholar]
  57. JeongS.D. JungB.K. LeeD. HaJ. ChangH.G. LeeJ. LeeS. YunC.O. KimY.C. Enhanced immunogenic cell death by apoptosis/ferroptosis hybrid pathway potentiates pd-l1 blockade cancer immunotherapy.ACS Biomater. Sci. Eng.20228125188519810.1021/acsbiomaterials.2c0095036449494
     [Google Scholar]
  58. HuangS. ChenY. HuY. ShiY. XiaoQ. LiZ. KangJ. ZhouQ. ShenG. JiaH. Downregulation of MCF2L promoted the ferroptosis of hepatocellular carcinoma cells through PI3K/mTOR pathway in a RhoA/Rac1 dependent manner.Dis. Markers2022202211310.1155/2022/613894136330204
     [Google Scholar]
  59. LiX. ZengJ. LiuY. LiangM. LiuQ. LiZ. ZhaoX. ChenD. Inhibitory effect and mechanism of action of quercetin and quercetin diels-alder anti-dimer on erastin-induced ferroptosis in bone marrow-derived mesenchymal stem cells.Antioxidants20209320510.3390/antiox903020532131401
     [Google Scholar]
  60. ZhouD. ShaoL. SpitzD.R. Reactive oxygen species in normal and tumor stem cells.Adv. Cancer Res.201412216710.1016/B978‑0‑12‑420117‑0.00001‑324974178
     [Google Scholar]
  61. WangL. LiuY. DuT. YangH. LeiL. GuoM. DingH.F. ZhangJ. WangH. ChenX. YanC. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc–.Cell Death Differ.202027266267510.1038/s41418‑019‑0380‑z31273299
     [Google Scholar]
  62. LeiG. ZhangY. HongT. ZhangX. LiuX. MaoC. YanY. KoppulaP. ChengW. SoodA.K. LiuJ. GanB. Ferroptosis as a mechanism to mediate p53 function in tumor radiosensitivity.Oncogene202140203533354710.1038/s41388‑021‑01790‑w33927351
     [Google Scholar]
  63. IshimotoT. NaganoO. YaeT. TamadaM. MotoharaT. OshimaH. OshimaM. IkedaT. AsabaR. YagiH. MasukoT. ShimizuT. IshikawaT. KaiK. TakahashiE. ImamuraY. BabaY. OhmuraM. SuematsuM. BabaH. SayaH. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth.Cancer Cell201119338740010.1016/j.ccr.2011.01.03821397861
     [Google Scholar]
  64. BegicevicR.R. ArfusoF. FalascaM. Bioactive lipids in cancer stem cells.World J. Stem Cells201911969370410.4252/wjsc.v11.i9.69331616544
     [Google Scholar]
  65. XuX. ZhangX. WeiC. ZhengD. LuX. YangY. LuoA. ZhangK. DuanX. WangY. Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis.Eur. J. Pharm. Sci.202015210545010.1016/j.ejps.2020.10545032621966
     [Google Scholar]
  66. WuQ. NeedsP.W. LuY. KroonP.A. RenD. YangX. Different antitumor effects of quercetin, quercetin-3′-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells.Food Funct.2018931736174610.1039/C7FO01964E29497723
     [Google Scholar]
  67. DodsonM. AnandhanA. ZhangD.D. MadhavanL. An NRF2 perspective on stem cells and ageing.Front. Aging2021269068610.3389/fragi.2021.69068636213179
     [Google Scholar]
  68. 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]
  69. LiX. HeS. ZhouJ. YuX. LiL. LiuY. LiW. Cr (VI) induces abnormalities in glucose and lipid metabolism through ROS/Nrf2 signaling.Ecotoxicol. Environ. Saf.202121911232010.1016/j.ecoenv.2021.11232033991932
     [Google Scholar]
  70. WuT. HarderB.G. WongP.K. LangJ.E. ZhangD.D. Oxidative stress, mammospheres and Nrf2–new implication for breast cancer therapy?Mol. Carcinog.201554111494150210.1002/mc.2220225154499
     [Google Scholar]
  71. MuriJ. KopfM. The thioredoxin system: Balancing redox responses in immune cells and tumors.Eur. J. Immunol.2023531224994836285367
     [Google Scholar]
  72. HuangY. LiW. SuZ. KongA.N.T. The complexity of the Nrf2 pathway: Beyond the antioxidant response.J. Nutr. Biochem.201526121401141310.1016/j.jnutbio.2015.08.00126419687
     [Google Scholar]
  73. KubatkaP. MazurakovaA. SamecM. KoklesovaL. ZhaiK. AL-IshaqR. KajoK. BiringerK. VybohovaD. BrockmuellerA. PecM. ShakibaeiM. GiordanoF.A. BüsselbergD. GolubnitschajaO. Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression—3PM pathways.EPMA J.202112455958710.1007/s13167‑021‑00257‑y34950252
     [Google Scholar]
  74. KuboE. ChhunchhaB. SinghP. SasakiH. SinghD.P. Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress.Sci. Rep.2017711413010.1038/s41598‑017‑14520‑829074861
     [Google Scholar]
  75. PillaiR. HayashiM. ZavitsanouA.M. PapagiannakopoulosT. NRF2: KEAPing tumors protected.Cancer Discov.202212362564310.1158/2159‑8290.CD‑21‑092235101864
     [Google Scholar]
  76. TsaiK.J. TsaiH.Y. TsaiC.C. ChenT.Y. HsiehT.H. ChenC.L. MbuyisaL. HuangY.B. LinM.W. Luteolin inhibits breast cancer stemness and enhances chemosensitivity through the Nrf2-mediated pathway.Molecules20212621645210.3390/molecules2621645234770867
     [Google Scholar]
  77. SunW. MengJ. WangZ. YuanT. QianH. ChenW. TongJ. XieY. ZhangY. ZhaoJ. BaoN. Proanthocyanidins attenuation of H 2 O 2 -induced oxidative damage in tendon-derived stem cells via upregulating nrf-2 signaling pathway.BioMed Res. Int.201720171810.1155/2017/752910429201913
     [Google Scholar]
  78. XiaP. XuX.Y. PI3K/Akt/mTOR signaling pathway in cancer stem cells: From basic research to clinical application.Am. J. Cancer Res.2015551602160926175931
     [Google Scholar]
  79. AhmedE.S.A. AhmedN.H. MedhatA.M. SaidU.Z. RashedL.A. Abdel GhaffarA.R.B. Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model.Tumour Biol.201941410.1177/101042831984680331018830
     [Google Scholar]
  80. ParkJ. KimS.K. HallisS.P. ChoiB.H. KwakM.K. Role of CD133/NRF2 axis in the development of colon cancer stem cell-like properties.Front. Oncol.20221180830010.3389/fonc.2021.80830035155201
     [Google Scholar]
  81. AlipourF. RiyahiN. AzarS.A. SariS. ZandiZ. BashashD. Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO).Int. J. Biochem. Cell Biol.201911610561510.1016/j.biocel.2019.10561531539632
     [Google Scholar]
  82. OuyangX. ShiX. HuangN. YangY. ZhaoW. GuoW. HuangY. WDR72 enhances the stemness of lung cancer cells by activating the AKT/HIF-1α signaling pathway.J. Oncol.2022202211210.1155/2022/505958836385964
     [Google Scholar]
  83. de WinterT.J.J. NusseR. Running against the Wnt: How Wnt/β-catenin suppresses adipogenesis.Front. Cell Dev. Biol.2021962742910.3389/fcell.2021.62742933634128
     [Google Scholar]
  84. HuangR. ZhangL. JinJ. ZhouY. ZhangH. LvC. LuD. WuY. ZhangH. LiuS. ChenH. LuanX. ZhangW. Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction.Acta Pharm. Sin. B202111113481349210.1016/j.apsb.2021.05.00934900531
     [Google Scholar]
  85. OlmosY. GómezS.F.J. WildB. QuintansG.N. CabezudoS. LamasS. MonsalveM. SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex.Antioxid. Redox Signal.201319131507152110.1089/ars.2012.471323461683
     [Google Scholar]
  86. ZengW. LingF. DangK. ChiQ. SPP1 and the risk score model to improve the survival prediction of patients with hepatocellular carcinoma based on multiple algorithms and back propagation neural networks.Biocell202347358159210.32604/biocell.2023.025957
     [Google Scholar]
  87. WeiJ. MarisettyA. SchrandB. GabrusiewiczK. HashimotoY. OttM. GramiZ. KongL.Y. LingX. CarusoH. ZhouS. WangY.A. FullerG.N. HuseJ. GilboaE. KangN. HuangX. VerhaakR. LiS. HeimbergerA.B. Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target.J. Clin. Invest.2018129113714910.1172/JCI12126630307407
     [Google Scholar]
  88. ToscanoV.A. NickelA.C. LiG. KampM.A. MuhammadS. LeprivierG. FritscheE. BarkerR.A. SabelM. SteigerH.J. ZhangW. HänggiD. KahlertU.D. Rapalink-1 targets glioblastoma stem cells and acts synergistically with tumor treating fields to reduce resistance against temozolomide.Cancers20201212385910.3390/cancers1212385933371210
     [Google Scholar]
  89. ViswanathanV. OpdenakerL. ModaraiS. FieldsJ.Z. GonyeG. BomanB.M. MicroRNA expression profiling of normal and malignant human colonic stem cells identifies miRNA92a as a regulator of the LRIG1 stem cell gene.Int. J. Mol. Sci.2020218280410.3390/ijms2108280432316543
     [Google Scholar]
  90. YuanD. FangY. ChenW. JiangK. ZhuG. WangW. ZhangW. YouG. JiaZ. ZhuJ. ZFP36 inhibits tumor progression of human prostate cancer by targeting CDK6 and oxidative stress.Oxid. Med. Cell. Longev.2022202212410.1155/2022/361154036111167
     [Google Scholar]
  91. KrishnaG. PillaiV.S. GopiP. Epstein-Barr virus infection controls the concentration of the intracellular antioxidant glutathione by upregulation of the glutamate transporter EAAT3 in tumor cells.Virus Genes2023591556636344769
     [Google Scholar]
  92. SunQ. GuiZ. ZhaoZ. XuW. ZhuJ. GaoC. ZhaoW. HuH. Overexpression of LncRNA MNX1-AS1/PPFIA4 Activates AKT/HIF-1α Signal Pathway to Promote Stemness of Colorectal Adenocarcinoma Cells.J. Oncol.2022202211610.1155/2022/830340936226248
     [Google Scholar]
  93. LuoM. ShangL. BrooksM.D. JiaggeE. ZhuY. BuschhausJ.M. ConleyS. FathM.A. DavisA. GheordunescuE. WangY. HarouakaR. LozierA. TrinerD. McDermottS. MerajverS.D. LukerG.D. SpitzD.R. WichaM.S. Targeting breast cancer stem cell state equilibrium through modulation of redox signaling.Cell Metab.20182816986.e610.1016/j.cmet.2018.06.00629972798
     [Google Scholar]
  94. DangH. HarryvanT.J. HawinkelsL.J.A.C. Fibroblast subsets in intestinal homeostasis, carcinogenesis, tumor progression, and metastasis.Cancers202113218310.3390/cancers1302018333430285
     [Google Scholar]
  95. AboelellaN.S. BrandleC. KimT. DingZ.C. ZhouG. Oxidative stress in the tumor microenvironment and its relevance to cancer immunotherapy.Cancers202113598610.3390/cancers1305098633673398
     [Google Scholar]
  96. ZhangQ. HanZ. ZhuY. ChenJ. LiW. Role of hypoxia inducible factor-1 in cancer stem cells (Review).Mol. Med. Rep.20212311733179080
     [Google Scholar]
  97. LiY. ChenZ. GuL. DuanZ. PanD. XuZ. GongQ. LiY. ZhuH. LuoK. Anticancer nanomedicines harnessing tumor microenvironmental components.Expert Opin. Drug Deliv.202219433735410.1080/17425247.2022.205021135244503
     [Google Scholar]
  98. DuyaP.A. ChenY. BaiL. LiZ. LiJ. ChaiR. BianY. ZhaoS. Nature products of traditional Chinese medicine provide new ideas in γδT cell for tumor immunotherapy.Acupunct. Herb. Med.202222788310.1097/HM9.0000000000000032
     [Google Scholar]
  99. LeeD.S. OhK. Cancer stem cells in the immune microenvironment.Adv. Exp. Med. Biol.2021118724526610.1007/978‑981‑32‑9620‑6_1233983582
     [Google Scholar]
  100. NakataK. MaizelJ.V.Jr Prediction of operator-binding protein by discriminant analysis.Gene Anal. Tech.19896611111910.1016/0735‑0651(89)90001‑02606442
     [Google Scholar]
  101. WonM. KimJ.H. JiM.S. KimJ.S. ROS activated prodrug for ALDH overexpressed cancer stem cells.Chem. Commun.2021581727510.1039/D1CC05573A34874378
     [Google Scholar]
  102. BarrecaD. Mechanisms of plant antioxidants action.Plants20201013510.3390/plants1001003533375600
     [Google Scholar]
  103. GeorgeS. AbrahamseH. Redox potential of antioxidants in cancer progression and prevention.Antioxidants2020911115610.3390/antiox911115633233630
     [Google Scholar]
  104. QuL. LiuC. KeC. ZhanX. LiL. XuH. XuK. LiuY. Atractylodes lancea rhizoma attenuates DSS-induced colitis by regulating intestinal flora and metabolites.Am. J. Chin. Med.202250252555210.1142/S0192415X2250020335114907
     [Google Scholar]
  105. QuL. ShiK. XuJ. LiuC. KeC. ZhanX. XuK. LiuY. Atractylenolide-1 targets SPHK1 and B4GALT2 to regulate intestinal metabolism and flora composition to improve inflammation in mice with colitis.Phytomedicine20229815394510.1016/j.phymed.2022.15394535114452
     [Google Scholar]
  106. WangZ. LiL. WangS. WeiJ. QuL. PanL. XuK. The role of the gut microbiota and probiotics associated with microbial metabolisms in cancer prevention and therapy.Front. Pharmacol.202213102586010.3389/fphar.2022.102586036452234
     [Google Scholar]
  107. MengD.F. GuoL.L. PengL.X. ZhengL.S. XieP. MeiY. LiC.Z. PengX.S. LangY.H. LiuZ.J. WangM.D. XieD.H. ShuD.T. HuH. LinS.T. LiH.F. LuoF.F. SunR. HuangB.J. QianC.N. Antioxidants suppress radiation-induced apoptosis via inhibiting MAPK pathway in nasopharyngeal carcinoma cells.Biochem. Biophys. Res. Commun.2020527377077710.1016/j.bbrc.2020.04.09332446561
     [Google Scholar]
  108. PanL. FengF. WuJ. LiL. XuH. YangL. XuK. WangC. Diosmetin inhibits cell growth and proliferation by regulating the cell cycle and lipid metabolism pathway in hepatocellular carcinoma.Food Funct.20211223120361204610.1039/D1FO02111G34755740
     [Google Scholar]
  109. HuA. QiuR. LiW.B. Radical recombination and antioxidants: A hypothesis on the FLASH effect mechanism.Int. J. Radiat. Biol.202299462062835938944
     [Google Scholar]
  110. KimD. IlleperumaR.P. KimJ. The protective effect of antioxidants in areca nut extract-induced oral carcinogenesis.Asian Pac. J. Cancer Prev.20202182447245210.31557/APJCP.2020.21.8.244732856877
     [Google Scholar]
  111. WangH. WangQ. DongJ. JiangW. KongL. ZhangQ. LiuH. New perspective of ceria nanodots for precise tumor therapy via oxidative stress pathway.Heliyon202288e1037010.1016/j.heliyon.2022.e1037036061010
     [Google Scholar]
  112. PetriA. AlexandratouE. YovaD. Assessment of natural antioxidants’ effect on PDT cytotoxicity through fluorescence microscopy image analysis.Lasers Surg. Med.202254231131910.1002/lsm.2346934431540
     [Google Scholar]
  113. ShinH.J. HanJ.M. ChoiY.S. JungH.J. Pterostilbene suppresses both cancer cells and cancer stem-like cells in cervical cancer with superior bioavailability to resveratrol.Molecules202025122810.3390/molecules2501022831935877
     [Google Scholar]
  114. LiG. FangS. ShaoX. LiY. TongQ. KongB. ChenL. WangY. YangJ. YuH. XieX. ZhangJ. Curcumin reverses NNMT-induced 5-fluorouracil resistance via increasing ROS and cell cycle arrest in colorectal cancer cells.Biomolecules2021119129510.3390/biom1109129534572508
     [Google Scholar]
  115. ManQ. DengY. LiP. MaJ. YangZ. YangX. ZhouY. YanX. Licorice ameliorates cisplatin-induced hepatotoxicity through antiapoptosis, antioxidative stress, anti-inflammation, and acceleration of metabolism.Front. Pharmacol.20201156375010.3389/fphar.2020.56375033240085
     [Google Scholar]
  116. KangD.Y. SpN. JangK.J. JoE.S. BaeS.W. YangY.M. Antitumor effects of natural bioactive ursolic acid in embryonic cancer stem cells.J. Oncol.2022202211010.1155/2022/673724835222644
     [Google Scholar]
  117. FuM. LiuY. ChengH. XuK. WangG. Coptis chinensis and dried ginger herb combination inhibits gastric tumor growth by interfering with glucose metabolism via LDHA and SLC2A1.J. Ethnopharmacol.202228411477110.1016/j.jep.2021.11477134737010
     [Google Scholar]
  118. ZhangX. HuB. SunY.F. HuangX.W. ChengJ.W. HuangA. ZengH.Y. QiuS.J. CaoY. FanJ. ZhouJ. YangX.R. Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF‐kB signaling pathways synergistically.Clin. Transl. Med.2021112e33510.1002/ctm2.33533634982
     [Google Scholar]
  119. XuH. LiL. QuL. Atractylenolide-1 affects glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI to inhibit the proliferation and invasion of human triple-negative breast cancer cells.Phytother. Res.202337382083336420870
     [Google Scholar]
  120. GhufranH. AzamM. MehmoodA. AshfaqR. BaigM.T. MalikK. ShahidA.A. RiazuddinS. Tumoricidal effects of unprimed and curcumin-primed adipose-derived stem cells on human hepatoma HepG2 cells under oxidative conditions.Tissue Cell20227910196810.1016/j.tice.2022.10196836356560
     [Google Scholar]
  121. LiH. HeM. ZhaoP. LiuP. ChenW. XuX. Chelerythrine chloride inhibits stemness of melanoma cancer stem-like cells (CSCs) potentially via inducing reactive oxygen species and causing mitochondria dysfunction.Comput. Math. Methods Med.2022202211010.1155/2022/400073335761835
     [Google Scholar]
  122. AlamM.A. Anti-hypertensive effect of cereal antioxidant ferulic acid and its mechanism of action.Front. Nutr.2019612110.3389/fnut.2019.0012131448280
     [Google Scholar]
  123. VenugopalK. RatherH.A. RajagopalK. ShanthiM.P. SheriffK. IlliyasM. RatherR.A. ManikandanE. UvarajanS. BhaskarM. MaazaM. Synthesis of silver nanoparticles (Ag NPs) for anticancer activities (MCF 7 breast and A549 lung cell lines) of the crude extract of Syzygium aromaticum.J. Photochem. Photobiol. B201716728228910.1016/j.jphotobiol.2016.12.01328110253
     [Google Scholar]
  124. ZhaoH. GuoJ. ChiQ. FangM. Molecular mechanisms of tanshinone IIA in Hepatocellular carcinoma therapy via WGCNA-based network pharmacology analysis.Biocell20224651245125910.32604/biocell.2022.018117
     [Google Scholar]
  125. ZhuP. FanZ. Cancer stem cells and tumorigenesis.Biophys. Rep.20184417818810.1007/s41048‑018‑0062‑230310855
     [Google Scholar]
  126. LeungH.W. KoC.H. YueG.G.L. HerrI. LauC.B.S. The natural agent 4-vinylphenol targets metastasis and stemness features in breast cancer stem-like cells.Cancer Chemother. Pharmacol.201882218519710.1007/s00280‑018‑3601‑029777274
     [Google Scholar]
  127. BarzegariA. NouriM. GueguenV. SaeediN. DjavidP.G. OmidiY. Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells.J. Cell. Physiol.20202357-85628563610.1002/jcp.2949531989645
     [Google Scholar]
  128. PadhyD. SharmaS. SinghS. Andrographolide protect against lipopolysacharides induced vascular endothelium dysfunction by abrogation of oxidative stress and chronic inflammation in Sprague–Dawley rats.J. Biochem. Mol. Toxicol.2024381e2363210.1002/jbt.2363238229310
     [Google Scholar]
  129. WangC. WangS. WangZ. HanJ. JiangN. QuL. XuK. Andrographolide regulates H3 histone lactylation by interfering with p300 to alleviate aortic valve calcification.Br. J. Pharmacol.2024bph.1633210.1111/bph.1633238378175
     [Google Scholar]
  130. WangH. HaridasV. GuttermanJ.U. XuZ.X. Natural triterpenoid avicins selectively induce tumor cell death.Commun. Integr. Biol.20103320520810.4161/cib.3.3.1149220714394
     [Google Scholar]
  131. IssaM.E. BerndtS. CarpentierG. PezzutoJ.M. CuendetM. Bruceantin inhibits multiple myeloma cancer stem cell proliferation.Cancer Biol. Ther.201617996697510.1080/15384047.2016.121073727434731
     [Google Scholar]
  132. FengF. PanL. WuJ. LiL. XuH. YangL. XuK. WangC. Cepharanthine inhibits hepatocellular carcinoma cell growth and proliferation by regulating amino acid metabolism and suppresses tumorigenesis in vivo.Int. J. Biol. Sci.202117154340435210.7150/ijbs.6467534803502
     [Google Scholar]
  133. ZhuZ. PanH. LiY. PanW. Evaluation of the synergism mechanism of tamoxifen and docetaxel by nanoparticles.Anticancer. Agents Med. Chem.202019161991200010.2174/187152061966619070212082931267877
     [Google Scholar]
  134. PanL. FengF. WuJ. FanS. HanJ. WangS. YangL. LiuW. WangC. XuK. Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells.Pharmacol. Res.202218110627010.1016/j.phrs.2022.10627035605812
     [Google Scholar]
  135. WangH. LiuX. LongM. HuangY. ZhangL. ZhangR. ZhengY. LiaoX. WangY. LiaoQ. LiW. TangZ. TongQ. WangX. FangF. de la VegaM.R. OuyangQ. ZhangD.D. YuS. ZhengH. NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis.Sci. Transl. Med.20168334334ra5110.1126/scitranslmed.aad609527075625
     [Google Scholar]
  136. XuH. LiL. WangS. WangZ. QuL. WangC. XuK. Royal jelly acid suppresses hepatocellular carcinoma tumorigenicity by inhibiting H3 histone lactylation at H3K9la and H3K14la sites.Phytomedicine202311815494010.1016/j.phymed.2023.15494037453194
     [Google Scholar]
  137. ManogaranP. SomasundaramB. ViswanadhaV.P. Reversal of cisplatin resistance by neferine/isoliensinine and their combinatorial regimens with cisplatin‐induced apoptosis in cisplatin‐resistant colon cancer stem cells (CSCs).J. Biochem. Mol. Toxicol.2022363e2296710.1002/jbt.2296734921482
     [Google Scholar]
  138. LiuS. WangJ. ShaoT. SongP. KongQ. HuaH. LuoT. JiangY. The natural agent rhein induces β‐catenin degradation and tumour growth arrest.J. Cell. Mol. Med.201822158959910.1111/jcmm.1334629024409
     [Google Scholar]
  139. LiL. XuH. QuL. NisarM. Farrukh NisarM. LiuX. XuK. Water extracts of Polygonum Multiflorum Thunb. and its active component emodin relieves osteoarthritis by regulating cholesterol metabolism and suppressing chondrocyte inflammation.Acupunct. Herb. Med.2023329610610.1097/HM9.0000000000000061
     [Google Scholar]
  140. SemwalR.B. SemwalD.K. CombrinckS. ViljoenA. Emodin - A natural anthraquinone derivative with diverse pharmacological activities.Phytochemistry202119011285410.1016/j.phytochem.2021.11285434311280
     [Google Scholar]
  141. ArafaE.S.A. HassaneinE.H.M. IbrahimN.A. BuabeidM.A. MohamedW.R. Involvement of Nrf2-PPAR-γ signaling in Coenzyme Q10 protecting effect against methotrexate-induced testicular oxidative damage.Int. Immunopharmacol.202412911156610.1016/j.intimp.2024.11156638364740
     [Google Scholar]
  142. CelikA. AtesB.F. Alpha-lipoic acid induced apoptosis of PC3 prostate cancer cells through an alteration on mitochondrial membrane depolarization and MMP-9 mRNA expression.Med. Oncol.202340824410.1007/s12032‑023‑02113‑737453954
     [Google Scholar]
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Targeted Therapy of Tumors and Cancer Stem Cells based on Oxidant-regulated Redox Pathway and its Mechanism
Curr. Computeraided Drug Des. 21, 425 (2025); https://doi.org/10.2174/0115734099299174240522115944
/content/journals/cad/10.2174/0115734099299174240522115944
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  • Article Type:     Review Article
Keyword(s): Cancer stem cell; cell signaling pathway; oxidation reduction pathway; oxidative stress; oxidizing agent; ROS

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