Skip to content
2000
image of Targeted Therapy of Tumors and Cancer Stem Cells based on Oxidant-regulated Redox Pathway and its Mechanism

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.

Loading

Article metrics loading...

/content/journals/cad/10.2174/0115734099299174240522115944
2024-05-30
2025-01-18
Loading full text...

Full text loading...

References

  1. Cao W. Chen H.D. Yu Y.W. Li N. Chen W.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J. 2021 134 7 783 791 10.1097/CM9.0000000000001474 33734139
    [Google Scholar]
  2. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  3. Li Z. Feiyue Z. Gaofeng L. Traditional Chinese medicine and lung cancer——From theory to practice. Biomed. Pharmacother. 2021 137 111381 10.1016/j.biopha.2021.111381 33601147
    [Google Scholar]
  4. Zhang X. Qiu H. Li C. Cai P. Qi F. The positive role of traditional Chinese medicine as an adjunctive therapy for cancer. Biosci. Trends 2021 15 5 283 298 10.5582/bst.2021.01318 34421064
    [Google Scholar]
  5. Zhang Y. Lou Y. Wang J. Yu C. Shen W. Research status and molecular mechanism of the traditional chinese medicine and antitumor therapy combined strategy based on tumor microenvironment. Front. Immunol. 2021 11 609705 10.3389/fimmu.2020.609705 33552068
    [Google Scholar]
  6. Ota N. Yoshimoto Y. Darwis N.D.M. Sato H. Ando K. Oike T. Ohno T. High tumor mutational burden predicts worse prognosis for cervical cancer treated with radiotherapy. Jpn. J. Radiol. 2022 40 5 534 541 10.1007/s11604‑021‑01230‑5 34860358
    [Google Scholar]
  7. Arneth B. Tumor microenvironment. Medicina (B. Aires) 2019 56 1 15 10.3390/medicina56010015 31906017
    [Google Scholar]
  8. Eckerdt F.D. Bell J.B. Gonzalez C. Oh M.S. Perez R.E. Mazewski C. Fischietti M. Goldman S. Nakano I. Platanias L.C. Combined PI3Kα-mTOR targeting of glioma stem cells. Sci. Rep. 2020 10 1 21873 10.1038/s41598‑020‑78788‑z 33318517
    [Google Scholar]
  9. Lendeckel U. Wolke C. Redox-regulation in cancer stem cells. Biomedicines 2022 10 10 2413 10.3390/biomedicines10102413 36289675
    [Google Scholar]
  10. Najafi M. Farhood B. Mortezaee K. Cancer stem cells (CSCs) in cancer progression and therapy. J. Cell. Physiol. 2019 234 6 8381 8395 10.1002/jcp.27740 30417375
    [Google Scholar]
  11. Wang Y.Y. Wang W.D. Sun Z.J. Cancer stem cell‐immune cell collusion in immunotherapy. Int. J. Cancer 2023 153 4 694 708 10.1002/ijc.34421 36602290
    [Google Scholar]
  12. Bayik D. Lathia J.D. Cancer stem cell–immune cell crosstalk in tumour progression. Nat. Rev. Cancer 2021 21 8 526 536 10.1038/s41568‑021‑00366‑w 34103704
    [Google Scholar]
  13. Xiao Y. Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol. Ther. 2021 221 107753 10.1016/j.pharmthera.2020.107753 33259885
    [Google Scholar]
  14. Chinn S.B. Darr O.A. Owen J.H. Bellile E. McHugh J.B. Spector M.E. Papagerakis S.M. Chepeha D.B. Bradford C.R. Carey T.E. Prince M.E.P. Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma. Head Neck 2015 37 3 317 326 10.1002/hed.23600 24415402
    [Google Scholar]
  15. Wang S. Ma S. Li X. Xue Z. Zhang X. Fan W. Nie Y. Wu K. Chen X. Cao F. Attenuation of lung cancer stem cell tumorigenesis and metastasis by cisplatin. Exp. Lung Res. 2014 40 8 404 414 10.3109/01902148.2014.938201 25153512
    [Google Scholar]
  16. Wiwanitkit V. Oxidative stress and metabolic syndrome. Korean J. Fam. Med. 2014 35 1 44 10.4082/kjfm.2014.35.1.44 24501670
    [Google Scholar]
  17. Watson J.D. Type 2 diabetes as a redox disease. Lancet 2014 383 9919 841 843 10.1016/S0140‑6736(13)62365‑X 24581668
    [Google Scholar]
  18. Prakash R. Fauzia E. Siddiqui A.J. Yadav S.K. Kumari N. Shams M.T. Naeem A. Praharaj P.P. Khan M.A. Bhutia S.K. Janowski M. Boltze J. Raza S.S. Oxidative stress-induced autophagy compromises stem cell viability. Stem Cells 2022 40 5 468 478 10.1093/stmcls/sxac018 35294968
    [Google Scholar]
  19. Reczek C.R. Chandel N.S. ROS promotes cancer cell survival through calcium signaling. Cancer Cell 2018 33 6 949 951 10.1016/j.ccell.2018.05.010 29894695
    [Google Scholar]
  20. Gorrini C. Harris I.S. Mak T.W. Modulation of oxidative stress as an anticancer strategy. Nat. Rev. Drug Discov. 2013 12 12 931 947 10.1038/nrd4002 24287781
    [Google Scholar]
  21. Wiel C. Le Gal K. Ibrahim M.X. Jahangir C.A. Kashif M. Yao H. Ziegler D.V. Xu X. Ghosh T. Mondal T. Kanduri C. Lindahl P. Sayin V.I. Bergo M.O. BACH1 stabilization by antioxidants stimulates lung cancer metastasis. Cell 2019 178 2 330 345.e22 10.1016/j.cell.2019.06.005 31257027
    [Google Scholar]
  22. Wang W. Sun H. Che Y. Jiang X. Rasfonin promotes autophagy and apoptosis via upregulation of reactive oxygen species (ROS)/JNK pathway. Mycology 2016 7 2 64 73 10.1080/21501203.2016.1170073 30123617
    [Google Scholar]
  23. Bhuyan S. Pal B. Pathak L. Saikia P.J. Mitra S. Gayan S. Mokhtari R.B. Li H. Ramana C.V. Baishya D. Das B. Targeting hypoxia-induced tumor stemness by activating pathogen-induced stem cell niche defense. Front. Immunol. 2022 13 933329 10.3389/fimmu.2022.933329 36248858
    [Google Scholar]
  24. Lapidot T. Sirard C. Vormoor J. Murdoch B. Hoang T. Cortes C.J. Minden M. Paterson B. Caligiuri M.A. Dick J.E. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994 367 6464 645 648 10.1038/367645a0 7509044
    [Google Scholar]
  25. Al-Hajj M. Wicha M.S. Hernandez B.A. Morrison S.J. Clarke M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 2003 100 7 3983 3988 10.1073/pnas.0530291100 12629218
    [Google Scholar]
  26. Meuwissen K.P.V. Gu J.W. Zhang T.C. Joosten E.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. Neuromodulation 2018 21 1 19 30 10.1111/ner.12731 29178358
    [Google Scholar]
  27. Gao W. Xu S. Zhang M. Liu S. Siu S.P. Peng H. Ng J.C. Tsao G.S. Chan A.W. Chow V.L. Chan J.Y. Wong T.S. NADPH oxidase 5α promotes the formation of CD271 tumor-initiating cells in oral cancer. Am. J. Cancer Res. 2020 10 6 1710 1727 32642285
    [Google Scholar]
  28. Alvina F.B. Gouw A.M. Le A. Cancer stem cell metabolism. Adv. Exp. Med. Biol. 2021 1311 161 172 10.1007/978‑3‑030‑65768‑0_12 34014542
    [Google Scholar]
  29. Tu Y. Zhou Y. Zhang D. Yang J. Li X. Ji K. Wu X. Liu R. Zhang Q. 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. 2021 4 6 5222 5230 10.1021/acsabm.1c00386 35007004
    [Google Scholar]
  30. Čipak Gašparović A. Milković L. Dandachi N. Stanzer S. Pezdirc I. Vrančić J. Šitić S. Suppan C. Balic M. Chronic oxidative stress promotes molecular changes associated with epithelial mesenchymal transition, NRF2, and breast cancer stem cell phenotype. Antioxidants 2019 8 12 633 10.3390/antiox8120633 31835715
    [Google Scholar]
  31. van der Post S. Birchenough G.M.H. Held J.M. NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation. Cell Rep. 2021 35 1 108949 10.1016/j.celrep.2021.108949 33826887
    [Google Scholar]
  32. Chen K. Pan F. Jiang H. Chen J. Pei L. Xie F. Liang H. Highly enriched CD133+CD44+ stem-like cells with CD133+CD44high metastatic subset in HCT116 colon cancer cells. Clin. Exp. Metastasis 2011 28 8 751 763 10.1007/s10585‑011‑9407‑7 21750907
    [Google Scholar]
  33. He A. Yang X. Huang Y. Feng T. Wang Y. Sun Y. Shen Z. Yao Y. CD133 + CD44 + cells mediate in the lung metastasis of osteosarcoma. J. Cell. Biochem. 2015 116 8 1719 1729 10.1002/jcb.25131 25736420
    [Google Scholar]
  34. Liang W. Luo Q. Zhang Z. Yang K. Yang A. Chi Q. Hu H. An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1, pathways and immune infiltration in diabetic nephropathy mice. Biocell 2022 46 8 1989 2002 10.32604/biocell.2022.019300
    [Google Scholar]
  35. Xu R. Wu Q. Gong Y. Wu Y. Chi Q. Sun D. A novel prognostic target-gene signature and nomogram based on an integrated bioinformatics analysis in hepatocellular carcinoma. Biocell 2022 46 5 1261 1288 10.32604/biocell.2022.018427
    [Google Scholar]
  36. Fang M. Guo J. Wang H. Yang Z. Zhao H. Chi Q. WGCNA and LASSO algorithm constructed an immune infiltration-related 5-gene signature and nomogram to improve prognosis prediction of hepatocellular carcinoma. Biocell 2022 46 2 401 415 10.32604/biocell.2022.016989
    [Google Scholar]
  37. Tian F. Hu H. Wang D. Ding H. Chi Q. Liang H. Zeng W. Immune-related DNA methylation signature associated with APLN expression predicts prognostic of hepatocellular carcinoma. Biocell 2022 46 10 2291 2301 10.32604/biocell.2022.020198
    [Google Scholar]
  38. Lv S. An Y. Dong H. Xie L. Zheng H. Cheng X. Zhang L. Teng T. Wang Q. Yan Z. Guo X. High APLN expression predicts poor prognosis for glioma patients. Oxid. Med. Cell. Longev. 2022 2022 1 16 10.1155/2022/8393336 36193059
    [Google Scholar]
  39. Huang R. Rofstad E.K. Cancer stem cells (CSCs), cervical CSCs and targeted therapies. Oncotarget 2017 8 21 35351 35367 10.18632/oncotarget.10169 27343550
    [Google Scholar]
  40. Zhang J. Wang X. Vikash V. Ye Q. Wu D. Liu Y. Dong W. ROS and ROS-mediated cellular signaling. Oxid. Med. Cell. Longev. 2016 2016 1 18 10.1155/2016/4350965 26998193
    [Google Scholar]
  41. Zorov D.B. Juhaszova M. Sollott S.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 2014 94 3 909 950 10.1152/physrev.00026.2013 24987008
    [Google Scholar]
  42. Yu L. Lu M. Jia D. Ma J. Ben-Jacob E. Levine H. Kaipparettu B.A. Onuchic J.N. Modeling the genetic regulation of cancer metabolism: Interplay between glycolysis and oxidative phosphorylation. Cancer Res. 2017 77 7 1564 1574 10.1158/0008‑5472.CAN‑16‑2074 28202516
    [Google Scholar]
  43. Polireddy K. Dong R. Reed G. Yu J. Chen P. Williamson S. Violet P.C. Pessetto Z. Godwin A.K. Fan F. Levine M. Drisko J.A. Chen Q. High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: Mechanisms and a phase I/IIa study. Sci. Rep. 2017 7 1 17188 10.1038/s41598‑017‑17568‑8 29215048
    [Google Scholar]
  44. Su X. Shen Z. Yang Q. Sui F. Pu J. Ma J. Ma S. Yao D. Ji M. Hou P. Vitamin C kills thyroid cancer cells through ROS-dependent inhibition of MAPK/ERK and PI3K/AKT pathways via distinct mechanisms. Theranostics 2019 9 15 4461 4473 10.7150/thno.35219 31285773
    [Google Scholar]
  45. Tang X.H. Gudas L.J. Retinoids, retinoic acid receptors, and cancer. Annu. Rev. Pathol. 2011 6 1 345 364 10.1146/annurev‑pathol‑011110‑130303 21073338
    [Google Scholar]
  46. Suraweera L. T.; Rupasinghe, H.P.V.; Dellaire, G.; Xu, Z. Regulation of Nrf2/ARE pathway by dietary flavonoids: A friend or foe for cancer management? Antioxidants 2020 9 10 973 10.3390/antiox9100973 33050575
    [Google Scholar]
  47. Metcalfe N.B. Olsson M. How telomere dynamics are influenced by the balance between mitochondrial efficiency, reactive oxygen species production and DNA damage. Mol. Ecol. 2022 31 23 6040 6052 34435398
    [Google Scholar]
  48. Castelli S. Ciccarone F. De Falco P. Ciriolo M.R. Adaptive antioxidant response to mitochondrial fatty acid oxidation determines the proliferative outcome of cancer cells. Cancer Lett. 2023 554 216010 10.1016/j.canlet.2022.216010 36402229
    [Google Scholar]
  49. Zheng Y.L. Tu Z.S. Cui H.M. Yan S. Duan D.C. Tang W. Dai F. Zhou B. Redox-based strategy for selectively inducing energy crisis inside cancer cells: An example of modifying dietary curcumin to target mitochondria. J. Agric. Food Chem. 2022 70 9 2898 2910 10.1021/acs.jafc.1c07690 35213152
    [Google Scholar]
  50. Choromańska B. Myśliwiec P. Kozłowski T. Łukaszewicz J. Vasilyevich H.P. Dadan J. Zalewska A. Maciejczyk M. Antioxidant and antiradical activities depend on adrenal tumor type. Front. Endocrinol. 2022 13 1011043 10.3389/fendo.2022.1011043 36246875
    [Google Scholar]
  51. Patil T. Rohiwal S.S. Tiwari A.P. Stem cells: Therapeutic implications in chemotherapy and radiotherapy resistance in cancer therapy. Curr. Stem Cell Res. Ther. 2023 18 6 750 765 10.2174/1574888X17666221003125208 36200212
    [Google Scholar]
  52. Ramos A. dos Santos M.M. de Macedo G.T. Wildner G. Prestes A.S. Masuda C.A. Corte D.C.L. da Rocha T.J.B. Barbosa N.V. Methyl and ethylmercury elicit oxidative stress and unbalance the antioxidant system in saccharomyces cerevisiae. Chem. Biol. Interact. 2020 315 108867 10.1016/j.cbi.2019.108867 31672467
    [Google Scholar]
  53. Feng J. Zhao D. Lv F. Yuan Z. Epigenetic inheritance from normal origin cells can determine the aggressive biology of tumor-initiating cells and tumor heterogeneity. Cancer Contr. 2022 29 10.1177/10732748221078160 35213254
    [Google Scholar]
  54. Galluzzi L. Vitale I. Aaronson S.A. Abrams J.M. Adam D. Agostinis P. Alnemri E.S. Altucci L. Amelio I. Andrews D.W. Petruzzelli A.M. Antonov A.V. Arama E. Baehrecke E.H. Barlev N.A. Bazan N.G. Bernassola F. Bertrand M.J.M. Bianchi K. Blagosklonny M.V. Blomgren K. Borner C. Boya P. Brenner C. Campanella M. Candi E. Gutierrez C.D. Cecconi F. Chan F.K.M. Chandel N.S. Cheng E.H. Chipuk J.E. Cidlowski J.A. Ciechanover A. Cohen G.M. Conrad M. Ruiz C.J.R. Czabotar P.E. D’Angiolella V. Dawson T.M. Dawson V.L. De Laurenzi V. De Maria R. Debatin K.M. DeBerardinis R.J. Deshmukh M. Daniele D.N. Virgilio D.F. Dixit V.M. Dixon S.J. Duckett C.S. Dynlacht B.D. El-Deiry W.S. Elrod J.W. Fimia G.M. Fulda S. Sáez G.A.J. Garg A.D. Garrido C. Gavathiotis E. Golstein P. Gottlieb E. Green D.R. Greene L.A. Gronemeyer H. Gross A. Hajnoczky G. Hardwick J.M. Harris I.S. Hengartner M.O. Hetz C. Ichijo H. Jäättelä M. Joseph B. Jost P.J. Juin P.P. Kaiser W.J. Karin M. Kaufmann T. Kepp O. Kimchi A. Kitsis R.N. Klionsky D.J. Knight R.A. Kumar S. Lee S.W. Lemasters J.J. Levine B. Linkermann A. Lipton S.A. Lockshin R.A. López-Otín C. Lowe S.W. Luedde T. Lugli E. MacFarlane M. Madeo F. Malewicz M. Malorni W. Manic G. Marine J.C. Martin S.J. Martinou J.C. Medema J.P. Mehlen P. Meier P. Melino S. Miao E.A. Molkentin J.D. Moll U.M. Muñoz-Pinedo C. Nagata S. Nuñez G. Oberst A. Oren M. Overholtzer M. Pagano M. Panaretakis T. Pasparakis M. Penninger J.M. Pereira D.M. Pervaiz S. Peter M.E. Piacentini M. Pinton P. Prehn J.H.M. Puthalakath H. Rabinovich G.A. Rehm M. Rizzuto R. Rodrigues C.M.P. Rubinsztein D.C. Rudel T. Ryan K.M. Sayan E. Scorrano L. Shao F. Shi Y. Silke J. Simon H.U. Sistigu A. Stockwell B.R. Strasser A. Szabadkai G. Tait S.W.G. Tang D. Tavernarakis N. Thorburn A. Tsujimoto Y. Turk B. Berghe V.T. Vandenabeele P. Heiden V.M.G. Villunger A. Virgin H.W. Vousden K.H. Vucic D. Wagner E.F. Walczak H. Wallach D. Wang Y. Wells J.A. Wood W. Yuan J. Zakeri Z. Zhivotovsky B. Zitvogel L. Melino G. Kroemer G. Molecular mechanisms of cell death: Recommendations of the nomenclature committee on cell death 2018. Cell Death Differ. 2018 25 3 486 541 10.1038/s41418‑017‑0012‑4 29362479
    [Google Scholar]
  55. Chen Y. Ohara T. Xing B. Qi J. Noma K. Matsukawa A. A promising new anti-cancer strategy: Iron chelators targeting CSCs. Acta Med. Okayama 2020 74 1 1 6 32099242
    [Google Scholar]
  56. Jiang Y. Huo Z. Qi X. Zuo T. Wu Z. Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes. Nanomedicine 2022 17 5 303 324 10.2217/nnm‑2021‑0374 35060391
    [Google Scholar]
  57. Jeong S.D. Jung B.K. Lee D. Ha J. Chang H.G. Lee J. Lee S. Yun C.O. Kim Y.C. Enhanced immunogenic cell death by apoptosis/ferroptosis hybrid pathway potentiates pd-l1 blockade cancer immunotherapy. ACS Biomater. Sci. Eng. 2022 8 12 5188 5198 10.1021/acsbiomaterials.2c00950 36449494
    [Google Scholar]
  58. Huang S. Chen Y. Hu Y. Shi Y. Xiao Q. Li Z. Kang J. Zhou Q. Shen G. Jia H. Downregulation of MCF2L promoted the ferroptosis of hepatocellular carcinoma cells through PI3K/mTOR pathway in a RhoA/Rac1 dependent manner. Dis. Markers 2022 2022 1 13 10.1155/2022/6138941 36330204
    [Google Scholar]
  59. Li X. Zeng J. Liu Y. Liang M. Liu Q. Li Z. Zhao X. Chen D. 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. Antioxidants 2020 9 3 205 10.3390/antiox9030205 32131401
    [Google Scholar]
  60. Zhou D. Shao L. Spitz D.R. Reactive oxygen species in normal and tumor stem cells. Adv. Cancer Res. 2014 122 1 67 10.1016/B978‑0‑12‑420117‑0.00001‑3 24974178
    [Google Scholar]
  61. Wang L. Liu Y. Du T. Yang H. Lei L. Guo M. Ding H.F. Zhang J. Wang H. Chen X. Yan C. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc–. Cell Death Differ. 2020 27 2 662 675 10.1038/s41418‑019‑0380‑z 31273299
    [Google Scholar]
  62. Lei G. Zhang Y. Hong T. Zhang X. Liu X. Mao C. Yan Y. Koppula P. Cheng W. Sood A.K. Liu J. Gan B. Ferroptosis as a mechanism to mediate p53 function in tumor radiosensitivity. Oncogene 2021 40 20 3533 3547 10.1038/s41388‑021‑01790‑w 33927351
    [Google Scholar]
  63. Ishimoto T. Nagano O. Yae T. Tamada M. Motohara T. Oshima H. Oshima M. Ikeda T. Asaba R. Yagi H. Masuko T. Shimizu T. Ishikawa T. Kai K. Takahashi E. Imamura Y. Baba Y. Ohmura M. Suematsu M. Baba H. Saya H. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell 2011 19 3 387 400 10.1016/j.ccr.2011.01.038 21397861
    [Google Scholar]
  64. Begicevic R.R. Arfuso F. Falasca M. Bioactive lipids in cancer stem cells. World J. Stem Cells 2019 11 9 693 704 10.4252/wjsc.v11.i9.693 31616544
    [Google Scholar]
  65. Xu X. Zhang X. Wei C. Zheng D. Lu X. Yang Y. Luo A. Zhang K. Duan X. Wang Y. Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis. Eur. J. Pharm. Sci. 2020 152 105450 10.1016/j.ejps.2020.105450 32621966
    [Google Scholar]
  66. Wu Q. Needs P.W. Lu Y. Kroon P.A. Ren D. Yang X. Different antitumor effects of quercetin, quercetin-3′-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Funct. 2018 9 3 1736 1746 10.1039/C7FO01964E 29497723
    [Google Scholar]
  67. Dodson M. Anandhan A. Zhang D.D. Madhavan L. An NRF2 perspective on stem cells and ageing. Front. Aging 2021 2 690686 10.3389/fragi.2021.690686 36213179
    [Google Scholar]
  68. Kansanen E. Kuosmanen S.M. Leinonen H. Levonen A.L. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol. 2013 1 1 45 49 10.1016/j.redox.2012.10.001 24024136
    [Google Scholar]
  69. Li X. He S. Zhou J. Yu X. Li L. Liu Y. Li W. Cr (VI) induces abnormalities in glucose and lipid metabolism through ROS/Nrf2 signaling. Ecotoxicol. Environ. Saf. 2021 219 112320 10.1016/j.ecoenv.2021.112320 33991932
    [Google Scholar]
  70. Wu T. Harder B.G. Wong P.K. Lang J.E. Zhang D.D. Oxidative stress, mammospheres and Nrf2–new implication for breast cancer therapy? Mol. Carcinog. 2015 54 11 1494 1502 10.1002/mc.22202 25154499
    [Google Scholar]
  71. Muri J. Kopf M. The thioredoxin system: Balancing redox responses in immune cells and tumors. Eur. J. Immunol. 2023 53 1 2249948 36285367
    [Google Scholar]
  72. Huang Y. Li W. Su Z. Kong A.N.T. The complexity of the Nrf2 pathway: Beyond the antioxidant response. J. Nutr. Biochem. 2015 26 12 1401 1413 10.1016/j.jnutbio.2015.08.001 26419687
    [Google Scholar]
  73. Kubatka P. Mazurakova A. Samec M. Koklesova L. Zhai K. AL-Ishaq, R.; Kajo, K.; Biringer, K.; Vybohova, D.; Brockmueller, A.; Pec, M.; Shakibaei, M.; Giordano, F.A.; Büsselberg, D.; Golubnitschaja, O. Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression—3PM pathways. EPMA J. 2021 12 4 559 587 10.1007/s13167‑021‑00257‑y 34950252
    [Google Scholar]
  74. Kubo E. Chhunchha B. Singh P. Sasaki H. Singh D.P. Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress. Sci. Rep. 2017 7 1 14130 10.1038/s41598‑017‑14520‑8 29074861
    [Google Scholar]
  75. Pillai R. Hayashi M. Zavitsanou A.M. Papagiannakopoulos T. NRF2: KEAPing tumors protected. Cancer Discov. 2022 12 3 625 643 10.1158/2159‑8290.CD‑21‑0922 35101864
    [Google Scholar]
  76. Tsai K.J. Tsai H.Y. Tsai C.C. Chen T.Y. Hsieh T.H. Chen C.L. Mbuyisa L. Huang Y.B. Lin M.W. Luteolin inhibits breast cancer stemness and enhances chemosensitivity through the Nrf2-mediated pathway. Molecules 2021 26 21 6452 10.3390/molecules26216452 34770867
    [Google Scholar]
  77. Sun W. Meng J. Wang Z. Yuan T. Qian H. Chen W. Tong J. Xie Y. Zhang Y. Zhao J. Bao N. Proanthocyanidins attenuation of H 2 O 2 -induced oxidative damage in tendon-derived stem cells via upregulating nrf-2 signaling pathway. BioMed Res. Int. 2017 2017 1 8 10.1155/2017/7529104 29201913
    [Google Scholar]
  78. Xia P. Xu X.Y. PI3K/Akt/mTOR signaling pathway in cancer stem cells: From basic research to clinical application. Am. J. Cancer Res. 2015 5 5 1602 1609 26175931
    [Google Scholar]
  79. Ahmed E.S.A. Ahmed N.H. Medhat A.M. Said U.Z. Rashed L.A. Abdel Ghaffar A.R.B. Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model. Tumour Biol. 2019 41 4 10.1177/1010428319846803 31018830
    [Google Scholar]
  80. Park J. Kim S.K. Hallis S.P. Choi B.H. Kwak M.K. Role of CD133/NRF2 axis in the development of colon cancer stem cell-like properties. Front. Oncol. 2022 11 808300 10.3389/fonc.2021.808300 35155201
    [Google Scholar]
  81. Alipour F. Riyahi N. Azar S.A. Sari S. Zandi Z. Bashash D. Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO). Int. J. Biochem. Cell Biol. 2019 116 105615 10.1016/j.biocel.2019.105615 31539632
    [Google Scholar]
  82. Ouyang X. Shi X. Huang N. Yang Y. Zhao W. Guo W. Huang Y. WDR72 enhances the stemness of lung cancer cells by activating the AKT/HIF-1α signaling pathway. J. Oncol. 2022 2022 1 12 10.1155/2022/5059588 36385964
    [Google Scholar]
  83. de Winter T.J.J. Nusse R. Running against the Wnt: How Wnt/β-catenin suppresses adipogenesis. Front. Cell Dev. Biol. 2021 9 627429 10.3389/fcell.2021.627429 33634128
    [Google Scholar]
  84. Huang R. Zhang L. Jin J. Zhou Y. Zhang H. Lv C. Lu D. Wu Y. Zhang H. Liu S. Chen H. Luan X. Zhang W. Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction. Acta Pharm. Sin. B 2021 11 11 3481 3492 10.1016/j.apsb.2021.05.009 34900531
    [Google Scholar]
  85. Olmos Y. Gómez S.F.J. Wild B. Quintans G.N. Cabezudo S. Lamas S. Monsalve M. SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex. Antioxid. Redox Signal. 2013 19 13 1507 1521 10.1089/ars.2012.4713 23461683
    [Google Scholar]
  86. Zeng W. Ling F. Dang K. Chi Q. 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. Biocell 2023 47 3 581 592 10.32604/biocell.2023.025957
    [Google Scholar]
  87. Wei J. Marisetty A. Schrand B. Gabrusiewicz K. Hashimoto Y. Ott M. Grami Z. Kong L.Y. Ling X. Caruso H. Zhou S. Wang Y.A. Fuller G.N. Huse J. Gilboa E. Kang N. Huang X. Verhaak R. Li S. Heimberger A.B. Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target. J. Clin. Invest. 2018 129 1 137 149 10.1172/JCI121266 30307407
    [Google Scholar]
  88. Toscano V.A. Nickel A.C. Li G. Kamp M.A. Muhammad S. Leprivier G. Fritsche E. Barker R.A. Sabel M. Steiger H.J. Zhang W. Hänggi D. Kahlert U.D. Rapalink-1 targets glioblastoma stem cells and acts synergistically with tumor treating fields to reduce resistance against temozolomide. Cancers 2020 12 12 3859 10.3390/cancers12123859 33371210
    [Google Scholar]
  89. Viswanathan V. Opdenaker L. Modarai S. Fields J.Z. Gonye G. Boman B.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. 2020 21 8 2804 10.3390/ijms21082804 32316543
    [Google Scholar]
  90. Yuan D. Fang Y. Chen W. Jiang K. Zhu G. Wang W. Zhang W. You G. Jia Z. Zhu J. ZFP36 inhibits tumor progression of human prostate cancer by targeting CDK6 and oxidative stress. Oxid. Med. Cell. Longev. 2022 2022 1 24 10.1155/2022/3611540 36111167
    [Google Scholar]
  91. Krishna G. Pillai V.S. Gopi P. Epstein-Barr virus infection controls the concentration of the intracellular antioxidant glutathione by upregulation of the glutamate transporter EAAT3 in tumor cells. Virus Genes 2023 59 1 55 66 36344769
    [Google Scholar]
  92. Sun Q. Gui Z. Zhao Z. Xu W. Zhu J. Gao C. Zhao W. Hu H. Overexpression of LncRNA MNX1-AS1/PPFIA4 Activates AKT/HIF-1α Signal Pathway to Promote Stemness of Colorectal Adenocarcinoma Cells. J. Oncol. 2022 2022 1 16 10.1155/2022/8303409 36226248
    [Google Scholar]
  93. Luo M. Shang L. Brooks M.D. Jiagge E. Zhu Y. Buschhaus J.M. Conley S. Fath M.A. Davis A. Gheordunescu E. Wang Y. Harouaka R. Lozier A. Triner D. McDermott S. Merajver S.D. Luker G.D. Spitz D.R. Wicha M.S. Targeting breast cancer stem cell state equilibrium through modulation of redox signaling. Cell Metab. 2018 28 1 69 86.e6 10.1016/j.cmet.2018.06.006 29972798
    [Google Scholar]
  94. Dang H. Harryvan T.J. Hawinkels L.J.A.C. Fibroblast subsets in intestinal homeostasis, carcinogenesis, tumor progression, and metastasis. Cancers 2021 13 2 183 10.3390/cancers13020183 33430285
    [Google Scholar]
  95. Aboelella N.S. Brandle C. Kim T. Ding Z.C. Zhou G. Oxidative stress in the tumor microenvironment and its relevance to cancer immunotherapy. Cancers 2021 13 5 986 10.3390/cancers13050986 33673398
    [Google Scholar]
  96. Zhang Q. Han Z. Zhu Y. Chen J. Li W. Role of hypoxia inducible factor-1 in cancer stem cells. Mol. Med. Rep. 2021 23 1 17 33179080
    [Google Scholar]
  97. Li Y. Chen Z. Gu L. Duan Z. Pan D. Xu Z. Gong Q. Li Y. Zhu H. Luo K. Anticancer nanomedicines harnessing tumor microenvironmental components. Expert Opin. Drug Deliv. 2022 19 4 337 354 10.1080/17425247.2022.2050211 35244503
    [Google Scholar]
  98. Duya P.A. Chen Y. Bai L. Li Z. Li J. Chai R. Bian Y. Zhao S. Nature products of traditional Chinese medicine provide new ideas in γδT cell for tumor immunotherapy. Acupunct. Herb. Med. 2022 2 2 78 83 10.1097/HM9.0000000000000032
    [Google Scholar]
  99. Lee D.S. Oh K. Cancer stem cells in the immune microenvironment. Adv. Exp. Med. Biol. 2021 1187 245 266 10.1007/978‑981‑32‑9620‑6_12 33983582
    [Google Scholar]
  100. Nakata K. Maizel J.V. Jr Prediction of operator-binding protein by discriminant analysis. Gene Anal. Tech. 1989 6 6 111 119 10.1016/0735‑0651(89)90001‑0 2606442
    [Google Scholar]
  101. Won M. Kim J.H. Ji M.S. Kim J.S. ROS activated prodrug for ALDH overexpressed cancer stem cells. Chem. Commun. 2021 58 1 72 75 10.1039/D1CC05573A 34874378
    [Google Scholar]
  102. Barreca D. Mechanisms of plant antioxidants action. Plants 2020 10 1 35 10.3390/plants10010035 33375600
    [Google Scholar]
  103. George S. Abrahamse H. Redox potential of antioxidants in cancer progression and prevention. Antioxidants 2020 9 11 1156 10.3390/antiox9111156 33233630
    [Google Scholar]
  104. Qu L. Liu C. Ke C. Zhan X. Li L. Xu H. Xu K. Liu Y. Atractylodes lancea rhizoma attenuates DSS-induced colitis by regulating intestinal flora and metabolites. Am. J. Chin. Med. 2022 50 2 525 552 10.1142/S0192415X22500203 35114907
    [Google Scholar]
  105. Qu L. Shi K. Xu J. Liu C. Ke C. Zhan X. Xu K. Liu Y. Atractylenolide-1 targets SPHK1 and B4GALT2 to regulate intestinal metabolism and flora composition to improve inflammation in mice with colitis. Phytomedicine 2022 98 153945 10.1016/j.phymed.2022.153945 35114452
    [Google Scholar]
  106. Wang Z. Li L. Wang S. Wei J. Qu L. Pan L. Xu K. The role of the gut microbiota and probiotics associated with microbial metabolisms in cancer prevention and therapy. Front. Pharmacol. 2022 13 1025860 10.3389/fphar.2022.1025860 36452234
    [Google Scholar]
  107. Meng D.F. Guo L.L. Peng L.X. Zheng L.S. Xie P. Mei Y. Li C.Z. Peng X.S. Lang Y.H. Liu Z.J. Wang M.D. Xie D.H. Shu D.T. Hu H. Lin S.T. Li H.F. Luo F.F. Sun R. Huang B.J. Qian C.N. Antioxidants suppress radiation-induced apoptosis via inhibiting MAPK pathway in nasopharyngeal carcinoma cells. Biochem. Biophys. Res. Commun. 2020 527 3 770 777 10.1016/j.bbrc.2020.04.093 32446561
    [Google Scholar]
  108. Pan L. Feng F. Wu J. Li L. Xu H. Yang L. Xu K. Wang C. Diosmetin inhibits cell growth and proliferation by regulating the cell cycle and lipid metabolism pathway in hepatocellular carcinoma. Food Funct. 2021 12 23 12036 12046 10.1039/D1FO02111G 34755740
    [Google Scholar]
  109. Hu A. Qiu R. Li W.B. Radical recombination and antioxidants: A hypothesis on the FLASH effect mechanism. Int. J. Radiat. Biol. 2022 99 4 620 628 35938944
    [Google Scholar]
  110. Kim D. Illeperuma R.P. Kim J. The protective effect of antioxidants in areca nut extract-induced oral carcinogenesis. Asian Pac. J. Cancer Prev. 2020 21 8 2447 2452 10.31557/APJCP.2020.21.8.2447 32856877
    [Google Scholar]
  111. Wang H. Wang Q. Dong J. Jiang W. Kong L. Zhang Q. Liu H. New perspective of ceria nanodots for precise tumor therapy via oxidative stress pathway. Heliyon 2022 8 8 e10370 10.1016/j.heliyon.2022.e10370 36061010
    [Google Scholar]
  112. Petri A. Alexandratou E. Yova D. Assessment of natural antioxidants’ effect on PDT cytotoxicity through fluorescence microscopy image analysis. Lasers Surg. Med. 2022 54 2 311 319 10.1002/lsm.23469 34431540
    [Google Scholar]
  113. Shin H.J. Han J.M. Choi Y.S. Jung H.J. Pterostilbene suppresses both cancer cells and cancer stem-like cells in cervical cancer with superior bioavailability to resveratrol. Molecules 2020 25 1 228 10.3390/molecules25010228 31935877
    [Google Scholar]
  114. Li G. Fang S. Shao X. Li Y. Tong Q. Kong B. Chen L. Wang Y. Yang J. Yu H. Xie X. Zhang J. Curcumin reverses NNMT-induced 5-fluorouracil resistance via increasing ROS and cell cycle arrest in colorectal cancer cells. Biomolecules 2021 11 9 1295 10.3390/biom11091295 34572508
    [Google Scholar]
  115. Man Q. Deng Y. Li P. Ma J. Yang Z. Yang X. Zhou Y. Yan X. Licorice ameliorates cisplatin-induced hepatotoxicity through antiapoptosis, antioxidative stress, anti-inflammation, and acceleration of metabolism. Front. Pharmacol. 2020 11 563750 10.3389/fphar.2020.563750 33240085
    [Google Scholar]
  116. Kang D.Y. Sp N. Jang K.J. Jo E.S. Bae S.W. Yang Y.M. Antitumor effects of natural bioactive ursolic acid in embryonic cancer stem cells. J. Oncol. 2022 2022 1 10 10.1155/2022/6737248 35222644
    [Google Scholar]
  117. Fu M. Liu Y. Cheng H. Xu K. Wang G. Coptis chinensis and dried ginger herb combination inhibits gastric tumor growth by interfering with glucose metabolism via LDHA and SLC2A1. J. Ethnopharmacol. 2022 284 114771 10.1016/j.jep.2021.114771 34737010
    [Google Scholar]
  118. Zhang X. Hu B. Sun Y.F. Huang X.W. Cheng J.W. Huang A. Zeng H.Y. Qiu S.J. Cao Y. Fan J. Zhou J. Yang X.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. 2021 11 2 e335 10.1002/ctm2.335 33634982
    [Google Scholar]
  119. Xu H. Li L. Qu L. 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. 2023 37 3 820 833 36420870
    [Google Scholar]
  120. Ghufran H. Azam M. Mehmood A. Ashfaq R. Baig M.T. Malik K. Shahid A.A. Riazuddin S. Tumoricidal effects of unprimed and curcumin-primed adipose-derived stem cells on human hepatoma HepG2 cells under oxidative conditions. Tissue Cell 2022 79 101968 10.1016/j.tice.2022.101968 36356560
    [Google Scholar]
  121. Li H. He M. Zhao P. Liu P. Chen W. Xu X. 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. 2022 2022 1 10 10.1155/2022/4000733 35761835
    [Google Scholar]
  122. Alam M.A. Anti-hypertensive effect of cereal antioxidant ferulic acid and its mechanism of action. Front. Nutr. 2019 6 121 10.3389/fnut.2019.00121 31448280
    [Google Scholar]
  123. Venugopal K. Rather H.A. Rajagopal K. Shanthi M.P. Sheriff K. Illiyas M. Rather R.A. Manikandan E. Uvarajan S. Bhaskar M. Maaza M. 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. B 2017 167 282 289 10.1016/j.jphotobiol.2016.12.013 28110253
    [Google Scholar]
  124. Zhao H. Guo J. Chi Q. Fang M. Molecular mechanisms of tanshinone IIA in Hepatocellular carcinoma therapy via WGCNA-based network pharmacology analysis. Biocell 2022 46 5 1245 1259 10.32604/biocell.2022.018117
    [Google Scholar]
  125. Zhu P. Fan Z. Cancer stem cells and tumorigenesis. Biophys. Rep. 2018 4 4 178 188 10.1007/s41048‑018‑0062‑2 30310855
    [Google Scholar]
  126. Leung H.W. Ko C.H. Yue G.G.L. Herr I. Lau C.B.S. The natural agent 4-vinylphenol targets metastasis and stemness features in breast cancer stem-like cells. Cancer Chemother. Pharmacol. 2018 82 2 185 197 10.1007/s00280‑018‑3601‑0 29777274
    [Google Scholar]
  127. Barzegari A. Nouri M. Gueguen V. Saeedi N. Djavid P.G. Omidi Y. Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells. J. Cell. Physiol. 2020 235 7-8 5628 5636 10.1002/jcp.29495 31989645
    [Google Scholar]
  128. Padhy D. Sharma S. Singh S. Andrographolide protect against lipopolysacharides induced vascular endothelium dysfunction by abrogation of oxidative stress and chronic inflammation in Sprague–Dawley rats. J. Biochem. Mol. Toxicol. 2024 38 1 e23632 10.1002/jbt.23632 38229310
    [Google Scholar]
  129. Wang C. Wang S. Wang Z. Han J. Jiang N. Qu L. Xu K. Andrographolide regulates H3 histone lactylation by interfering with p300 to alleviate aortic valve calcification. Br. J. Pharmacol., 2024 bph.16332 10.1111/bph.16332 38378175
    [Google Scholar]
  130. Wang H. Haridas V. Gutterman J.U. Xu Z.X. Natural triterpenoid avicins selectively induce tumor cell death. Commun. Integr. Biol. 2010 3 3 205 208 10.4161/cib.3.3.11492 20714394
    [Google Scholar]
  131. Issa M.E. Berndt S. Carpentier G. Pezzuto J.M. Cuendet M. Bruceantin inhibits multiple myeloma cancer stem cell proliferation. Cancer Biol. Ther. 2016 17 9 966 975 10.1080/15384047.2016.1210737 27434731
    [Google Scholar]
  132. Feng F. Pan L. Wu J. Li L. Xu H. Yang L. Xu K. Wang C. Cepharanthine inhibits hepatocellular carcinoma cell growth and proliferation by regulating amino acid metabolism and suppresses tumorigenesis in vivo. Int. J. Biol. Sci. 2021 17 15 4340 4352 10.7150/ijbs.64675 34803502
    [Google Scholar]
  133. Zhu Z. Pan H. Li Y. Pan W. Evaluation of the synergism mechanism of tamoxifen and docetaxel by nanoparticles. Anticancer. Agents Med. Chem. 2020 19 16 1991 2000 10.2174/1871520619666190702120829 31267877
    [Google Scholar]
  134. Pan L. Feng F. Wu J. Fan S. Han J. Wang S. Yang L. Liu W. Wang C. Xu K. Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells. Pharmacol. Res. 2022 181 106270 10.1016/j.phrs.2022.106270 35605812
    [Google Scholar]
  135. Wang H. Liu X. Long M. Huang Y. Zhang L. Zhang R. Zheng Y. Liao X. Wang Y. Liao Q. Li W. Tang Z. Tong Q. Wang X. Fang F. de la Vega M.R. Ouyang Q. Zhang D.D. Yu S. Zheng H. NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis. Sci. Transl. Med. 2016 8 334 334ra51 10.1126/scitranslmed.aad6095 27075625
    [Google Scholar]
  136. Xu H. Li L. Wang S. Wang Z. Qu L. Wang C. Xu K. Royal jelly acid suppresses hepatocellular carcinoma tumorigenicity by inhibiting H3 histone lactylation at H3K9la and H3K14la sites. Phytomedicine 2023 118 154940 10.1016/j.phymed.2023.154940 37453194
    [Google Scholar]
  137. Manogaran P. Somasundaram B. Viswanadha V.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. 2022 36 3 e22967 10.1002/jbt.22967 34921482
    [Google Scholar]
  138. Liu S. Wang J. Shao T. Song P. Kong Q. Hua H. Luo T. Jiang Y. The natural agent rhein induces β‐catenin degradation and tumour growth arrest. J. Cell. Mol. Med. 2018 22 1 589 599 10.1111/jcmm.13346 29024409
    [Google Scholar]
  139. Li L. Xu H. Qu L. Nisar M. Farrukh Nisar M. Liu X. Xu K. Water extracts of Polygonum Multiflorum Thunb. and its active component emodin relieves osteoarthritis by regulating cholesterol metabolism and suppressing chondrocyte inflammation. Acupunct. Herb. Med. 2023 3 2 96 106 10.1097/HM9.0000000000000061
    [Google Scholar]
  140. Semwal R.B. Semwal D.K. Combrinck S. Viljoen A. Emodin - A natural anthraquinone derivative with diverse pharmacological activities. Phytochemistry 2021 190 112854 10.1016/j.phytochem.2021.112854 34311280
    [Google Scholar]
  141. Arafa E.S.A. Hassanein E.H.M. Ibrahim N.A. Buabeid M.A. Mohamed W.R. Involvement of Nrf2-PPAR-γ signaling in Coenzyme Q10 protecting effect against methotrexate-induced testicular oxidative damage. Int. Immunopharmacol. 2024 129 111566 10.1016/j.intimp.2024.111566 38364740
    [Google Scholar]
  142. Celik A. Ates B.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. 2023 40 8 244 10.1007/s12032‑023‑02113‑7 37453954
    [Google Scholar]
/content/journals/cad/10.2174/0115734099299174240522115944
Loading
/content/journals/cad/10.2174/0115734099299174240522115944
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test