Skip to content
2000
image of Triptonide Mediates Apoptosis and Autophagy via ROS/p38 MAPK Activation and mTOR/NF-κB Inhibition in Nasopharyngeal Carcinoma: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation

Abstract

Introduction

Despite significant advances in the comprehensive treatment of nasopharyngeal carcinoma (NPC), local recurrence or distant metastasis still occurs in a considerable proportion of patients, leading to poor outcomes and posing a significant clinical challenge. The current therapeutic agent, Triptonide (TN), has shown potential efficacy in modulating cellular autophagy, suggesting its therapeutic promise for treating NPC. However, the precise molecular targets and mechanisms underlying TN’s role in NPC remain to be elucidated.

Methods

Initially, relevant targets for TN in the treatment of NPC were identified through public databases. Next, network pharmacology and bioinformatics analyses were employed to pinpoint the top 15 hub targets and critical signaling pathways involved in TN’s therapeutic action. Finally, experimental validation, including a range of molecular assays, was conducted to investigate the cellular effects of TN treatment, such as apoptosis induction, migration inhibition, Caspase-3 activation, mitochondrial dysfunction, autophagy-related gene expression, and TFAM level detection, thereby confirming the essential genes and pathways.

Results

A total of 31 potential molecular targets for TN in NPC were identified, with 27 genes confirmed through autophagy-related gene analysis. Among these, the top 15 hub genes included RELA, CASP8, NFKBIA, PPARG, PTGS2, MAPK14, MAPK8, HDAC1, ERBB2, CASP1, TERT, AR, CDK1, PGR, and HDAC6. TN was found to activate the MAPK signaling pathway. , TN induced NPC cell apoptosis increased ROS, MAPK14 activation, and Caspase-3 cleavage. It disrupted mitochondrial function (reduced membrane potential, decreased copy number, enhanced fission), inhibited mTOR and RELA phosphorylation, and promoted autophagy. TN also caused S-phase arrest, reduced CDH3, and increased CDH1. Lipoic acid partially reversed TN-induced cytotoxicity.

Discussion

TN exerts anti-NPC effects primarily through MAPK pathway activation and autophagy induction. Key targets mediating these effects include RELA, CASP8, PPARG, MAPK14, MAPK8, HDAC1, ERBB2, and CASP1. The reversal by lipoic acid implicates ROS in TN's mechanism. The disruption of mitochondrial function represents a critical facet of its action.

Conclusion

TN demonstrates potential as a therapeutic agent for NPC, primarily through activation of the MAPK signaling pathway and autophagy. Key targets, including RELA, CASP8, PPARG, MAPK14, MAPK8, HDAC1, ERBB2, and CASP1, have been identified as critical mediators of TN’s effects, highlighting its role in promoting autophagy and enhancing NPC treatment.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128392691251008235211
2025-10-31
2026-01-27

  • From This Site

    /content/journals/cpd/10.2174/0113816128392691251008235211
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Chen Y.P. Chan A.T.C. Le Q.T. Blanchard P. Sun Y. Ma J. Nasopharyngeal carcinoma. Lancet 2019 394 10192 64 80 10.1016/S0140‑6736(19)30956‑0 31178151
    [Google Scholar]
  2. Tang L.L. Chen Y.P. Chen C.B. The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma. Cancer Commun. (Lond.) 2021 41 11 1195 1227 10.1002/cac2.12218 34699681
    [Google Scholar]
  3. Hu J. Huang Q. Gao J. Mixed photon and carbon-ion beam radiotherapy in the management of non-metastatic nasopharyngeal carcinoma. Front. Oncol. 2021 11 653050 10.3389/fonc.2021.653050 34367954
    [Google Scholar]
  4. Fang X. Sun P. Dong Y. Huang Y. Lu J.J. Kong L. In vitro evaluation of photon and carbon ion radiotherapy in combination with cisplatin in head and neck squamous cell carcinoma cell lines. Front. Oncol. 2023 13 896142 10.3389/fonc.2023.896142 37081974
    [Google Scholar]
  5. Lee N.Y. Harris J. Kim J. Long-term outcomes of bevacizumab and chemoradiation for locoregionally advanced nasopharyngeal carcinoma. JAMA Netw. Open 2023 6 6 e2316094 10.1001/jamanetworkopen.2023.16094 37266942
    [Google Scholar]
  6. Ng J.P.Z. Lam W.Y.H. Pow E.H.N. Botelho M.G. A qualitative analysis of patient’s lived experience on their treatment journey with nasopharyngeal carcinoma. J. Dent. 2023 134 104518 10.1016/j.jdent.2023.104518 37088259
    [Google Scholar]
  7. Kocaturk N.M. Akkoc Y. Kig C. Bayraktar O. Gozuacik D. Kutlu O. Autophagy as a molecular target for cancer treatment. Eur. J. Pharm. Sci. 2019 134 116 137 10.1016/j.ejps.2019.04.011 30981885
    [Google Scholar]
  8. Debnath J. Gammoh N. Ryan K.M. Autophagy and autophagy-related pathways in cancer. Nat. Rev. Mol. Cell Biol. 2023 24 8 560 575 10.1038/s41580‑023‑00585‑z 36864290
    [Google Scholar]
  9. Fernando W. Rupasinghe H.P.V. Hoskin D.W. Dietary phytochemicals with anti-oxidant and pro-oxidant activities: A double-edged sword in relation to adjuvant chemotherapy and radiotherapy? Cancer Lett. 2019 452 168 177 10.1016/j.canlet.2019.03.022 30910593
    [Google Scholar]
  10. Srinivas U.S. Tan B.W.Q. Vellayappan B.A. Jeyasekharan A.D. ROS and the DNA damage response in cancer. Redox Biol. 2019 25 101084 10.1016/j.redox.2018.101084 30612957
    [Google Scholar]
  11. Filomeni G. De Zio D. Cecconi F. Oxidative stress and autophagy: The clash between damage and metabolic needs. Cell Death Differ. 2015 22 3 377 388 10.1038/cdd.2014.150 25257172
    [Google Scholar]
  12. Wang B. Wang Y. Zhang J. ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis. Arch. Toxicol. 2023 97 6 1439 1451 10.1007/s00204‑023‑03476‑6 37127681
    [Google Scholar]
  13. Chen H.T. Liu H. Mao M.J. Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy. Mol. Cancer 2019 18 1 101 10.1186/s12943‑019‑1030‑2 31126310
    [Google Scholar]
  14. Averbeck D. Rodriguez-Lafrasse C. Role of mitochondria in radiation responses: Epigenetic, metabolic, and signaling impacts. Int. J. Mol. Sci. 2021 22 20 11047 10.3390/ijms222011047 34681703
    [Google Scholar]
  15. Porporato P.E. Filigheddu N. Pedro J.M.B.S. Kroemer G. Galluzzi L. Mitochondrial metabolism and cancer. Cell Res. 2018 28 3 265 280 10.1038/cr.2017.155 29219147
    [Google Scholar]
  16. Zhou B.N. Some progress on the chemistry of natural bioactive terpenoids form Chinese medicinal plants. Mem. Inst. Oswaldo Cruz 1991 86 219 226 10.1590/S0074‑02761991000600049 1842005
    [Google Scholar]
  17. Song J. He G.N. Dai L. A comprehensive review on celastrol, triptolide and triptonide: Insights on their pharmacological activity, toxicity, combination therapy, new dosage form and novel drug delivery routes. Biomed. Pharmacother. 2023 162 114705 10.1016/j.biopha.2023.114705 37062220
    [Google Scholar]
  18. Zhang M. Meng M. Liu Y. Triptonide effectively inhibits triple-negative breast cancer metastasis through concurrent degradation of Twist1 and Notch1 oncoproteins. Breast Cancer Res. 2021 23 1 116 10.1186/s13058‑021‑01488‑7 34922602
    [Google Scholar]
  19. Zhou L. Peng S. Chen X.L. Triptonide inhibits the cervical cancer cell growth via downregulating the RTKs and inactivating the Akt-mTOR pathway. Oxid. Med. Cell. Longev. 2022 2022 1 20 10.1155/2022/8550817 39282148
    [Google Scholar]
  20. Zhang H. Mao Y. Zou X. Triptonide inhibits growth and metastasis in HCC by suppressing EGFR/PI3K/AKT signaling. Neoplasma 2023 70 1 94 102 10.4149/neo_2022_221118N1112 36637084
    [Google Scholar]
  21. Zhang B. Meng M. Xiang S. Selective activation of tumor-suppressive MAPKP signaling pathway by triptonide effectively inhibits pancreatic cancer cell tumorigenicity and tumor growth. Biochem. Pharmacol. 2019 166 70 81 10.1016/j.bcp.2019.05.010 31075266
    [Google Scholar]
  22. Chinison J. Aguilar J.S. Avalos A. Triptonide effectively inhibits Wnt/β-catenin signaling via c-terminal transactivation domain of β-catenin. Sci. Rep. 2016 6 1 32779 10.1038/srep32779 27596363
    [Google Scholar]
  23. Geng S. Chen L. Lin W. Exploring the therapeutic potential of triptonide in salivary adenoid cystic carcinoma: A comprehensive approach involving network pharmacology and experimental validation. Curr. Pharm. Des. 2024 30 29 2276 2289 10.2174/0113816128315277240610052453 38910414
    [Google Scholar]
  24. Kim S. Chen J. Cheng T. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 2021 49 D1 D1388 D1395 10.1093/nar/gkaa971 33151290
    [Google Scholar]
  25. Daina A. Michielin O. Zoete V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019 47 W1 W357-64 10.1093/nar/gkz382 31106366
    [Google Scholar]
  26. Wang X. Shen Y. Wang S. PharmMapper 2017 update: A web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res. 2017 45 W1 W356-60 10.1093/nar/gkx374 28472422
    [Google Scholar]
  27. Safran M. Dalah I. Alexander J. GeneCards Version 3: The human gene integrator. Database (Oxford) 2010 2010 0 baq020 10.1093/database/baq020 20689021
    [Google Scholar]
  28. Piñero J. Bravo À. Queralt-Rosinach N. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 2017 45 D1 D833 D839 10.1093/nar/gkw943 27924018
    [Google Scholar]
  29. Li J. Tao Q. Xie Y. Exploring the targets and molecular mechanisms of thalidomide in the treatment of ulcerative colitis: Network pharmacology and experimental validation. Curr. Pharm. Des. 2023 29 34 2721 2737 10.2174/0113816128272502231101114727 37961863
    [Google Scholar]
  30. Szklarczyk D. Kirsch R. Koutrouli M. The STRING database in 2023: Protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023 51 D1 D638 D646 10.1093/nar/gkac1000 36370105
    [Google Scholar]
  31. Shannon P. Markiel A. Ozier O. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 13 11 2498 2504 10.1101/gr.1239303 14597658
    [Google Scholar]
  32. Chin C.H. Chen S.H. Wu H.H. Ho C.W. Ko M.T. Lin C.Y. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol. 2014 8 S4 S11 10.1186/1752‑0509‑8‑S4‑S11 25521941
    [Google Scholar]
  33. Yu G. Wang L.G. Han Y. He Q.Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012 16 5 284 287 10.1089/omi.2011.0118 22455463
    [Google Scholar]
  34. Berman H.M. Westbrook J. Feng Z. The protein data bank. Nucleic Acids Res. 2000 28 1 235 242 10.1093/nar/28.1.235 10592235
    [Google Scholar]
  35. Morris G.M. Huey R. Lindstrom W. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009 30 16 2785 2791 10.1002/jcc.21256 19399780
    [Google Scholar]
  36. Seeliger D. de Groot B.L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J. Comput. Aided Mol. Des. 2010 24 5 417 422 10.1007/s10822‑010‑9352‑6 20401516
    [Google Scholar]
  37. Du W. Wang L. Liao Z. Wang J. Circ_0085289 alleviates the progression of periodontitis by regulating let-7f-5p/SOCS6 Pathway. Inflammation 2021 44 4 1607 1619 10.1007/s10753‑021‑01445‑8 33710445
    [Google Scholar]
  38. Cho S. Hong S.J. Kang S.H. Park Y. Kim S.K. Alpha-lipoic acid attenuates apoptosis and ferroptosis in cisplatin-induced ototoxicity via the reduction of intracellular lipid droplets. Int. J. Mol. Sci. 2022 23 18 10981 10.3390/ijms231810981 36142894
    [Google Scholar]
  39. Heywood H.K. Lee D.A. Bioenergetic reprogramming of articular chondrocytes by exposure to exogenous and endogenous reactive oxygen species and its role in the anabolic response to low oxygen. J. Tissue Eng. Regen. Med. 2017 11 8 2286 2294 10.1002/term.2126 26799635
    [Google Scholar]
  40. Sun R. Zhang P.P. Weng X.Q. Therapeutic targeting miR130b counteracts diffuse large B-cell lymphoma progression via OX40/OX40L-mediated interaction with Th17 cells. Signal Transduct. Target. Ther. 2022 7 1 80 10.1038/s41392‑022‑00895‑2 35301282
    [Google Scholar]
  41. Liu Y. Teng L. Lyu Y. Song G. Zhang X.B. Tan W. Ratiometric afterglow luminescent nanoplatform enables reliable quantification and molecular imaging. Nat. Commun. 2022 13 1 2216 10.1038/s41467‑022‑29894‑1 35468901
    [Google Scholar]
  42. Ekstrand M.I. Falkenberg M. Rantanen A. Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum. Mol. Genet. 2004 13 9 935 944 10.1093/hmg/ddh109 15016765
    [Google Scholar]
  43. Kang D. Kim S.H. Hamasaki N. Mitochondrial transcription factor A (TFAM): Roles in maintenance of mtDNA and cellular functions. Mitochondrion 2007 7 1-2 39 44 10.1016/j.mito.2006.11.017 17280879
    [Google Scholar]
  44. Chen A. Kristiansen C.K. Høyland L.E. POLG mutations lead to abnormal mitochondrial remodeling during neural differentiation of human pluripotent stem cells via SIRT3/AMPK pathway inhibition. Cell Cycle 2022 21 11 1178 1193 10.1080/15384101.2022.2044136 35298342
    [Google Scholar]
  45. Lou R. Yang T. Zhang X. Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy. Bioorg. Med. Chem. 2024 110 117788 10.1016/j.bmc.2024.117788 38964974
    [Google Scholar]
  46. Zhou Y. Chi Y. Bhandari A. Downregulated CDH3 decreases proliferation, migration, and invasion in thyroid cancer. Am. J. Transl. Res. 2020 12 6 3057 3067 [PMID: 32655830
    [Google Scholar]
  47. Hwang P.Y. Mathur J. Cao Y. A Cdh3-β-catenin-laminin signaling axis in a subset of breast tumor leader cells control leader cell polarization and directional collective migration. Dev. Cell 2023 58 1 34 50.e9 10.1016/j.devcel.2022.12.005 36626870
    [Google Scholar]
  48. Ahmed A. Tait S.W.G. Targeting immunogenic cell death in cancer. Mol. Oncol. 2020 14 12 2994 3006 10.1002/1878‑0261.12851 33179413
    [Google Scholar]
  49. Yi M. Zheng X. Niu M. Zhu S. Ge H. Wu K. Combination strategies with PD-1/PD-L1 blockade: Current advances and future directions. Mol. Cancer 2022 21 1 28 10.1186/s12943‑021‑01489‑2 35062949
    [Google Scholar]
  50. Perelman A. Wachtel C. Cohen M. Haupt S. Shapiro H. Tzur A. JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis. 2012 3 11 e430 10.1038/cddis.2012.171 23171850
    [Google Scholar]
  51. Marcondes N.A. Terra S.R. Lasta C.S. Comparison of JC‐1 and MitoTracker probes for mitochondrial viability assessment in stored canine platelet concentrates: A flow cytometry study. Cytometry A 2019 95 2 214 218 10.1002/cyto.a.23567 30107098
    [Google Scholar]
  52. Liu X. Zhao P. Wang X. Celastrol mediates autophagy and apoptosis via the ROS/JNK and Akt/mTOR signaling pathways in glioma cells. J. Exp. Clin. Cancer Res. 2019 38 1 184 10.1186/s13046‑019‑1173‑4 31053160
    [Google Scholar]
  53. Lin W. Chen L. Zhang H. Tumor-intrinsic YTHDF1 drives immune evasion and resistance to immune checkpoint inhibitors via promoting MHC-I degradation. Nat. Commun. 2023 14 1 265 10.1038/s41467‑022‑35710‑7 36650153
    [Google Scholar]
  54. Lin X.H. Qiu B.Q. Ma M. Suppressing DRP1-mediated mitochondrial fission and mitophagy increases mitochondrial apoptosis of hepatocellular carcinoma cells in the setting of hypoxia. Oncogenesis 2020 9 7 67 10.1038/s41389‑020‑00251‑5 32661251
    [Google Scholar]
  55. Dunlop E.A. Tee A.R. mTOR and autophagy: A dynamic relationship governed by nutrients and energy. Semin. Cell Dev. Biol. 2014 36 121 129 10.1016/j.semcdb.2014.08.006 25158238
    [Google Scholar]
  56. Zhang Y. Rumgay H. Li M. Cao S. Chen W. Nasopharyngeal cancer incidence and mortality in 185 Countries in 2020 and the Projected Burden in 2040: Population-based global epidemiological profiling. JMIR Public Health Surveill. 2023 9 e49968 10.2196/49968 37728964
    [Google Scholar]
  57. Wu S. Quan R. Han L. Analysis of intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma. Medicine (Baltimore) 2020 99 30 e21325 10.1097/MD.0000000000021325 32791728
    [Google Scholar]
  58. Ng W.T. Wong E.C.Y. Cheung A.K.W. Patterns of care and treatment outcomes for local recurrence of NPC after definite IMRT—A study by the HKNPCSG. Head Neck 2019 41 10 3661 3669 10.1002/hed.25892 31350940
    [Google Scholar]
  59. Zhao Y. Ma Y. Zang A. First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors. J. Hematol. Oncol. 2023 16 1 50 10.1186/s13045‑023‑01445‑1 37158938
    [Google Scholar]
  60. Wang F.H. Wei X.L. Feng J. Efficacy, safety, and correlative biomarkers of Toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: A phase ii clinical trial (POLARIS-02). J. Clin. Oncol. 2021 39 7 704 712 10.1200/JCO.20.02712 33492986
    [Google Scholar]
  61. Tang L.L. Guo R. Zhang N. Effect of radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy on survival without disease relapse in patients with low-risk nasopharyngeal carcinoma. JAMA 2022 328 8 728 736 10.1001/jama.2022.13997 35997729
    [Google Scholar]
  62. Dong F. Yang P. Wang R. Triptonide acts as a novel antiprostate cancer agent mainly through inhibition of mTOR signaling pathway. Prostate 2019 79 11 1284 1293 10.1002/pros.23834 31212374
    [Google Scholar]
  63. Wang S. Lv Y. Xu X.C. Triptonide inhibits human nasopharyngeal carcinoma cell growth via disrupting Lnc-RNA THOR-IGF2BP1 signaling. Cancer Lett. 2019 443 13 24 10.1016/j.canlet.2018.11.028 30503558
    [Google Scholar]
  64. Xu Y. Wang P. Li M. Natural small molecule triptonide inhibits lethal acute myeloid leukemia with FLT3-ITD mutation by targeting Hedgehog/FLT3 signaling. Biomed. Pharmacother. 2021 133 111054 10.1016/j.biopha.2020.111054 33254022
    [Google Scholar]
  65. Liu Y. Ruan X. Li J. The Osteocyte Stimulated by Wnt Agonist SKL2001 Is a Safe Osteogenic Niche Improving Bioactivities in a Polycaprolactone and Cell Integrated 3D Module. Cells 2022 11 5 831 10.3390/cells11050831 35269452
    [Google Scholar]
  66. Bhattarai K.R. Riaz T.A. Kim H.R. Chae H.J. The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling. Exp. Mol. Med. 2021 53 2 151 167 10.1038/s12276‑021‑00560‑8 33558590
    [Google Scholar]
  67. Zhao M. Wang Y. Li L. Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance. Theranostics 2021 11 4 1845 1863 10.7150/thno.50905 33408785
    [Google Scholar]
  68. Zhang L. Wang L. Fang Y. Phosphorylated transcription factor PuHB40 mediates ROS-dependent anthocyanin biosynthesis in pear exposed to high light. Plant Cell 2024 36 9 3562 3583 10.1093/plcell/koae167 38842382
    [Google Scholar]
  69. Afanas’ev I. New nucleophilic mechanisms of ros-dependent epigenetic modifications: comparison of aging and cancer. Aging Dis. 2013 5 1 52 62 [PMID: 24490117
    [Google Scholar]
  70. Chen X. Li J. Kang R. Klionsky D.J. Tang D. Ferroptosis: Machinery and regulation. Autophagy 2021 17 9 2054 2081 10.1080/15548627.2020.1810918 32804006
    [Google Scholar]
  71. Ren Y. Wang R. Weng S. Multifaceted role of redox pattern in the tumor immune microenvironment regarding autophagy and apoptosis. Mol. Cancer 2023 22 1 130 10.1186/s12943‑023‑01831‑w 37563639
    [Google Scholar]
  72. Wei Y. Jia S. Ding Y. Xia S. Giunta S. Balanced basal-levels of ROS (redox-biology), and very-low-levels of pro-inflammatory cytokines (cold-inflammaging), as signaling molecules can prevent or slow-down overt-inflammaging, and the aging-associated decline of adaptive-homeostasis. Exp. Gerontol. 2023 172 112067 10.1016/j.exger.2022.112067 36535453
    [Google Scholar]
  73. Wang Z. Gong X. Li J. Oxygen-delivering polyfluorocarbon nanovehicles improve tumor oxygenation and potentiate photodynamic-mediated antitumor immunity. ACS Nano 2021 15 3 5405 5419 10.1021/acsnano.1c00033 33625842
    [Google Scholar]
  74. Zheng W.Q. Zhang J.H. Li Z.H. Mammalian mitochondrial translation infidelity leads to oxidative stress–induced cell cycle arrest and cardiomyopathy. Proc. Natl. Acad. Sci. USA 2023 120 37 e2309714120 10.1073/pnas.2309714120 37669377
    [Google Scholar]
  75. Yu F. Wei J. Cui X. Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response. Nucleic Acids Res. 2021 49 10 5779 5797 10.1093/nar/gkab415 34048572
    [Google Scholar]
  76. Mazat J.P. Devin A. Ransac S. Modelling mitochondrial ROS production by the respiratory chain. Cell. Mol. Life Sci. 2020 77 3 455 465 10.1007/s00018‑019‑03381‑1 31748915
    [Google Scholar]
  77. Correia-Álvarez E Keating JE Glish G Tarran R Sassano MF Reactive oxygen species, mitochondrial membrane potential, and cellular membrane potential are predictors of E-Liquid Induced Cellular Toxicity. Nicotine Tob Res 2020 22 S4-S13.(Suppl. 1) 10.1093/ntr/ntaa177 33320253
    [Google Scholar]
  78. Li Z. Han Y. Ji Y. Sun K. Chen Y. Hu K. The effect of a-Lipoic acid (ALA) on oxidative stress, inflammation, and apoptosis in high glucose–induced human corneal epithelial cells. Graefes Arch. Clin. Exp. Ophthalmol. 2023 261 3 735 748 10.1007/s00417‑022‑05784‑6 36058948
    [Google Scholar]
  79. Long S. Zheng Y. Deng X. Maintaining mitochondrial DNA copy number mitigates ROS-induced oocyte decline and female reproductive aging. Commun. Biol. 2024 7 1 1229 10.1038/s42003‑024‑06888‑x 39354016
    [Google Scholar]
  80. Pan Y. Meng M. Zheng N. Targeting of multiple senescence-promoting genes and signaling pathways by triptonide induces complete senescence of acute myeloid leukemia cells. Biochem. Pharmacol. 2017 126 34 50 10.1016/j.bcp.2016.11.024 27908660
    [Google Scholar]
  81. Sahoo G. Samal D. Khandayataray P. Murthy M.K. A review on caspases: Key regulators of biological activities and apoptosis. Mol. Neurobiol. 2023 60 10 5805 5837 10.1007/s12035‑023‑03433‑5 37349620
    [Google Scholar]
  82. Yang S. Li F. Lu S. Ginseng root extract attenuates inflammation by inhibiting the MAPK/NF-κB signaling pathway and activating autophagy and p62-Nrf2-Keap1 signaling in vitro and in vivo. J. Ethnopharmacol. 2022 283 114739 10.1016/j.jep.2021.114739 34648903
    [Google Scholar]
  83. Shen T. Miao Y. Ding C. Activation of the p38/MAPK pathway regulates autophagy in response to the CYPOR-dependent oxidative stress induced by zearalenone in porcine intestinal epithelial cells. Food Chem. Toxicol. 2019 131 110527 10.1016/j.fct.2019.05.035 31173817
    [Google Scholar]
  84. Liu Z. Sin K.W.T. Ding H. p38β MAPK mediates ULK1-dependent induction of autophagy in skeletal muscle of tumor-bearing mice. Cell Stress 2018 2 11 311 324 10.15698/cst2018.11.163 31225455
    [Google Scholar]
  85. Miller D.R. Thorburn A. Autophagy and organelle homeostasis in cancer. Dev. Cell 2021 56 7 906 918 10.1016/j.devcel.2021.02.010 33689692
    [Google Scholar]
  86. Zhang X. Cheng X. Yu L. MCOLN1 is a ROS sensor in lysosomes that regulates autophagy. Nat. Commun. 2016 7 1 12109 10.1038/ncomms12109 27357649
    [Google Scholar]
  87. Vieira A.F. Paredes J. P-cadherin and the journey to cancer metastasis. Mol. Cancer 2015 14 1 178 10.1186/s12943‑015‑0448‑4 26438065
    [Google Scholar]
  88. Fucikova J. Spisek R. Kroemer G. Galluzzi L. Calreticulin and cancer. Cell Res. 2021 31 1 5 16 10.1038/s41422‑020‑0383‑9 32733014
    [Google Scholar]
  89. Hsu C. Lee S.H. Ejadi S. Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1–positive nasopharyngeal carcinoma: Results of the KEYNOTE-028 Study. J. Clin. Oncol. 2017 35 36 4050 4056 10.1200/JCO.2017.73.3675 28837405
    [Google Scholar]
  90. Hu D.D. Chen X.L. Xiao X.R. Comparative metabolism of tripolide and triptonide using metabolomics. Food Chem. Toxicol. 2018 115 98 108 10.1016/j.fct.2018.03.009 29534979
    [Google Scholar]
  91. Yao J. Zhang L. Zhao X. Hu L. Jiang Z. Simultaneous determination of triptolide, wilforlide A and triptonide in human plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry. Biol. Pharm. Bull. 2006 29 7 1483 1486 10.1248/bpb.29.1483 16819194
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128392691251008235211
Loading
Triptonide Mediates Apoptosis and Autophagy via ROS/p38 MAPK Activation and mTOR/NF-κB Inhibition in Nasopharyngeal Carcinoma: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation
Bentham Science Publishers ; https://doi.org/10.2174/0113816128392691251008235211
/content/journals/cpd/10.2174/0113816128392691251008235211
/content/journals/cpd/10.2174/0113816128392691251008235211
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: nasopharyngeal carcinoma ; network pharmacology ; mitochondrial dysfunction ; Triptonide ; MAPK signaling pathway ; autophagy

Most Cited Most Cited RSS feed

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