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image of Exploring the Mechanism of Centipeda minima in Treating Nasopharyngeal Carcinoma Based on Network Pharmacology

Abstract

Background

Centipeda minima (CM) is a traditional Chinese herbal medicine used for the treatment of sinusitis and rhinitis, and it possesses anti-cancer properties. However, the mechanism of CM in the treatment of nasopharyngeal carcinoma (NPC) remains unclear.

Objective

This study aimed to explore the mechanism of CM in the treatment of NPC using a network pharmacology approach.

Methods

The active components and targets of CM and NPC were screened using TCMSP, SwissTarget, and GeneCards database. The association between CM components and NPC targets or pathways was analyzed using String, Cytoscape 3.9.1, David 6.7, and AutoDock Vina. The Sangerbox platform was used to conduct differential expression and Kaplan-Meier survival analysis of core genes.

Results

We identified 17 active compounds of CM and 146 corresponding targeted proteins in NPC. These targets may modulate pathways in cancer, PI3K-Akt, apoptosis, prolactin, relaxin, and TNF signaling. The top 5 core genes of the PPI network were found to be AKT1, STAT3, CASP3, EGFR, and SRC, which may be the main targets of CM in treating NPC. Molecular docking confirmed the binding energies of quercetin with CASP3, 8-Hydroxy-9,10-diisobutyryloxythymol with AKT1, and plenolin with AKT1, which were particularly low, suggesting robust and stable interactions. The expression levels of AKT1, CASP3, EGFR, SRC, MMP9, CCND1, and PTGS2 were significantly higher in head and neck squamous cell carcinoma (HNSC) samples compared to normal samples. In addition, the hub genes could predict the prognosis of HNSC as the Kaplan-Meier survival curve showed that patients with lower expressions of AKT1, STAT3, CASP3, EGFR, MMP9, ESR1, PTGS2, and PPARG had better overall survival.

Conclusion

By conducting a network pharmacology approach, we revealed the main ingredients, key targets, and regulatory pathways of Centipeda minima in the treatment of NPC.

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2024-10-14
2025-01-18
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References

  1. Ding R.B. Chen P. Rajendran B.K. Lyu X. Wang H. Bao J. Zeng J. Hao W. Sun H. Wong A.H.H. Valecha M.V. Yang E.J. Su S.M. Choi T.K. Liu S. Chan K.I. Yang L.L. Wu J. Miao K. Chen Q. Shim J.S. Xu X. Deng C.X. Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics. Nat. Commun. 2021 12 1 3046 10.1038/s41467‑021‑23379‑3 34031426
    [Google Scholar]
  2. 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]
  3. Guo Z. Li Z. Zhang M. Bao M. He B. Zhou X. LncRNA FAS-AS1 upregulated by its genetic variation rs6586163 promotes cell apoptosis in nasopharyngeal carcinoma through regulating mitochondria function and Fas splicing. Sci. Rep. 2023 13 1 8218 10.1038/s41598‑023‑35502‑z 37217794
    [Google Scholar]
  4. Tang L.L. Chen Y.P. Chen C.B. Chen M.Y. Chen N.Y. Chen X.Z. Du X.J. Fang W.F. Feng M. Gao J. Han F. He X. Hu C.S. Hu D. Hu G.Y. Jiang H. Jiang W. Jin F. Lang J.Y. Li J.G. Lin S.J. Liu X. Liu Q.F. Ma L. Mai H.Q. Qin J.Y. Shen L.F. Sun Y. Wang P.G. Wang R.S. Wang R.Z. Wang X.S. Wang Y. Wu H. Xia Y.F. Xiao S.W. Yang K.Y. Yi J.L. Zhu X.D. Ma J. 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]
  5. Guo Z. Wang Y.J. He B.S. Zhou J. Linc00312 single nucleotide polymorphism as biomarker for chemoradiotherapy induced hematotoxicity in nasopharyngeal carcinoma patients. Dis. Markers 2022 2022 1 9 10.1155/2022/6707821 35990252
    [Google Scholar]
  6. Cheng M. Li T. Hu E. Yan Q. Li H. Wang Y. Luo J. Tang T. A novel strategy of integrating network pharmacology and transcriptome reveals antiapoptotic mechanisms of Buyang Huanwu Decoction in treating intracerebral hemorrhage. J. Ethnopharmacol. 2024 319 Pt 1 117123 10.1016/j.jep.2023.117123 37673200
    [Google Scholar]
  7. Su Y.N. Wang M.J. Yang J.P. Wu X.L. Xia M. Bao M.H. Ding Y.B. Feng Q. Fu L.J. Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome. Front. Endocrinol. (Lausanne) 2023 14 1122709 10.3389/fendo.2023.1122709 36814581
    [Google Scholar]
  8. Dai B. Wu Q. Zeng C. Zhang J. Cao L. Xiao Z. Yang M. The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance. J. Ethnopharmacol. 2016 192 382 389 10.1016/j.jep.2016.07.024 27401286
    [Google Scholar]
  9. He R. He F. Hu Z. He Y. Zeng X. Liu Y. Tang L. Xiang J. Li J. He B. Xiang Q. Analysis of potential mechanism of herbal formula Taohong Siwu decoction against vascular dementia based on network pharmacology and molecular docking. BioMed Res. Int. 2023 2023 1 1235552 10.1155/2023/1235552 36726841
    [Google Scholar]
  10. Zhou J. Li H. Wu B. Zhu L. Huang Q. Guo Z. He Q. Wang L. Peng X. Guo T. Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer. Sci. Rep. 2024 14 1 1860 10.1038/s41598‑024‑52413‑9 38253629
    [Google Scholar]
  11. Wei S. Sun T. Du J. Zhang B. Xiang D. Li W. Xanthohumol, a prenylated flavonoid from Hops, exerts anticancer effects against gastric cancer in vitro. Oncol. Rep. 2018 40 6 3213 3222 10.3892/or.2018.6723 30272303
    [Google Scholar]
  12. Liu Y.Q. Zhou G.B. Promising anticancer activities and mechanisms of action of active compounds from the medicinal herb Centipeda minima (L.) A. Braun & Asch. Phytomedicine 2022 106 154397 10.1016/j.phymed.2022.154397 36084403
    [Google Scholar]
  13. Tan J. Qiao Z. Meng M. Zhang F. Kwan H.Y. Zhong K. Yang C. Wang Y. Zhang M. Liu Z. Su T. Centipeda minima: An update on its phytochemistry, pharmacology and safety. J. Ethnopharmacol. 2022 292 115027 10.1016/j.jep.2022.115027 35091011
    [Google Scholar]
  14. Linh N.T.T. Ha N.T.T. Tra N.T. Anh L.T.T. Tuyen N.V. Son N.T. Medicinal plant Centipeda minima: A resource of bioactive compounds. Mini Rev. Med. Chem. 2021 21 3 273 287 10.2174/1389557520666201021143257 33087028
    [Google Scholar]
  15. Bhati V. Kumar A. Lather V. Sharma R. Pandita D. Association of temozolomide with progressive multifocal leukoencephalopathy: A disproportionality analysis integrated with network pharmacology. Expert Opin. Drug Saf. 2024 23 5 649 658 10.1080/14740338.2023.2278682 37915230
    [Google Scholar]
  16. Saima L.S. Latha S. Sharma R. Kumar A. Role of network pharmacology in prediction of mechanism of neuroprotective compounds. Methods Mol. Biol. 2024 2761 159 179 10.1007/978‑1‑0716‑3662‑6_13 38427237
    [Google Scholar]
  17. Singh R. Kumar A. Lather V. Sharma R. Pandita D. Identification of novel signal of Raynaud’s phenomenon with Calcitonin Gene-Related Peptide(CGRP) antagonists using data mining algorithms and network pharmacological approaches. Expert Opin. Drug Saf. 2024 23 2 231 238 10.1080/14740338.2023.2248877 37594041
    [Google Scholar]
  18. Hu E. Li Z. Li T. Yang X. Ding R. Jiang H. Su H. Cheng M. Yu Z. Li H. Tang T. Wang Y. A novel microbial and hepatic biotransformation-integrated network pharmacology strategy explores the therapeutic mechanisms of bioactive herbal products in neurological diseases: The effects of Astragaloside IV on intracerebral hemorrhage as an example. Chin. Med. 2023 18 1 40 10.1186/s13020‑023‑00745‑5 37069580
    [Google Scholar]
  19. Tiwari P. Ali S.A. Puri B. Kumar A. Datusalia A.K. Tinospora cordifolia Miers enhances the immune response in mice immunized with JEV-vaccine: A network pharmacology and experimental approach. Phytomedicine 2023 119 154976 10.1016/j.phymed.2023.154976 37573808
    [Google Scholar]
  20. Zhao L. Zhang H. Li N. Chen J. Xu H. Wang Y. Liang Q. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J. Ethnopharmacol. 2023 309 116306 10.1016/j.jep.2023.116306 36858276
    [Google Scholar]
  21. Liu J. Zheng W. He Y. Zhang W. Luo Z. Liu X. Jiang X. Meng F. Wu L. A review of the research applications of Centipeda minima. Molecules 2023 29 1 108 10.3390/molecules29010108 38202691
    [Google Scholar]
  22. Jia Y. Zou J. Wang Y. Zhang X. Shi Y. Liang Y. Guo D. Yang M. Mechanism of allergic rhinitis treated by Centipeda minima from different geographic areas. Pharm. Biol. 2021 59 1 604 616 10.1080/13880209.2021.1923757 34010591
    [Google Scholar]
  23. Lee M.M.L. Chan B.D. Wong W.Y. Qu Z. Chan M.S. Leung T.W. Lin Y. Mok D.K.W. Chen S. Tai W.C.S. Anti-cancer activity of Centipeda minima extract in triple negative breast cancer via inhibition of AKT, NF-κB, and STAT3 signaling pathways. Front. Oncol. 2020 10 491 10.3389/fonc.2020.00491 32328465
    [Google Scholar]
  24. Wang M. Guo H. Sun B.B. Jie X.L. Shi X.Y. Liu Y.Q. Shi X.L. Ding L.Q. Xue P.H. Qiu F. Cao W. Wang G.Z. Zhou G.B. Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer. Phytomedicine 2024 132 155825 10.1016/j.phymed.2024.155825 38968790
    [Google Scholar]
  25. Fan X.Z. Chen Y.F. Zhang S.B. He D.H. Wei S.F. Wang Q. Pan H.F. Liu Y.Q. Centipeda minima extract sensitizes lung cancer cells to DNA-crosslinking agents via targeting Fanconi anemia pathway. Phytomedicine 2021 91 153689 10.1016/j.phymed.2021.153689 34446320
    [Google Scholar]
  26. Guo Y. Sun H. Chan C. Liu B. Wu J. Chan S. Mok D.K.W. Tse A.K.W. Yu Z. Chen S. Centipeda minima (Ebushicao) extract inhibits PI3K-Akt-mTOR signaling in nasopharyngeal carcinoma CNE-1 cells. Chin. Med. 2015 10 1 26 10.1186/s13020‑015‑0058‑5 26388933
    [Google Scholar]
  27. Deepika Maurya P.K. Health benefits of quercetin in age-related diseases. Molecules 2022 27 8 2498 10.3390/molecules27082498
    [Google Scholar]
  28. Reyes-Farias M. Carrasco-Pozo C. The anti-cancer effect of quercetin: Molecular implications in cancer metabolism. Int. J. Mol. Sci. 2019 20 13 3177 10.3390/ijms20133177 31261749
    [Google Scholar]
  29. Liu R. Dow Chan B. Mok D.K.W. Lee C.S. Tai W.C.S. Chen S. Arnicolide D, from the herb Centipeda minima, is a therapeutic candidate against nasopharyngeal carcinoma. Molecules 2019 24 10 1908 10.3390/molecules24101908 31108969
    [Google Scholar]
  30. Rauf A. Imran M. Butt M.S. Nadeem M. Peters D.G. Mubarak M.S. Resveratrol as an anti-cancer agent: A review. Crit. Rev. Food Sci. Nutr. 2018 58 9 1428 1447 10.1080/10408398.2016.1263597 28001084
    [Google Scholar]
  31. Su M. Li Y. Chung H.Y. Ye W. 2beta-(Isobutyryloxy)florilenalin, a sesquiterpene lactone isolated from the medicinal plant Centipeda minima, induces apoptosis in human nasopharyngeal carcinoma CNE cells. Molecules 2009 14 6 2135 2146 10.3390/molecules14062135 19553887
    [Google Scholar]
  32. Su M. Wu P. Li Y. Chung H.Y. Antiproliferative effects of volatile oils from Centipeda minima on human nasopharyngeal cancer CNE cells. Nat. Prod. Commun. 2010 5 1 1934578X1000500 10.1177/1934578X1000500135 20184042
    [Google Scholar]
  33. Liu R. Qu Z. Lin Y. Lee C.S. Tai W.C.S. Chen S. Brevilin A induces cell cycle arrest and apoptosis in nasopharyngeal carcinoma. Front. Pharmacol. 2019 10 594 10.3389/fphar.2019.00594 31178739
    [Google Scholar]
  34. Ru J. Li P. Wang J. Zhou W. Li B. Huang C. Li P. Guo Z. Tao W. Yang Y. Xu X. Li Y. Wang Y. Yang L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform. 2014 6 1 13 10.1186/1758‑2946‑6‑13 24735618
    [Google Scholar]
  35. Wang Y. Liu M. Jafari M. Tang J. A critical assessment of traditional Chinese medicine databases as a source for drug discovery. Front. Pharmacol. 2024 15 1303693 10.3389/fphar.2024.1303693 38738181
    [Google Scholar]
  36. Li Q. Li Z. Luo T. Shi H. Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy. Mol. Biomed. 2022 3 1 47 10.1186/s43556‑022‑00110‑2 36539659
    [Google Scholar]
  37. Peng Y. Wang Y. Zhou C. Mei W. Zeng C. PI3K/Akt/mTOR pathway and its role in cancer therapeutics: Are we making headway? Front. Oncol. 2022 12 819128 10.3389/fonc.2022.819128 35402264
    [Google Scholar]
  38. Li H.L. Deng N.H. He X.S. Li Y.H. Small biomarkers with massive impacts: PI3K/AKT/mTOR signalling and microRNA crosstalk regulate nasopharyngeal carcinoma. Biomark. Res. 2022 10 1 52 10.1186/s40364‑022‑00397‑x 35883139
    [Google Scholar]
  39. Standing D. Dandawate P. Anant S. Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies. Front. Endocrinol. (Lausanne) 2023 13 1112987 10.3389/fendo.2022.1112987 36714582
    [Google Scholar]
  40. Li X. Bechara R. Zhao J. McGeachy M.J. Gaffen S.L. IL-17 receptor–based signaling and implications for disease. Nat. Immunol. 2019 20 12 1594 1602 10.1038/s41590‑019‑0514‑y 31745337
    [Google Scholar]
  41. Thanasupawat T. Glogowska A. Nivedita-Krishnan S. Wilson B. Klonisch T. Hombach-Klonisch S. Emerging roles for the relaxin/RXFP1 system in cancer therapy. Mol. Cell. Endocrinol. 2019 487 85 93 10.1016/j.mce.2019.02.001 30763603
    [Google Scholar]
  42. Manohar S.M. At the crossroads of TNF α signaling and cancer. Curr. Mol. Pharmacol. 2024 17 1 e060923220758 37691196
    [Google Scholar]
  43. Augoff K. Hryniewicz-Jankowska A. Tabola R. Stach K. MMP9: A tough target for targeted therapy for cancer. Cancers (Basel) 2022 14 7 1847 10.3390/cancers14071847 35406619
    [Google Scholar]
  44. Lin Y. Cheng A. Solanki M. Su W. Zaki M. Tirado C.A. Amplification of CCND1 in urothelial carcinoma. J. Assoc. Genet. Technol. 2022 48 1 4 9 35247258
    [Google Scholar]
  45. Zou S. Tong Q. Liu B. Huang W. Tian Y. Fu X. Targeting STAT3 in cancer immunotherapy. Mol. Cancer 2020 19 1 145 10.1186/s12943‑020‑01258‑7 32972405
    [Google Scholar]
  46. Lee H. Jeong A.J. Ye S.K. Highlighted STAT3 as a potential drug target for cancer therapy. BMB Rep. 2019 52 7 415 423 10.5483/BMBRep.2019.52.7.152 31186087
    [Google Scholar]
  47. Li L. Deng C.X. Chen Q. SRC-3, a steroid receptor coactivator: Implication in cancer. Int. J. Mol. Sci. 2021 22 9 4760 10.3390/ijms22094760 33946224
    [Google Scholar]
  48. Cai B. Qu X. Kan D. Luo Y. miR-26a-5p suppresses nasopharyngeal carcinoma progression by inhibiting PTGS2 expression. Cell Cycle 2022 21 6 618 629 10.1080/15384101.2022.2030168 35073820
    [Google Scholar]
  49. Zhou Z. Zhou Q. Wu X. Xu S. Hu X. Tao X. Li B. Peng J. Li D. Shen L. Cao Y. Yang L. VCAM-1 secreted from cancer-associated fibroblasts enhances the growth and invasion of lung cancer cells through AKT and MAPK signaling. Cancer Lett. 2020 473 62 73 10.1016/j.canlet.2019.12.039 31904479
    [Google Scholar]
  50. Hua H. Kong Q. Zhang H. Wang J. Luo T. Jiang Y. Targeting mTOR for cancer therapy. J. Hematol. Oncol. 2019 12 1 71 10.1186/s13045‑019‑0754‑1 31277692
    [Google Scholar]
  51. Eskandari E. Eaves C.J. Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. J. Cell Biol. 2022 221 6 e202201159 10.1083/jcb.202201159 35551578
    [Google Scholar]
  52. Sabbah D.A. Hajjo R. Sweidan K. Review on Epidermal Growth Factor Receptor (EGFR) structure, signaling pathways, interactions, and recent updates of EGFR inhibitors. Curr. Top. Med. Chem. 2020 20 10 815 834 10.2174/1568026620666200303123102 32124699
    [Google Scholar]
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