Skip to content
2000
Volume 31, Issue 5
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Background

(PS), the spike from L., is a traditional Chinese medicine that can treat Oral Squamous Cell Carcinoma (OSCC), whereas its molecular mechanisms and effects on the prognosis of patients remain unclear.

Methods

Our study aimed to identify the potential anti-OSCC targets of PS and explore its mechanisms and effects on prognosis through network pharmacology, bioinformatics analysis, molecular docking, and cell assays.

Results

Sixty-two potential targets of 11 active anti-OSCC ingredients of PS were identified, with Quercetin, the core ingredient of PS, exhibiting the most significant number of OSCC-related targets. GO analysis indicated that the primary biological processes involved in OSCC treatment by PS were the cellular response to nitrogen compound, response to xenobiotic stimulus, and cellular response to organonitrogen compound. KEGG analysis revealed that pathways in cancer were the top highly enriched signaling pathway in the treatment of OSCC by PS. DisGeNET analysis is mainly about Lip and Oral Cavity Carcinoma. More importantly, 6 of the 62 targets were markedly related to prognosis. Molecular docking revealed high affinities between the key component and the prognosis-related target proteins. Treatment of OSCC cell line SCC-25 with Quercetin could inhibit malignant biological behaviors, such as cell proliferation, colony formation, invasion, and migration, as well as affect the targets related to prognosis and promote autophagy.

Conclusion

Overall, these results suggest that PS plays a significant role in treating and improving the prognosis of OSCC by directly influencing various processes in OSCC.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128328547240827045955
2023-09-16
2025-04-06
Loading full text...

Full text loading...

References

  1. SungH. FerlayJ. SiegelR.L. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
    [Google Scholar]
  2. BaganJ. SarrionG. JimenezY. Oral cancer: Clinical features.Oral Oncol.201046641441710.1016/j.oraloncology.2010.03.009 20400366
    [Google Scholar]
  3. CaoM. ShiE. WangH. Personalized targeted therapeutic strategies against oral squamous cell carcinoma. An evidence-based review of literature.Int. J. Nanomedicine2022174293430610.2147/IJN.S377816 36134201
    [Google Scholar]
  4. KågedalÅ. MargolinG. HeldC. A novel sentinel lymph node approach in oral squamous cell carcinoma.Curr. Pharm. Des.202026313834383910.2174/1381612826666200213100750 32053068
    [Google Scholar]
  5. ZanoniD.K. MonteroP.H. MigliacciJ.C. Survival outcomes after treatment of cancer of the oral cavity (1985-2015).Oral Oncol.20199011512110.1016/j.oraloncology.2019.02.001 30846169
    [Google Scholar]
  6. VaidyaM. DmelloC. MogreS. Utility of keratins as biomarkers for human oral precancer and cancer.Life202212334310.3390/life12030343 35330094
    [Google Scholar]
  7. WangD. DuanX. ZhangY. MengZ. WangJ. Traditional Chinese medicine for oral squamous cell carcinoma.Medicine 20209943e2295510.1097/MD.0000000000022955 33120858
    [Google Scholar]
  8. WangS.J. WangX.H. DaiY.Y. Prunella vulgaris: A comprehensive review of chemical constituents, pharmacological effects and clinical applications.Curr. Pharm. Des.201925335936910.2174/1381612825666190313121608 30864498
    [Google Scholar]
  9. RaoP.L. ShenY.H. SongY.J. XuY. XuH.X. Prunella vulgaris L. attenuates gut dysbiosis and endotoxin leakage against alcoholic liver disease.J. Ethnopharmacol.2024319Pt 211723710.1016/j.jep.2023.117237 37769885
    [Google Scholar]
  10. MirR.H. BhatM.F. SawhneyG. Prunella vulgaris L: Critical pharmacological, expository traditional uses and extensive phytochemistry: A review.Curr. Drug Discov. Technol.2022191e14012219110210.2174/1570163818666210203181542 33538676
    [Google Scholar]
  11. PanJ. WangH. ChenY. Prunella vulgaris L. – A review of its ethnopharmacology, phytochemistry, quality control and pharmacological effects.Front. Pharmacol.20221390317110.3389/fphar.2022.903171 35814234
    [Google Scholar]
  12. LuoH. ZhaoL. LiY. An in vivo and in vitro assessment of the anti-breast cancer activity of crude extract and fractions from Prunella vulgaris L.Heliyon2022811e1118310.1016/j.heliyon.2022.e11183 36345524
    [Google Scholar]
  13. ChoiJ.H. HanE.H. HwangY.P. ChoiJ.M. ChoiC.Y. ChungY.C. Suppression of PMA-induced tumor cell invasion and metastasis by aqueous extract isolated from Prunella vulgaris via the inhibition of NF-kappaB-dependent MMP-9 expression.Food Chem. Toxicol.2010482564571
    [Google Scholar]
  14. ZhaoJ. JiD. ZhaiX. ZhangL. LuoX. FuX. Oral administration of Prunella vulgaris L improves the effect of taxane on preventing the progression of breast cancer and reduces its side effects.Front. Pharmacol.2018980610.3389/fphar.2018.00806 30123125
    [Google Scholar]
  15. ZhuK.K. LiY.C. TanJ. Professor Li Yuancong’s clinical experience in treating oral carcinoma.J Hunan Univ Chinese Med2021410914221426
    [Google Scholar]
  16. LiF. SunZ. Chemopreventive effect of Prunella vulgaris L. on DMBA-induced oral precancerous lesions.Chin J Pract Stomatol2009206342344
    [Google Scholar]
  17. WangY. YaoR. GaoS. Chemopreventive effect of a mixture of Chinese herbs (antitumor B) on chemically induced oral carcinogenesis.Mol. Carcinog.2013521495610.1002/mc.20877 22086836
    [Google Scholar]
  18. SunZ. GuanX. LiN. LiuX. ChenX. Chemoprevention of oral cancer in animal models, and effect on leukoplakias in human patients with ZengShengPing, a mixture of medicinal herbs.Oral Oncol.201046210511010.1016/j.oraloncology.2009.06.004 20022553
    [Google Scholar]
  19. GuanX.B. SunZ. ChenX.X. WuH.R. ZhangX.Y. Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters.Chin. Med. J. 20121252332337 22340569
    [Google Scholar]
  20. WangJ. WangS. WangY. Chemopreventive effect of modified Zengshengping on oral cancer in a hamster model and assessment of its effect on liver.J. Ethnopharmacol.202025511277410.1016/j.jep.2020.112774 32198081
    [Google Scholar]
  21. ZhangR. ZhuX. BaiH. NingK. Network pharmacology databases for traditional Chinese medicine: Review and assessment.Front. Pharmacol.20191012310.3389/fphar.2019.00123 30846939
    [Google Scholar]
  22. ZengP. FangM. ZhaoH. GuoJ. A network pharmacology approach to uncover the key ingredients in Ginkgo folium and their anti-Alzheimer’s disease mechanisms.Aging 20211314189931901210.18632/aging.203348 34315132
    [Google Scholar]
  23. HouF. LiuY. ChengY. ZhangN. YanW. ZhangF. Exploring the mechanism of Scutellaria baicalensis Georgi efficacy against oral squamous cell carcinoma based on network pharmacology and molecular docking analysis.Evidence-Based Complement. Altern. Med.202120215597586
    [Google Scholar]
  24. ZhangL. LingZ. HuZ. MengG. ZhuX. TangH. Huanglianjiedu decoction as an effective treatment for oral squamous cell carcinoma based on network pharmacology and experimental validation.Cancer Cell Int.202121155310.1186/s12935‑021‑02201‑6 34674717
    [Google Scholar]
  25. LiL. LiJ. ChenH. Azoxystrobin induces apoptosis via PI3K/AKT and MAPK signal pathways in oral leukoplakia progression.Front. Pharmacol.20221391208410.3389/fphar.2022.912084 35991869
    [Google Scholar]
  26. RuJ. LiP. WangJ. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑13 24735618
    [Google Scholar]
  27. DainaA. MichielinO. ZoeteV. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.Sci. Rep.2017714271710.1038/srep42717 28256516
    [Google Scholar]
  28. StelzerG RosenN PlaschkesI ZimmermanS TwikM FishilevichS. The genecards suite: From gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics201654 303133
  29. AmbergerJ.S. HamoshA. Searching online mendelian inheritance in man (OMIM): A knowledgebase of human genes and genetic phenotypes.Curr. Protoc. Bioinformatics201758112
    [Google Scholar]
  30. ShannonP. MarkielA. OzierO. Cytoscape: A software environment for integrated models of biomolecular interaction networks.Genome Res.200313112498250410.1101/gr.1239303 14597658
    [Google Scholar]
  31. SzklarczykD. GableA.L. NastouK.C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets.Nucleic Acids Res.202149D1D605D61210.1093/nar/gkaa1074 33237311
    [Google Scholar]
  32. ZhouY. ZhouB. PacheL. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.Nat. Commun.2019101152310.1038/s41467‑019‑09234‑6 30944313
    [Google Scholar]
  33. TomczakK. CzerwińskaP. WiznerowiczM. Review the cancer genome atlas (TCGA): An immeasurable source of knowledge.Contemp. Oncol.20151A1A687710.5114/wo.2014.47136 25691825
    [Google Scholar]
  34. GoldmanM.J. CraftB. HastieM. Visualizing and interpreting cancer genomics data via the Xena platform.Nat. Biotechnol.202038667567810.1038/s41587‑020‑0546‑8 32444850
    [Google Scholar]
  35. KimS. ChenJ. ChengT. PubChem in 2021: New data content and improved web interfaces.Nucleic Acids Res.202149D1D1388D139510.1093/nar/gkaa971 33151290
    [Google Scholar]
  36. UniProt A worldwide hub of protein knowledge.Nucleic Acids Res.201947D1D506D51510.1093/nar/gky1049 30395287
    [Google Scholar]
  37. BurleyS.K. BhikadiyaC. BiC. RCSB Protein Data Bank: Powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences.Nucleic Acids Res.202149D1D437D45110.1093/nar/gkaa1038 33211854
    [Google Scholar]
  38. TrottO. OlsonA.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem.201031245546110.1002/jcc.21334 19499576
    [Google Scholar]
  39. LipinskiC.A. LombardoF. DominyB.W. FeeneyP.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.Adv. Drug Deliv. Rev.2001461-332610.1016/S0169‑409X(00)00129‑0 11259830
    [Google Scholar]
  40. VeberD.F. JohnsonS.R. ChengH.Y. SmithB.R. WardK.W. KoppleK.D. Molecular properties that influence the oral bioavailability of drug candidates.J. Med. Chem.200245122615262310.1021/jm020017n 12036371
    [Google Scholar]
  41. KawabataK. MukaiR. IshisakaA. Quercetin and related polyphenols: New insights and implications for their bioactivity and bioavailability.Food Funct.2015651399141710.1039/C4FO01178C 25761771
    [Google Scholar]
  42. HuangC.Y. ChanC.Y. ChouI.T. LienC.H. HungH.C. LeeM.F. Quercetin induces growth arrest through activation of FOXO1 transcription factor in EGFR-overexpressing oral cancer cells.J. Nutr. Biochem.20132491596160310.1016/j.jnutbio.2013.01.010 23618529
    [Google Scholar]
  43. ChanC.Y. HongS.C. ChangC.M. ChenY.H. LiaoP.C. HuangC.Y. Oral squamous cell carcinoma cells with acquired resistance to erlotinib are sensitive to anti-cancer effect of quercetin via pyruvate kinase M2 (PKM2).Cells202312117910.3390/cells12010179 36611972
    [Google Scholar]
  44. DikovaV. Jantus-LewintreE. BaganJ. Potential non-invasive biomarkers for early diagnosis of oral squamous cell carcinoma.J. Clin. Med.2021108165810.3390/jcm10081658 33924500
    [Google Scholar]
  45. LaiK.C. LiuC.J. LinT.J. Blocking TNF-α inhibits angiogenesis and growth of IFIT2-depleted metastatic oral squamous cell carcinoma cells.Cancer Lett.2016370220721510.1016/j.canlet.2015.10.016 26515391
    [Google Scholar]
  46. AubreyB.J. StrasserA. KellyG.L. Tumor-suppressor functions of the TP53 pathway.Cold Spring Harb. Perspect. Med.201665a02606210.1101/cshperspect.a026062 27141080
    [Google Scholar]
  47. Gleber-NettoF.O. NeskeyD. CostaA.F.M. Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma.Cancer2020126204498451010.1002/cncr.33101 32797678
    [Google Scholar]
  48. Claesson-WelshL. WelshM. VEGFA and tumour angiogenesis.J. Intern. Med.2013273211412710.1111/joim.12019 23216836
    [Google Scholar]
  49. ZhaoC. ZhouY. MaH. WangJ. GuoH. LiuH. A four-hypoxia-genes-based prognostic signature for oral squamous cell carcinoma.BMC Oral Health202121123210.1186/s12903‑021‑01587‑z 33941139
    [Google Scholar]
  50. PeterleG.T. MaiaL.L. TrivilinL.O. de OliveiraM.M. Dos SantosJ.G. MendesS.O. PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.J. Oral Pathol. Med.2018476566574
    [Google Scholar]
  51. MengQ. XiaY. c-Jun, at the crossroad of the signaling network.Protein Cell201121188989810.1007/s13238‑011‑1113‑3 22180088
    [Google Scholar]
  52. AlamM. KashyapT. PramanikK.K. SinghA.K. NaginiS. MishraR. The elevated activation of NFκB and AP-1 is correlated with differential regulation of Bcl-2 and associated with oral squamous cell carcinoma progression and resistance.Clin. Oral Investig.20172192721273110.1007/s00784‑017‑2074‑6 28233171
    [Google Scholar]
  53. SigismundS. AvanzatoD. LanzettiL. Emerging functions of the EGFR in cancer.Mol. Oncol.201812132010.1002/1878‑0261.12155 29124875
    [Google Scholar]
  54. WongpattaraworakulW. Gibson-CorleyK.N. ChoiA. Prognostic role of combined EGFr and tumor-infiltrating lymphocytes in oral squamous cell carcinoma.Front. Oncol.20221288523610.3389/fonc.2022.885236 35957892
    [Google Scholar]
  55. JingZ. JingH. JingZ. FangC. ShiH. RongZ. Influence of traditional Chinese medicine Prunella vulgaris on fas ligand gene expression and invasive ability of human bladder cancer cell.Xiandai Shengwu Yixue Jinzhan2010101426282631
    [Google Scholar]
  56. GaoW. XuH. Root extract of Prunella vulgaris inhibits in vitro and in vivo carcinogenesis in MCF-5 human breast carcinoma via suppression of angiogenesis, induction of apoptosis, cell cycle arrest and modulation of PI3K/AKT signalling pathway.JBUON2019242549554
    [Google Scholar]
  57. ZhuJ. ZhangW. ZhangY. WangY. LiuM. LiuY. Effects of Spica prunellae on caspase-3-associated proliferation and apoptosis in human lung cancer cells in vitro.J. Cancer Res. Ther.201814476076310.4103/jcrt.JCRT_1289_16 29970649
    [Google Scholar]
  58. LiuW. JinW. ZhuS. ChenY. LiuB. Targeting regulated cell death (RCD) with small-molecule compounds in cancer therapy: A revisited review of apoptosis, autophagy-dependent cell death and necroptosis.Drug Discov. Today202227261262510.1016/j.drudis.2021.10.011 34718209
    [Google Scholar]
  59. GouQ. ZhengL.L. HuangH. Unravelling the roles of autophagy in OSCC: A renewed perspective from mechanisms to potential applications.Front. Pharmacol.20221399464310.3389/fphar.2022.994643 36263139
    [Google Scholar]
  60. SongJ. ZhangZ. HuY. LiZ. WanY. LiuJ. An aqueous extract of Prunella vulgaris L. inhibits the growth of papillary thyroid carcinoma by inducing autophagy in vivo and in vitro.Phytother. Res.202135526912702
    [Google Scholar]
  61. SongY. KangL. TianS. Study on the anti-hepatocarcinoma effect and molecular mechanism of Prunella vulgaris total flavonoids.J. Ethnopharmacol.202127311389110.1016/j.jep.2021.113891 33675913
    [Google Scholar]
  62. AminMB. GreeneFL. EdgeSB. ComptonCC. GershenwaldJE. BrooklandRK. The eighth edition AJCC cancer staging manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA: A Cancer J Clin2017672939
    [Google Scholar]
  63. HuangS.H. O’SullivanB. Overview of the 8th edition TNM classification for head and neck cancer. Curr Treat Options Oncol 201718740
    [Google Scholar]
  64. WuC.S. ChangI.Y.F. HungJ. ASC modulates HIF-1α stability and induces cell mobility in OSCC.Cell Death Dis.202011972110.1038/s41419‑020‑02927‑7 32883954
    [Google Scholar]
  65. KumariP. KumarS. SethyM. BhueS. MohantaB.K. DixitA. Identification of therapeutically potential targets and their ligands for the treatment of OSCC.Front. Oncol.20221291049410.3389/fonc.2022.910494 36203433
    [Google Scholar]
  66. YokokawaM. MoritaK.I. OikawaY. KayamoriK. SakamotoK. IkedaT. Co-expression of EGFR and MET has a synergistic effect on the prognosis of patients with oral squamous cell carcinoma.J. Oral Pathol. Med.2020493235242
    [Google Scholar]
  67. WuY.H. Yu-Fong ChangJ. ChiangC.P. WangY.P. Combined evaluation of both WEE1 and phosphorylated cyclin dependent kinase 1 expressions in oral squamous cell carcinomas predicts cancer recurrence and progression.J. Dent. Sci.20221741780178710.1016/j.jds.2022.08.009 36299328
    [Google Scholar]
  68. KujanO. HuangG. RavindranA. VijayanM. FarahC.S. CDK4, CDK6, cyclin D1 and Notch1 immunocytochemical expression of oral brush liquid-based cytology for the diagnosis of oral leukoplakia and oral cancer.J. Oral Pathol. Med.2019487566573
    [Google Scholar]
  69. CheJ. ZhaoT. LiuW. Neochlorogenic acid enhances the antitumor effects of pingyangmycin via regulating TOP2A.Mol. Med. Rep.202023215810.3892/mmr.2020.11797 33355372
    [Google Scholar]
  70. SuY.C. LinI.H. SiaoY.M. LiuC.J. YehC.C. Modulation of the tumor metastatic microenvironment and multiple signal pathways by Prunella vulgaris in human hepatocellular carcinoma.Am. J. Chin. Med.201644483584910.1142/S0192415X16500464 27222069
    [Google Scholar]
  71. TanJ. QiH. NiJ. Extracts of endophytic fungus xkc-s03 from Prunella vulgaris L. spica inhibit gastric cancer in vitro and in vivo.Oncol. Lett.20159294594910.3892/ol.2014.2722 25624914
    [Google Scholar]
  72. LinW. ZhengL. ZhuangQ. Spica prunellae promotes cancer cell apoptosis, inhibits cell proliferation and tumor angiogenesis in a mouse model of colorectal cancer via suppression of STAT3 pathway.BMC Complement. Altern. Med.201313114410.1186/1472‑6882‑13‑144 23800091
    [Google Scholar]
  73. HuangS. CuiM. WangR. Combined treatment with Prunella vulgaris and Radix bupleuri activated the Bax/Bcl-2 and Caspase-3 signal pathways in papillary thyroid carcinoma cells.Nucleosides Nucleotides Nucleic Acids202342973174210.1080/15257770.2023.2189464 36924446
    [Google Scholar]
  74. FangY. YangC. ZhangL. Spica prunellae extract enhances fluorouracil sensitivity of 5-fluorouracil-resistant human colon carcinoma HCT-8/5-FU cells via TOP2 α and miR-494.BioMed Res. Int.2019201911210.1155/2019/5953619 31662984
    [Google Scholar]
  75. HuipingW. TuanzhuH. MingG. Prunella vulgaris L. extract decreasing mRNA expressions of α-glucosidase SGLT-1, GLUT-2 and Na~+-K~+-ATPase in Caco-2 cells.Chin J Biochem Pharm20103106373376
    [Google Scholar]
  76. AndresS. PevnyS. ZiegenhagenR. Safety aspects of the use of quercetin as a dietary supplement.Mol. Nutr. Food Res.2018621170044710.1002/mnfr.201700447 29127724
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128328547240827045955
Loading
/content/journals/cpd/10.2174/0113816128328547240827045955
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