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2000
Volume 21, Issue 18
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Traditional Chinese medicine rarely applies the herb Safflower (Carthamus tinctorius) to the treatment of tumors and little is known about its mechanisms and the treatment of Safflower for melanoma.

Objective

This study aims to analyze the active ingredients and underlying mechanisms of Safflower in treating melanoma using network pharmacology, molecular docking, and experiments and provide a new direction for the research and development of new drugs for melanoma treatment.

Methods

We collected the active chemical ingredients from Safflower and generated a network of “Drug-Active Ingredient-Target” by Cytoscape. From the DrugBank, OMIM, and GeneCard databases, disease-related targets of melanoma were obtained. The intersection target genes between Safflower and melanoma were identified, leading to the construction of a protein-protein interaction (PPI) network Cytoscape software. Metascape database was used to enrich pathways for relative targets of Safflower. Molecular docking was demonstrated by the software AutoDockTools-1.5.6. Use an online database (https://xenabrowser.net/) and R package IOBR (version 0.99.9) to evaluate the correlation between the core target genes and prognosis or the immune score. CCK8 and PCR were used to detect the toxicity of quercetin on melanoma cells and its effects on mRNA expression of AKT1, JUN, and TP53.

Results

Our investigation identified 17 active pharmaceutical ingredients within Safflower alongside 94 potential targets related to melanoma treatment. Gene Ontology (GO) analysis is primarily concerned with extracellular exosomes, positive regulation of transcription from RNA polymerase II promoter, and protein binding. KEGG pathway enrichment analysis mainly involves Pathways in cancer, IL-17 signaling pathway, AGE-RAGE signaling pathway, and other pathways. Using molecular docking, it can be seen that the compounds Quercetin, kaempferol, luteolin, baicalein, and beta-sitosterol in Safflower have strong binding abilities with important targets. The results of survival analysis and immune score analysis suggest that Safflower may regulate the immune cell infiltration of melanoma patients by acting on core target genes and improving the prognosis of patients. analysis confirmed that Quercetin was cytotoxic toward B16-F10 cells and altered mRNA expression of AKT1, JUN, and TP53 identified through the network pharmacology approach.

Conclusion

This work offered an active pharmaceutical ingredient in Safflower and potential targets for melanoma, and the mechanism of its action on melanoma may be related to the regulation of immune-related pathways in melanoma.

© 2024 Bentham Science Publishers
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2025-09-18

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References

  1. ChapmanP.B. HauschildA. RobertC. HaanenJ.B. AsciertoP. LarkinJ. DummerR. GarbeC. TestoriA. MaioM. HoggD. LoriganP. LebbeC. JouaryT. SchadendorfD. RibasA. O’DayS.J. SosmanJ.A. KirkwoodJ.M. EggermontA.M.M. DrenoB. NolopK. LiJ. NelsonB. HouJ. LeeR.J. FlahertyK.T. McArthurG.A. Improved survival with vemurafenib in melanoma with BRAF V600E mutation.N. Engl. J. Med.2011364262507251610.1056/NEJMoa110378221639808
     [Google Scholar]
  2. RoccuzzoG. FavaP. AstruaC. BrizioM.G. CavaliereG. BongiovanniE. SantanielloU. CarpentieriG. CangiolosiL. BrondinoC. PalaV. RiberoS. QuaglinoP. Real-life outcomes of adjuvant targeted therapy and Anti-PD1 agents in stage III/IV resected melanoma.Cancers 20241617309510.3390/cancers1617309539272953
     [Google Scholar]
  3. EikenesG. LiszkayG. BalatoniT. CzirbeszK. HunyadiK. KozékiZ. KispálM.T. BaranyaiF. DanyiT. BőcsK. KenesseyI. Therapeutic and adverse effect of Anti-PD1 immunotherapy in melanoma: A retrospective, single-institute study of 222 patients.Cancers 20231515396610.3390/cancers1515396637568785
     [Google Scholar]
  4. DavisL.E. ShalinS.C. TackettA.J. Current state of melanoma diagnosis and treatment.Cancer Biol. Ther.201920111366137910.1080/15384047.2019.164003231366280
     [Google Scholar]
  5. LiM. MaH.Y. The synergistic effect of safflower injection on oxaliplatin for colon cancer liver metastasis.J. Med. Postgrad.2014271111641167
     [Google Scholar]
  6. OuyangH.P. Effects of water extracts of safflower, peach kernel and Achyranthes on inhibiting angiogenesis in transgenic zebrafish model. PhD Thesis, Chengdu University of Traditional Chinese Medicine2016
     [Google Scholar]
  7. LiuC. LeJ. BaiT.C. Effects of safflower polysaccharide on proliferation and invasion of gastric cancer MGC-803 cells.Journal of Modern Oncology20202804569573
     [Google Scholar]
  8. ZengL.J. YanngC.L. Effects and mechanism of safflower polysaccharide on proliferation and metastasis of human ovarian epithelial cancer cells.Jiangxi Medical Journal20175209901904
     [Google Scholar]
  9. ZhangJ. YaoX. LiX.M. Study on the mechanism of safflower polysaccharide on the proliferation, apoptosis and invasion of human cervical cancer Hela cells.Journal of Changzhi Medical College20173103175180
     [Google Scholar]
  10. SunW. DongS.L. ZhenY.B. Redflower polysaccharide to human colon cancer LOVO cell proliferation, apoptosis, and invasion mechanism.Anhui Yiyao2016200610451050
     [Google Scholar]
  11. ZhangY.C. GaoW.C. ChenW.J. PangD.X. MoD.Y. YangM. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Fei Jin Sheng formula in the treatment of lung cancer.Curr. Pharm. Des.202329141121113410.2174/138161282966623050316475537138492
     [Google Scholar]
  12. XuL. ZhangJ. WangY. ZhangZ. WangF. TangX. Uncovering the mechanism of Ge-Gen-Qin-Lian decoction for treating ulcerative colitis based on network pharmacology and molecular docking verification.Biosci. Rep.2021412BSR2020356510.1042/BSR2020356533409535
     [Google Scholar]
  13. ZhangR. ZhuX. BaiH. NingK. Network pharmacology databases for Traditional Chinese Medicine: Review and assessment.Front. Pharmacol.20191012310.3389/fphar.2019.0012330846939
     [Google Scholar]
  14. KitchenD.B. Computer-aided drug discovery research at a global contract research organization.J. Comput. Aided Mol. Des.201731330931810.1007/s10822‑016‑9991‑327804014
     [Google Scholar]
  15. LiangH. RuanH. OuyangQ. LaiL. Herb-target interaction network analysis helps to disclose molecular mechanism of Traditional Chinese Medicine.Sci. Rep.2016613676710.1038/srep3676727833111
     [Google Scholar]
  16. MorrisG.M. Lim-WilbyM. Molecular docking.Methods Mol. Biol.200844336538210.1007/978‑1‑59745‑177‑2_1918446297
     [Google Scholar]
  17. RuJ. LiP. WangJ. ZhouW. LiB. HuangC. LiP. GuoZ. TaoW. YangY. XuX. LiY. WangY. YangL. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑1324735618
     [Google Scholar]
  18. WishartD.S. FeunangY.D. GuoA.C. LoE.J. MarcuA. GrantJ.R. SajedT. JohnsonD. LiC. SayeedaZ. AssempourN. IynkkaranI. LiuY. MaciejewskiA. GaleN. WilsonA. ChinL. CummingsR. LeD. PonA. KnoxC. WilsonM. DrugBank 5.0: a major update to the DrugBank database for 2018.Nucleic Acids Res.201846D1D1074D108210.1093/nar/gkx103729126136
     [Google Scholar]
  19. AmbergerJ.S. BocchiniC.A. SchiettecatteF. ScottA.F. HamoshA. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders.Nucleic Acids Res.201543D1D789D79810.1093/nar/gku120525428349
     [Google Scholar]
  20. StelzerG RosenN PlaschkesI The genecards suite: From gene data mining to disease genome sequence analyses. Current Protocols in Bioinformatics2016541.30.1
  21. OliverosJ.C. Venny. An Interactive Tool for Comparing Lists with Venn’s Diagrams. 2007-2015 Available from: https://bioinfogp.cnb.csic.es/tools/venny/index.html
  22. LongHua Hospital Shanghai University of Traditional Chinese Medicine,YangMing. TCM Network Pharmacology Analysis System v1.0[CP/CD],Copyright Registration No.,2019SR1127090.
  23. Fernández-CortésM. Delgado-BellidoD. Bermúdez-JiménezE. ParamioJ.M. O’ValleF. VinckierS. CarmelietP. Garcia-DiazA. OliverF.J. PARP inhibition promotes endothelial‐like traits in melanoma cells and modulates pericyte coverage dynamics during vasculogenic mimicry.J. Pathol.2023259331833010.1002/path.604336484652
     [Google Scholar]
  24. NguyenN.T. NguyenT.H. PhamT.N.H. HuyN.T. BayM.V. PhamM.Q. NamP.C. VuV.V. NgoS.T. Autodock vina adopts more accurate binding poses but autodock4 forms better binding affinity.J. Chem. Inf. Model.202060120421110.1021/acs.jcim.9b0077831887035
     [Google Scholar]
  25. McMillanD. Martinez-FleitesC. PorterJ. FoxD.III DavisR. MoriP. CeskaT. CarringtonB. LawsonA. BourneT. O’ConnellJ. Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF.Nat. Commun.202112158210.1038/s41467‑020‑20828‑333495441
     [Google Scholar]
  26. ShawS. BourneT. MeierC. CarringtonB. GelinasR. HenryA. PopplewellA. AdamsR. BakerT. RapeckiS. MarshallD. MooreA. NealeH. LawsonA. Discovery and characterization of olokizumab.MAbs20146377378110.4161/mabs.2861224670876
     [Google Scholar]
  27. RichardsM.W. BurgessS.G. Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors.Proceedings of the National Academy of Sciences of the United States of America20161372631
     [Google Scholar]
  28. DayP.J. Crystal structure of human CDK4 in complex with a D-type cyclin.Proceedings of the National Academy of Sciences of the United States of America2009416670
     [Google Scholar]
  29. MandalK. UppalapatiM. Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.Proceedings of the National Academy of Sciences of the United States of America20121477984
     [Google Scholar]
  30. AddieM. BallardP. ButtarD. CrafterC. CurrieG. DaviesB.R. DebreczeniJ. DryH. DudleyP. GreenwoodR. JohnsonP.D. KettleJ.G. LaneC. LamontG. LeachA. LukeR.W.A. MorrisJ. OgilvieD. PageK. PassM. PearsonS. RustonL. Discovery of 4-Amino-N-[(1 S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7 H -pyrrolo[2,3- d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases.J. Med. Chem.20135652059207310.1021/jm301762v23394218
     [Google Scholar]
  31. WangD. StroudJ.C. ChenL. Crystal Structure of Human NFAT1 and Fos-Jun on the IL-2 ARRE1 Site.2005Available from https://pdbj.org/search/pdb-author?query=%22Wang%2C+D.%22
    [Google Scholar]
  32. PettyT.J. EmamzadahS. CostantinoL. PetkovaI. StavridiE.S. SavenJ.G. VautheyE. HalazonetisT.D. An induced fit mechanism regulates p53 DNA binding kinetics to confer sequence specificity.EMBO J.201130112167217610.1038/emboj.2011.12721522129
     [Google Scholar]
  33. MaciagJ.J. MackenzieS.H. TuckerM.B. SchipperJ.L. SwartzP. ClarkA.C. Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.Proc. Natl. Acad. Sci. USA201611341E6080E608810.1073/pnas.160354911327681633
     [Google Scholar]
  34. FreedD.M. BessmanN.J. KiyatkinA. Salazar-CavazosE. ByrneP.O. MooreJ.O. ValleyC.C. FergusonK.M. LeahyD.J. LidkeD.S. LemmonM.A. EGFR Ligands differentially stabilize receptor dimers to specify signaling kinetics.Cell20171713683695.e1810.1016/j.cell.2017.09.01728988771
     [Google Scholar]
  35. SharmaP. Hu-LieskovanS. WargoJ.A. RibasA. Primary, adaptive, and acquired resistance to cancer immunotherapy.Cell2017168470772310.1016/j.cell.2017.01.01728187290
     [Google Scholar]
  36. ZhaoP. HeX.B. ChenX.Y. LiZ.L. XingW.J. LiuW. RenC. HanX.D. GuoB. Celastrol inhibits mouse B16-F10 melanoma cell survival by regulating the PI3K/AKT/mTOR signaling pathway and repressing HIF-1α expression.Discov. Oncol.202415117810.1007/s12672‑024‑01045‑638771435
     [Google Scholar]
  37. DouM. ZhuD. CuiG. LiH. DiL. WangL. Euphorbia helioscopia L. exhibits promising therapeutic effects on hemangioendothelioma and melanoma through angiogenesis inhibition.Phytomedicine202412915566610.1016/j.phymed.2024.15566638678953
     [Google Scholar]
  38. YangX. WuM. YanX. ZhangC. LuoY. YuJ. Pulsatilla saponins inhibit experimental lung metastasis of melanoma via targeting STAT6-Mediated M2 macrophages polarization.Molecules2023289368210.3390/molecules2809368237175092
     [Google Scholar]
  39. QiangD. CiC. LiuW. WangJ. HeC. JiB. ShaoX. Inhibitory effect of kaempferol on mouse melanoma cell line B16 in vivo and in vitro.Postepy Dermatol. Alergol.202138349850410.5114/ada.2020.9425734377134
     [Google Scholar]
  40. YaoX. JiangW. YuD. YanZ. Luteolin inhibits proliferation and induces apoptosis of human melanoma cells in vivo and in vitro by suppressing MMP-2 and MMP-9 through the PI3K/AKT pathway.Food Funct.201910270371210.1039/C8FO02013B30663726
     [Google Scholar]
  41. ShafabakhshR. AsemiZ. Quercetin: a natural compound for ovarian cancer treatment.J. Ovarian Res.20191215510.1186/s13048‑019‑0530‑431202269
     [Google Scholar]
  42. HussainY. MirzaeiS. AshrafizadehM. ZarrabiA. HushmandiK. KhanH. DagliaM. Quercetin and its nano-scale delivery systems in prostate cancer therapy: Paving the way for cancer elimination and reversing chemoresistance.Cancers 2021137160210.3390/cancers1307160233807174
     [Google Scholar]
  43. LeiC.S. HouY.C. PaiM.H. LinM.T. YehS.L. Effects of quercetin combined with anticancer drugs on metastasis-associated factors of gastric cancer cells: in vitro and in vivo studies.J. Nutr. Biochem.20185110511310.1016/j.jnutbio.2017.09.01129125991
     [Google Scholar]
  44. SollF. TernentC. BerryI.M. KumariD. MooreT.C. Quercetin inhibits proliferation and induces apoptosis of B16 melanoma cells in vitro.Assay Drug Dev. Technol.202018626126810.1089/adt.2020.99332799543
     [Google Scholar]
  45. PiipponenM. RiihiläP. NissinenL. KähäriV.M. The role of p53 in progression of cutaneous squamous cell carcinoma.Cancers (Basel)20211318450710.3390/cancers1318450734572732
     [Google Scholar]
  46. WeissJ. HeineM. ArdenK.C. KörnerB. PilchH. HerbstR.A. JungE.G. Mutation and expression of TP53 in malignant melanomas.Recent Results Cancer Res.199513913715410.1007/978‑3‑642‑78771‑3_107597286
     [Google Scholar]
  47. ParikhR. ParikhS. BerzinD. VaknineH. OvadiaS. LikonenD. GreenbergerS. ScopeA. ElgavishS. NevoY. PlaschkesI. NizriE. KobilerO. MaliahA. ZarembaL. MohanV. SagiI. Ashery-PadanR. CarmiY. LuxenburgC. HoheiselJ.D. KhaledM. LevesqueM.P. LevyC. Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.EMBO J.202443173553358610.1038/s44318‑024‑00103‑738719996
     [Google Scholar]
  48. HammoudaM. FordA. LiuY. ZhangJ. The JNK signaling pathway in inflammatory skin disorders and cancer.Cells20209485710.3390/cells904085732252279
     [Google Scholar]
  49. HuH. ZhangY. ZhaoL. ZhaoW. WangX. YeE. DongY. ZhangL. RanF. ZhouY. HuangY. AFF4 facilitates melanoma cell progression by regulating c-Jun activity.Exp. Cell Res.2021399211244510.1016/j.yexcr.2020.11244533417923
     [Google Scholar]
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Exploring the Mechanism of the Safflower against Melanoma using Network Pharmacology and Molecular Docking
Letters in Drug Design & Discovery 21, 4508 (2024); https://doi.org/10.2174/0115701808320244241216044645
/content/journals/lddd/10.2174/0115701808320244241216044645
/content/journals/lddd/10.2174/0115701808320244241216044645
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  • Article Type:     Research Article
Keyword(s): bioinformatics; melanoma; molecular docking; network pharmacology; quercetin; Safflower

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