Network pharmacology-integrated molecular docking analysis of phytocompounds of Caesalpinia pulcherrima (peacock flower) as potential anti-metastatic agents

References

• Aalinkeel, R., Nair, B. B., Reynolds, J. L., Sykes, D. E., Mahajan, S. D., Chadha, K. C., & Schwartz, S. A. (2011). Overexpression of MMP-9 contributes to invasiveness of prostate cancer cell line LNCaP. Immunological Investigations, 40(5), 447–464. https://doi.org/10.3109/08820139.2011.557795
   PubMed Web of Science ®Google Scholar
• Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., & Lindahl, E. (2015). GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 1-2, 19–25. https://doi.org/10.1016/j.softx.2015.06.001
   Google Scholar
• Alsayari, A., Muhsinah, A. B., Hassan, M. Z., Ahsan, M. J., Alshehri, J. A., & Begum, N. (2019). Aurone: A biologically attractive scaffold as anticancer agent. European Journal of Medicinal Chemistry, 166, 417–431. https://doi.org/10.1016/j.ejmech.2019.01.078
   PubMed Web of Science ®Google Scholar
• Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., & Sherlock, G. (2000). Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nature Genetics, 25(1), 25–29. https://doi.org/10.1038/75556
   PubMed Web of Science ®Google Scholar
• Azmi, A. S., Wang, Z., Philip, P. A., Mohammad, R. M., & Sarkar, F. H. P. (2010). Proof of concept: Network and systems biology approaches aid in the discovery of potent anticancer drug combinations. Molecular Cancer Therapeutics, 9(12), 3137–3144. https://doi.org/10.1158/1535-7163.MCT-10-0642
   PubMed Web of Science ®Google Scholar
• Belotti, D., Paganoni, P., Manenti, L., Garofalo, A., Marchini, S., Taraboletti, G., & Giavazzi, R. (2003). Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: Implications for ascites formation. Cancer Res, 63(17), 5224–5229.
   PubMed Web of Science ®Google Scholar
• Bhattacharyya, N., Gupta, S., Sharma, S., Soni, A., Bagabir, S. A., Bhattacharyya, M., Mukherjee, A., Almalki, A. H., Alkhanani, M. F., Haque, S., Ray, A. K., & Malik, M. Z. (2022). CDK1 and HSP90AA1 Appear as the Novel Regulatory Genes in Non-Small Cell [67] Lung Cancer: A Bioinformatics Approach. Journal of Personalized Medicine, 12(3), 393–393. https://doi.org/10.3390/jpm12030393
   PubMed Web of Science ®Google Scholar
• Chakravarty, D., Nair, S. S., Santhamma, B., Nair, B. C., Wang, L., Bandyopadhyay, A., Agyin, J. K., Brann, D., Sun, L. Z., Yeh, I. T., Lee, F. Y., Tekmal, R. R., Kumar, R., & Vadlamudi, R. K. (2010). Extranuclear functions of ER impact invasive migration and metastasis by breast cancer cells. Cancer Research, 70(10), 4092–4101. https://doi.org/10.1158/0008-5472.CAN-09-3834
   PubMed Web of Science ®Google Scholar
• Chan, G. C. K., Rave, T., Yan, S. W., Chia, A. Y. Y., Yap, W. H., & Tang, Y. Q. (2021). Biological Properties of Stigmasterol and other Phytosterols. Malaysian Journal of Biochemistry & Molecular Biology, 1, 52–64.
   Google Scholar
• Chen, X., Gu, J., Neuwald, A. F., Hilakivi-Clarke, L., Clarke, R., & Xuan, J. (2021). Identifying intracellular signaling modules and exploring pathways associated with breast cancer recurrence. Scientific Reports, 11(1), 385. https://doi.org/10.1038/s41598-020-79603-5
   PubMed Web of Science ®Google Scholar
• Chen, X. L., Liu, L. C., Xu, Z. G., Li, Z., Li, R. W., Gao, R. J., Wang, S., Zhang, M., & Guo, H. (2008). [Inhibition of bladder cancer cell growth and angiogenesis by co-blockage of vascular endothelial growth factor and its receptor KDR]. Zhonghua Zhong Liu Za Zhi, 30(8), 578–582.
   PubMedGoogle Scholar
• Cho, J. H., Robinson, J. P., Arave, R. A., Burnett, W. J., Kircher, D. A., Chen, G., Davies, M. A., Grossmann, A. H., VanBrocklin, M. W., McMahon, M., & Holmen, S. L. (2015). AKT1 Activation Promotes Development of Melanoma Metastases. Cell Reports, 13(5), 898–905. https://doi.org/10.1016/j.celrep.2015.09.057
   PubMed Web of Science ®Google Scholar
• Chu, C., Liu, X., Bai, X., Zhao, T., Wang, M., Xu, R., Li, M., Hu, Y., Li, W., Yang, L., Qin, Y., Yang, M., Yan, C., & Zhang, Y. (2018). MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3. International Journal of Biological Sciences, 14(2), 228–236. https://doi.org/10.7150/ijbs.22849
   PubMed Web of Science ®Google Scholar
• Cipolletti, M., Bartoloni, S., Busonero, C., Parente, M., Leone, S., & Acconcia, F. (2021). A New Anti-Estrogen Discovery Platform Identifies FDA-Approved Imidazole Anti-Fungal Drugs as Bioactive Compounds against ERα Expressing Breast Cancer Cells. International Journal of Molecular Sciences, 22(6), 2915. https://doi.org/10.3390/ijms22062915
   PubMed Web of Science ®Google Scholar
• Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with PyRx. In Chemical biology. (pp. 243–250): Humana Press.
   Google Scholar
• Das, S. K., Deka, S. J., Paul, D., Gupta, D. D., Das, T. J., Maravi, D. K., Tag, H., & Hui, P. K. (2022). In-silico based identification of phytochemicals from Houttuynia cordata Thunb. as potential inhibitors for overexpressed HER2 and VEGFR2 cancer genes. Journal of Biomolecular Structure & Dynamics, 40(15), 6857–6867. https://doi.org/10.1080/07391102.2021.1891136
   PubMed Web of Science ®Google Scholar
• Davies, B., Waxman, J., Wasan, H., Abel, P., Williams, G., Krausz, T., Neal, D., Thomas, D., Hanby, A., & Balkwill, F. (1993). Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion. Cancer Res, 53(22), 5365–5369.
   PubMed Web of Science ®Google Scholar
• Dolgalev, I. (2022). msigdbr: MSigDB Gene Sets for Multiple Organisms in a Tidy Data Format. R Package Version, 7(5), 1–1.
   Google Scholar
• Dueñas, M., Martínez-Fernández, M., García-Escudero, R., Villacampa, F., Marqués, M., Saiz-Ladera, C., Duarte, J., Martínez, V., Gómez, M. J., Martín, M. L., Fernández, M., Castellano, D., Real, F. X., Rodriguez-Peralto, J. L., De La Rosa, F., & Paramio, J. M. (2015). PIK3CA gene alterations in bladder cancer are frequent and associate with reduced recurrence in non-muscle invasive tumors. Molecular Carcinogenesis, 54(7), 566–576. https://doi.org/10.1002/mc.22125
   PubMed Web of Science ®Google Scholar
• Elgoyhen, A. B., Langguth, B., Vanneste, S., & De Ridder, D. (2012). Tinnitus: Network pathophysiology-network pharmacology. Frontiers in Systems Neuroscience, 6(1), 1. https://doi.org/10.3389/fnsys.2012.00001
   PubMedGoogle Scholar
• Elkaeed, E. B., Khalifa, M., M., Alsfouk, B. A., Alsfouk, A. A., El-Attar, A. M. M., Eissa, I. H., Metwaly,., & A., M. (2022). The Discovery of Potential SARS-CoV-2 Natural Inhibitors among 4924 African Metabolites Targeting the Papain-like Protease: A Multi-Phase In Silico Approach. Metabolites, 12(11), 1122. https://doi.org/10.3390/metabo12111122
   PubMed Web of Science ®Google Scholar
• Gao, C., Peng, Y. N., Wang, H. Z., Fang, S. L., Zhang, M., Zhao, Q., & Liu, J. (2019). Inhibition of Heat Shock Protein 90 as a Novel Platform for the Treatment of Cancer. Current Pharmaceutical Design, 25(8), 849–855. https://doi.org/10.2174/1381612825666190503145944
   PubMed Web of Science ®Google Scholar
• Gao, T., Gu, G., Tian, J., Zhang, R., Zheng, X., Wang, Y., Pang, Q., & Liu, Q. (2017). LncRNA HSP90AA1-IT1 promotes gliomas by targeting miR-885-5p-CDK2 pathway. Oncotarget, 8(43), 75284–75297. https://doi.org/10.18632/oncotarget.20777
   PubMedGoogle Scholar
• Geiger, T. R., & Peeper, D. S. (2009). Metastasis mechanisms. Biochimica et Biophysica Acta, 1796(2), 293–308. https://doi.org/10.1016/j.bbcan.2009.07.006
   PubMed Web of Science ®Google Scholar
• Gogat, K., Le Gat, L., Van Den Berghe, L., Marchant, D., Kobetz, A., Gadin, S., Gasser, B., Quéré, I., Abitbol, M., & Menasche, M. (2004). VEGF and KDR gene expression during human embryonic and fetal eye development. Investigative Ophthalmology & Visual Science, 45(1), 7–14. https://doi.org/10.1167/iovs.02-1096
   PubMed Web of Science ®Google Scholar
• Griss, J., Viteri, G., Sidiropoulos, K., Nguyen, V., Fabregat, A., & Hermjakob, H. (2020). ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis. Mol Cell Proteomics, 19(12), 2115–2125. https://doi.org/10.1074/mcp.TIR120.002155
   PubMed Web of Science ®Google Scholar
• Guo, Y., Wang, J., Zhou, K., Lv, J., Wang, L., Gao, S., Keller, E. T., Zhang, Z. S., Wang, Q., & Yao, Z. (2020). Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC. FASEB Journal : official Publication of the Federation of American Societies for Experimental Biology, 34(6), 7927–7940. https://doi.org/10.1096/fj.201903266RR
   PubMed Web of Science ®Google Scholar
• Harari, D., & Yarden, Y. (2000). Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene, 19(53), 6102–6114. https://doi.org/10.1038/sj.onc.1203973
   PubMed Web of Science ®Google Scholar
• Harrold, J. M., Ramanathan, M., & Mager, D. E. (2013). Network-based approaches in drug discovery and early development. Clinical Pharmacology and Therapeutics, 94(6), 651–658. https://doi.org/10.1038/clpt.2013.176
   PubMed Web of Science ®Google Scholar
• Hiratsuka, S., Nakamura, K., Iwai, S., Murakami, M., Itoh, T., Kijima, H., Shipley, J. M., Senior, R. M., & Shibuya, M. (2002). MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell, 2(4), 289–300. https://doi.org/10.1016/s1535-6108(02)00153-8
   PubMed Web of Science ®Google Scholar
• Hsu, I., Vitkus, S., Da, J., & Yeh, S. (2013). Role of oestrogen receptors in bladder cancer development. Nature Reviews. Urology, 10(6), 317–326. https://doi.org/10.1038/nrurol.2013.53
   PubMed Web of Science ®Google Scholar
• Huang, Z., Wang, G., Wu, Y., Yang, T., Shao, L., Yang, B., Li, P., & Li, J. (2023). N6-methyladenosine-related lncRNAs in combination with computational histopathology and radiomics predict the prognosis of bladder cancer. Translational Oncology, 27, 101581. https://doi.org/10.1016/j.tranon.2022.101581
   PubMed Web of Science ®Google Scholar
• Johnson, E., Seachrist, D. D., DeLeon-Rodriguez, C. M., Lozada, K. L., Miedler, J., Abdul-Karim, F. W., & Keri, R. A. (2010). HER2/ErbB2-induced breast cancer cell migration and invasion require p120 catenin activation of Rac1 and Cdc42. The Journal of Biological Chemistry, 285(38), 29491–29501. https://doi.org/10.1074/jbc.M110.136770
   PubMed Web of Science ®Google Scholar
• Kadavakollu, S., Stailey, C., Kunapareddy, C. S., & White, S. (2014). Clotrimazole as a Cancer Drug: A Short Review. Medicinal Chemistry, 4(11), 722–724. https://doi.org/10.4172/2161-0444.1000219
   Google Scholar
• Kanehisa, M., & Goto, S. (2000). KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research, 28(1), 27–30. https://doi.org/10.1093/nar/28.1.27
   PubMed Web of Science ®Google Scholar
• Khan, Z., Nath, N., Rauf, A., Emran, T. B., Mitra, S., Islam, F., Chandran, D., Barua, J., Khandaker, M. U., Idris, A. M., Wilairatana, P., & Thiruvengadam, M. (2022). Multifunctional roles and pharmacological potential of β-sitosterol: Emerging evidence toward clinical applications. Chemico-Biological Interactions, 365, 110117. https://doi.org/10.1016/j.cbi.2022.110117
   PubMed Web of Science ®Google Scholar
• Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., & Bolton, E. E. (2021). PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Research, 49(D1), D1388–D1395. https://doi.org/10.1093/nar/gkaa971
   PubMed Web of Science ®Google Scholar
• Koshkin, V. S., O’Donnell, P., Yu, E. Y., & Grivas, P. (2019). Systematic Review: Targeting HER2 in Bladder Cancer. Bladder Cancer, 5(1), 1–12. https://doi.org/10.3233/BLC-180196
   Web of Science ®Google Scholar
• Lai, K., Killingsworth, M. C., & Lee, C. S. (2015). Gene of the month: PIK3CA. Journal of Clinical Pathology, 68(4), 253–257. https://doi.org/10.1136/jclinpath-2015-202885
   PubMed Web of Science ®Google Scholar
• Loaiza-Bonilla, A., Jensen, C. E., Shroff, S., Furth, E., Bonilla-Reyes, P. A., Deik, A. F., & Morrissette, J. (2016). KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer. Cureus, 8(2), e478. https://doi.org/10.7759/cureus.478
   PubMedGoogle Scholar
• Ma, J., Sawai, H., Ochi, N., Matsuo, Y., Xu, D., Yasuda, A., Takahashi, H., Wakasugi, T., & Takeyama, H. (2009). PTEN regulates angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells. Molecular and Cellular Biochemistry, 331(1-2), 161–171. https://doi.org/10.1007/s11010-009-0154-x
   PubMed Web of Science ®Google Scholar
• Ma, L., Lei, Q., & Su, Q. (2020). Network pharmacology approach to determine active compounds and potential targets associated with the anti-abortion effects of scutellariae radix. World Journal of Traditional Chinese Medicine, 6(3), 341–352. J. W. J. o. T. C. M https://doi.org/10.4103/wjtcm.wjtcm_35_20
   Google Scholar
• Madsen, C. D., & Sahai, E. (2010). Cancer dissemination–lessons from leukocytes. Developmental Cell, 19(1), 13–26. https://doi.org/10.1016/j.devcel.2010.06.013
   PubMed Web of Science ®Google Scholar
• Mallapur, S., Biradar, P. R., Kavatagimath, S. A., Patil, P., Patil, V., & Kudatarkar, N. (2021). Pharmacological Evaluation of Caesalpinia pulcherrima Leaf Extract for Anticancer Activity against Ehrlich Ascites Carcinoma Bearing Mice. Indian Journal of Pharmaceutical Education and Research, 55(1), 164–173. https://doi.org/10.5530/ijper.55.1.18
   Web of Science ®Google Scholar
• Martin-Way, D., Puche-Sanz, I., Cozar, J. M., Zafra-Gomez, A., Gomez-Regalado, M. D. C., Morales-Alvarez, C. M., Hernandez, A. F., Martinez-Gonzalez, L. J., & Alvarez-Cubero, M. J. (2022). Genetic variants of antioxidant enzymes and environmental exposures as molecular biomarkers associated with the risk and aggressiveness of bladder cancer. The Science of the Total Environment, 843, 156965. https://doi.org/10.1016/j.scitotenv.2022.156965
   PubMed Web of Science ®Google Scholar
• Mazumdar, A., Wang, R. A., Mishra, S. K., Adam, L., Bagheri-Yarmand, R., Mandal, M., Vadlamudi, R. K., Kumar, R &., others. (2001). Transcriptional repression of oestrogen receptor by metastasis-associated protein1 corepressor. Nature Cell Biology, 3(1), 30–37. https://doi.org/10.1038/35050532
   PubMed Web of Science ®Google Scholar
• Meyer, E. A., Castellano, R. K., & Diederich, F. (2003). Interactions with aromatic rings in chemical and biological recognition. Angewandte Chemie (International ed. in English), 42(11), 1210–1250. https://doi.org/10.1002/anie.200390319
   PubMed Web of Science ®Google Scholar
• Morgia, G., Falsaperla, M., Malaponte, G., Madonia, M., Indelicato, M., Travali, S., & Mazzarino, M. C. (2005). Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer. Urological Research, 33(1), 44–50. https://doi.org/10.1007/s00240-004-0440-8
   PubMedGoogle Scholar
• Nishida, N., Yano, H., Nishida, T., Kamura, T., & Kojiro, M. (2006). Angiogenesis in cancer. Vascular Health and Risk Management, 2(3), 213–219. https://doi.org/10.2147/vhrm.2006.2.3.213
   PubMedGoogle Scholar
• Nutt, J. E., Durkan, G. C., Mellon, J. K., & Lunec, J. (2003). Matrix metalloproteinases (MMPs) in bladder cancer: The induction of MMP9 by epidermal growth factor and its detection in urine. BJU International, 91(1), 99–104. https://doi.org/10.1046/j.1464-410x.2003.04020.x
   PubMed Web of Science ®Google Scholar
• Pagès, H., Carlson, M., Falcon, S., & Li, N. (2022). AnnotationDbi: Manipulation of SQLite-based annotations in Bioconductor. R Package Version, 1, 58–58.
   Google Scholar
• Páll, S., Abraham, M. J., Kutzner, C., Hess, B., & Lindahl, E. (2015). Tackling Exascale Software Challenges in Molecular Dynamics Simulations with GROMACS [Paper presentation]. Paper presented at The Solving Software Challenges for Exascale, 2015//), Cham.
   Google Scholar
• Pereira, I. T., Ramos, E. A. S., Costa, E. T., Camargo, A. A., Manica, G. C. M., Klassen, L. M. B., Chequin, A., Braun-Prado, K., Pedrosa, F. d O., Souza, E. M., Costa, F. F., & Klassen, G. (2014). Fibronectin affects transient MMP2 gene expression through DNA demethylation changes in non-invasive breast cancer cell lines. PloS One, 9(9), e105806. https://doi.org/10.1371/journal.pone.0105806
   PubMed Web of Science ®Google Scholar
• Qin, L., Liao, L., Redmond, A., Young, L., Yuan, Y., Chen, H., O'Malley, B. W., & Xu, J. (2008). The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression. Molecular and Cellular Biology, 28(19), 5937–5950. https://doi.org/10.1128/MCB.00579-08
   PubMed Web of Science ®Google Scholar
• Révillion, F., Bonneterre, J., & Peyrat, J. P. (1998). ERBB2 oncogene in human breast cancer and its clinical significance. European Journal of Cancer (Oxford, England : 1990), 34(6), 791–808. https://doi.org/10.1016/s0959-8049(97)10157-5
   PubMed Web of Science ®Google Scholar
• Safran, M., Rosen, N., Twik, M., BarShir, R., Stein, I., T., Dahary, D. F. S., & Lancet, D. (2022). The GeneCards Suite. In I. Abugessaisa & T. Kasukawa (Eds.). Singapore. Practical Guide to Life Science Databases. Springer.
   Google Scholar
• Saha Roy, S., & Vadlamudi, R. K. (2012). Role of estrogen receptor signaling in breast cancer metastasis. International Journal of Breast Cancer, 2012, 1–8. https://doi.org/10.1155/2012/654698
   Google Scholar
• Sakle, N. S., Lokwani, D., & Mokale, S. N. (2019). Caesalpinia pulcherrima arrests cell cycle and triggers reactive oxygen species-induced mitochondrial-mediated apoptosis and necroptosis via modulating estrogen and estrogen receptors. Pharmacognosy Magazine, 15(64), 288–288. https://doi.org/10.4103/pm.pm_100_19
   Web of Science ®Google Scholar
• Sayers, E. W., Bolton, E. E., Brister, J. R., Canese, K., Chan, J., Comeau, D. C., Connor, R., Funk, K., Kelly, C., Kim, S., Madej, T., Marchler-Bauer, A., Lanczycki, C., Lathrop, S., Lu, Z., Thibaud-Nissen, F., Murphy, T., Phan, L., Skripchenko, Y., … Sherry, S. T. (2022). Database resources of the national center for biotechnology information. Nucleic Acids Research, 50(D1), D20–D26. &. https://doi.org/10.1093/nar/gkab1112
   PubMed Web of Science ®Google Scholar
• Shen, C. Y., Lee, C. F., Chou, W. T., Hwang, J. J., Tyan, Y. S., & Chuang, H. Y. (2022). Liposomal β-Sitosterol Suppresses Metastasis of CT26/luc Colon Carcinoma via Inhibition of MMP-9 and Evoke of Immune System. Pharmaceutics, 14(6), 1214. https://doi.org/10.3390/pharmaceutics14061214
   PubMed Web of Science ®Google Scholar
• Strell, C., & Entschladen, F. (2008). Extravasation of leukocytes in comparison to tumor cells. Cell Communication and Signaling : CCS, 6, 10–10. https://doi.org/10.1186/1478-811X-6-10
   PubMedGoogle Scholar
• Strickler, J. H., Yoshino, T., Graham, R. P., Siena, S., & Bekaii-Saab, T. (2022). Diagnosis and Treatment of ERBB2-Positive Metastatic Colorectal Cancer: A Review. JAMA Oncology, 8(5), 760–769. https://doi.org/10.1001/jamaoncol.2021.8196
   PubMed Web of Science ®Google Scholar
• Su, Z., Yang, Z., Xu, Y., Chen, Y., & Yu, Q. (2015). Apoptosis, autophagy, necroptosis and cancer metastasis. Molecular Cancer, 14, 48–48. https://doi.org/10.1186/s12943-015-0321-5
   PubMed Web of Science ®Google Scholar
• Sukawa, Y., Yamamoto, H., Nosho, K., Ito, M., Igarashi, H., Naito, T., Mitsuhashi, K., Matsunaga, Y., Takahashi, T., Mikami, M., Adachi, Y., Suzuki, H., & Shinomura, Y. (2014). HER2 expression and PI3K-Akt pathway alterations in gastric cancer. Digestion, 89(1), 12–17. https://doi.org/10.1159/000356201
   PubMed Web of Science ®Google Scholar
• Takahashi, Y., Cleary, K. R., Mai, M., Kitadai, Y., Bucana, C. D., & Ellis, L. M. (1996). Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer. Clin Cancer Res, 2(10), 1679–1684.
   PubMed Web of Science ®Google Scholar
• Tan, H. D., Leong, H. J. Y., Yap, W. H., Chia, A. Y. Y., & Tang, Y. Q. (2022). Network Analysis in the Identification of Genes Conferring Metastatic Potential in Hepatocellular Carcinoma. Eurasian Journal of Medicine and Oncology, 6(4), 364–380. https://doi.org/10.14744/ejmo.2022.37552
   Google Scholar
• Team, B. C. (2015). Homo.sapiens: Annotation package for the Homo.sapiens object. R Package Version, 1(3), 1–1.
   Google Scholar
• Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., & Mackerell, A. D. Jr (2010). CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. Journal of Computational Chemistry, 31(4), 671–690. https://doi.org/10.1002/jcc.21367
   PubMed Web of Science ®Google Scholar
• Wang, X., Bove, A. M., Simone, G., & Ma, B. (2020). Molecular Bases of VEGFR-2-Mediated Physiological Function and Pathological Role. Frontiers in Cell and Developmental Biology, 8, 599281. https://doi.org/10.3389/fcell.2020.599281
   PubMed Web of Science ®Google Scholar
• Wickham, H., Averick, M., Bryan, J., Chang, W., McGowan, L. D., Francois, R., Grolemund, G., Hayes, A., Henry, L., Hester, J., Kuhn, M., Pedersen, T. L., Miller, E., Bache, S. M., Muller, K., Ooms, J., Robinson, D., Seidel, D. P., Spinu, V., … Yutani, H. (2019). Welcome to the tidyverse. Journal of Open Source Software, 4(43), 1686–1686. https://doi.org/10.21105/joss.01686
   Google Scholar
• Workman, P., Burrows, F., Neckers, L., & Rosen, N. (2007). Drugging the Cancer Chaperone HSP90: Combinatorial Therapeutic Exploitation of Oncogene Addiction and Tumor Stress. Annals of the New York Academy of Sciences, 1113, 202–216. https://doi.org/10.1196/annals.1391.012
   PubMed Web of Science ®Google Scholar
• World Health Organization. (2013). WHO traditional medicine strategy: 2014-2023. :
   Google Scholar
• Wu, C., Yu, Q., Shou, W., Zhang, K., Li, Y., Guo, W., & Bao, Q. (2022). Identification of molecular mechanism of the anti-lung cancer effect of Jin Ning Fang using network pharmacology and its experimental verification. All Life, 15(1), 745–759. https://doi.org/10.1080/26895293.2022.2085813
   Web of Science ®Google Scholar
• Wu, T., Hu, E., Xu, S., Chen, M., Guo, P., Dai, Z., Feng, T., Zhou, L., Tang, W., Zhan, L., Fu, X., Liu, S., Bo, X., & Yu, G. (2021). clusterProfiler 4.0 A universal enrichment tool for interpreting omics data. Innovation (Cambridge (Mass.)), 2(3), 100141. https://doi.org/10.1016/j.xinn.2021.100141
   Google Scholar
• Xia, Q. D., Xun, Y., Lu, J. L., Lu, Y. C., Yang, Y. Y., Zhou, P., Hu, J., Li, C., & Wang, S. G. (2020). Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID?19. Cell Proliferation, 53(12), e12949. https://doi.org/10.1111/cpr.12949
   Web of Science ®Google Scholar
• Xiang, X., You, X. M., & Li, L. Q. (2018). Expression of HSP90AA1/HSPA8 in hepatocellular carcinoma patients with depression. OncoTargets and Therapy, 11, 3013–3023. https://doi.org/10.2147/ott.S159432
   PubMed Web of Science ®Google Scholar
• Xiao, X., Wang, W., Li, X., Li, Y., Yang, D., Shen, C., Gao, P., Wu, J., Guo, S., & Guo, Z. (2018). MicroRNA-495 suppresses osteosarcoma invasion and migration by targeting HSP90AA1.
   Google Scholar
• Xu, B., Bai, Z., Yin, J., & Zhang, Z. (2019). Global transcriptomic analysis identifies SERPINE1 as a prognostic biomarker associated with epithelial-to-mesenchymal transition in gastric cancer. PeerJ. 7, e7091. https://doi.org/10.7717/peerj.7091
   PubMed Web of Science ®Google Scholar
• Xue, Q., Cao, L., Chen, X. Y., Zhao, J., Gao, L., Li, S. Z., & Fei, Z. (2017). High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates. Oncology Letters, 13(3), 1325–1330. https://doi.org/10.3892/ol.2017.5567
   PubMed Web of Science ®Google Scholar
• Yow, H. Y., & Tang, Y. Q. (2022). Computational Screening of Repurposed Drugs Targeting Sars-Cov-2 Main Protease By Molecular Docking. Sudan Journal of Medical Sciences, 17(3), 387–400. https://doi.org/10.18502/sjms.v17i3.12125
   Web of Science ®Google Scholar
• Yu, W., He, X., Vanommeslaeghe, K., & MacKerell, A. D. (2012). Extension of the CHARMM General Force Field to sulfonyl-containing compounds and its utility in biomolecular simulations. Journal of Computational Chemistry, 33(31), 2451–2468. https://doi.org/10.1002/jcc.23067
   PubMed Web of Science ®Google Scholar
• Yuan, H., Ma, Q., Cui, H., Liu, G., Zhao, X., Li, W., & Piao, G. (2017). How Can Synergism of Traditional Medicines Benefit from Network Pharmacology? Molecules, 22(7), 1135. https://doi.org/10.3390/molecules22071135
   PubMed Web of Science ®Google Scholar
• Zhang, W., Liu, A., Li, Y., Zhao, X., Lv, S., Zhu, W., & Jin, Y. (2012). Anticancer activity and mechanism of juglone on human cervical carcinoma HeLa cells. Canadian Journal of Physiology and Pharmacology, 90(11), 1553–1558. https://doi.org/10.1139/y2012-134
   PubMed Web of Science ®Google Scholar
• Zhang, X., Chen, H., Lin, H., Wen, R., & Yang, F. (2022). High-Throughput Screening and Molecular Dynamics Simulation of Natural Products for the Identification of Anticancer Agents against MCM7 Protein. Applied Bionics and Biomechanics, 2022, 8308192. https://doi.org/10.1155/2022/8308192
   PubMed Web of Science ®Google Scholar
• Zhao, Q., Zheng, B., Feng, P., & Li, X. (2021). A Study to Decipher the Potential Effects of Butylphthalide against Central Nervous System Diseases Based on Network Pharmacology and Molecular Docking Integration Strategy. Evidence-Based Complementary and Alternative Medicine : eCAM, 2021, 6694698. https://doi.org/10.1155/2021/6694698
   PubMed Web of Science ®Google Scholar
• Zhao, S., & Iyengar, R. (2012). Systems pharmacology: Network analysis to identify multiscale mechanisms of drug action. Annual Review of Pharmacology and Toxicology, 52, 505–521. https://doi.org/10.1146/annurev-pharmtox-010611-134520
   PubMed Web of Science ®Google Scholar
• Zheng, S., Huang, J., Zhou, K., Zhang, C., Xiang, Q., Tan, Z., Wang, T., & Fu, X. (2011). 17β-Estradiol Enhances Breast Cancer Cell Motility and Invasion via Extra-Nuclear Activation of Actin-Binding Protein Ezrin, 6, 7–7.
   Google Scholar