Clinical Efficacy of Vaccaria segetalis Seeds and Gleditsia sinensis Lam Thorns on Prostate Cancer: A Preliminary Mechanism Analysis based on Network Pharmacology

Page: [1874 - 1885] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

Objective: The mechanism of Vaccaria segetalis (VS) seeds and Gleditsia sinensis Lam (GS) thorns in the treatment of prostate cancer (PC) was analyzed via network pharmacological analysis methods and molecular docking.

Methods: The Traditional Chinese Medicine Systems Pharmacology Database Platform (TCMSP) was used to screen the PC’s effective components and targets; GeneCards and OMIM databases to search for targets related to PC. The intersection target was uploaded to the STRING database to obtain a proteinprotein interaction (PPI) network; and the key targets were screened from the PPI network via R language, CytoNCA, and CytoHubba tools. Gene Ontology (GO) and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment tools were used to analyze biological processes and molecular docking of key targets via AutoDock Vina software.

Results: A total of 13 compounds, 229 nodes, 879 edges, and 20 key targets were obtained through the PPI network. Go and KEGG analysis showed that the intersection targets of VS and GS with PC were mainly involved in regulating cell promotion, cell apoptosis, cell cycle, and reversing epithelialmesenchymal transition (EMT) processing. Molecular docking revealed that the relevant targets of potential PC were characterized with stabilized affinity. Specifically, the targets with better affinity included estrogen receptor 1 (ESR1) with kaempferol, transcription factor p65 (RELA) with fisetin, kaempferol, quercetin, and mitogen-activated protein kinase 1 (MAPK1) with fisetin, and G1/S-specific cyclin-D1 (CCND1) with fisetin, kaempferol, and quercetin.

Conclusion: In summary, this study reveals potential molecular therapeutic mechanisms of VS and GS in PC and provides a reference for the wide application of VS and GS in the clinical management of PC.

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Culp, M.B.; Soerjomataram, I.; Efstathiou, J.A.; Bray, F.; Jemal, A. Recent global patterns in prostate cancer incidence and mortality rates. Eur. Urol., 2020, 77(1), 38-52.
[http://dx.doi.org/10.1016/j.eururo.2019.08.005] [PMID: 31493960]
[3]
Ho, V.W.T.; Tan, H.Y.; Guo, W.; Li, S.; Wang, N.; Meng, W.; So, T.; Yu, E.C.L.; Feng, Y. Efficacy and safety of chinese herbal medicine on treatment of breast cancer: A meta-analysis of randomized controlled trials. Am. J. Chin. Med., 2021, 49(7), 1557-1575.
[http://dx.doi.org/10.1142/S0192415X21500737] [PMID: 34530698]
[4]
Liu, J.M.; Lin, P.H.; Hsu, R.J.; Chang, Y.H.; Cheng, K.C.; Pang, S.T.; Lin, S.K. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer. Medicine, 2016, 95(31), e4475.
[http://dx.doi.org/10.1097/MD.0000000000004475] [PMID: 27495088]
[5]
Gucalp, A.; Iyengar, N.M.; Zhou, X.K.; Giri, D.D.; Falcone, D.J.; Wang, H.; Williams, S.; Krasne, M.D.; Yaghnam, I.; Kunzel, B.; Morris, P.G.; Jones, L.W.; Pollak, M.; Laudone, V.P.; Hudis, C.A.; Scher, H.I.; Scardino, P.T.; Eastham, J.A.; Dannenberg, A.J. Periprostatic adipose inflammation is associated with high-grade prostate cancer. Prostate Cancer Prostat Dis., 2017, 20(4), 418-423.
[http://dx.doi.org/10.1038/pcan.2017.31] [PMID: 28653675]
[6]
Roumiguié, M.; Estève, D.; Manceau, C.; Toulet, A.; Gilleron, J.; Belles, C.; Jia, Y.; Houël, C.; Pericart, S.; LeGonidec, S.; Valet, P.; Cormont, M.; Tanti, J.F.; Malavaud, B.; Bouloumié, A.; Milhas, D.; Muller, C. Periprostatic adipose tissue displays a chronic hypoxic state that limits its expandability. Am. J. Pathol., 2022, 192(6), 926-942.
[http://dx.doi.org/10.1016/j.ajpath.2022.03.008] [PMID: 35358473]
[7]
Fontaine, A.; Bellanger, D.; Guibon, R.; Bruyère, F.; Brisson, L.; Fromont, G. Lipophagy and prostate cancer: Association with disease aggressiveness and proximity to periprostatic adipose tissue. J. Pathol., 2021, 255(2), 166-176.
[http://dx.doi.org/10.1002/path.5754] [PMID: 34219239]
[8]
Shen, Z.J.; Cheng, H.B.; Shen, W.X.; Wu, M.H. Correlation between tumor inflammatory microenvironment and “cancerous toxin” pathogenesis. J. Beijing Univ. Trad. Chinese Med., 2015, 38(01), 14-17.
[9]
Cheng, H.B.; Zhou, Z.Y. Modern Interpretation of the Scientific Connotation of the Pathogenesis of Cancerous Toxin. J. Nanjing Univ. Trad. Chinese Med., 2021, 37(05), 637-641.
[10]
Wang, L.; Cui, D.; Wang, X.; Zhang, J.; Yang, Z.; Qin, Z.; Cui, D.; Kong, X.; Wang, X.; Li, J. Analgesic and anti-inflammatory effects of hydroalcoholic extract isolated from Semen vaccariae. Pak. J. Pharm. Sci., 2015, 28(3)(Suppl.), 1043-1048.
[PMID: 26051722]
[11]
Tian, M.; Huang, Y.; Wang, X.; Cao, M.; Zhao, Z.; Chen, T.; Yuan, C.; Wang, N.; Zhang, B.; Li, C.; Zhou, X. Vaccaria segetalis: A review of ethnomedicinal, phytochemical, pharmacological, and toxicological findings. Front Chem., 2021, 9, 666280.
[http://dx.doi.org/10.3389/fchem.2021.666280] [PMID: 33996757]
[12]
Xu, F.; Liu, Y.; Zhu, X.; Li, S.; Shi, X.; Li, Z.; Ai, M.; Sun, J.; Hou, B.; Cai, W.; Sun, H.; Ni, L.; Zhou, Y.; Qiu, L. Protective effects and mechanisms of vaccarin on vascular endothelial dysfunction in diabetic angiopathy. Int. J. Mol. Sci., 2019, 20(18), 4587.
[http://dx.doi.org/10.3390/ijms20184587] [PMID: 31533227]
[13]
Zhang, J.P.; Tian, X.H.; Yang, Y.X.; Liu, Q.X.; Wang, Q.; Chen, L.P.; Li, H.L.; Zhang, W.D. Gleditsia species: An ethnomedical, phytochemical and pharmacological review. J. Ethnopharmacol., 2016, 178, 155-171.
[http://dx.doi.org/10.1016/j.jep.2015.11.044] [PMID: 26643065]
[14]
Ryu, S.; Park, K.; Lee, S. Gleditsia sinensis thorn attenuates the collagen-based migration of PC3 prostate cancer cells through the suppression of α2β1 integrin expression. Int. J. Mol. Sci., 2016, 17(3), 328.
[http://dx.doi.org/10.3390/ijms17030328] [PMID: 26950116]
[15]
Mou, R.Y.; Li, X.J.; Chen, T.Q.; Liu, Z.; Wang, C.Y.; Liu, J.C.; Jia, Y.J. Study on the mechanism of Vaccariae semen in the treatment of prostate cancer based on network pharmacology. World J. Integrat. Trad. Western Med., 2021, 16(5), 785-792.
[16]
Yang, Q.; Fan, Z. Potential Mechanisms of Er Chen Decoction against polycystic ovary syndrome based on network pharmacology strategy. J. Biol. Reg. Homeo. Agent., 2022, 36(5), 1489-1499.
[17]
Gao, J.; Yang, S.; Xie, G.; Pan, J.; Zhu, F. Integrating network pharmacology and experimental verification to explore the pharmacological mechanisms of aloin against gastric cancer. Drug Des. Devel. Ther., 2022, 16, 1947-1961.
[http://dx.doi.org/10.2147/DDDT.S360790] [PMID: 35757520]
[18]
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.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[19]
Zhang, W.; Xue, K.; Gao, Y.; Huai, Y.; Wang, W.; Miao, Z.; Dang, K.; Jiang, S.; Qian, A. Systems pharmacology dissection of action mechanisms of Dipsaci Radix for osteoporosis. Life Sci., 2019, 235, 116820.
[http://dx.doi.org/10.1016/j.lfs.2019.116820] [PMID: 31476308]
[20]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[21]
Tang, Y.; Li, M.; Wang, J.; Pan, Y.; Wu, F.X. CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems, 2015, 127, 67-72.
[http://dx.doi.org/10.1016/j.biosystems.2014.11.005] [PMID: 25451770]
[22]
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(Suppl. 4), S11.
[23]
Sherman, B.T.; Hao, M.; Qiu, J.; Jiao, X.; Baseler, M.W.; Lane, H.C.; Imamichi, T.; Chang, W. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res., 2022, 50(W1), W216-W221.
[http://dx.doi.org/10.1093/nar/gkac194] [PMID: 35325185]
[24]
Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[25]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[26]
AlZaim, I.; Al-Saidi, A.; Hammoud, S.H.; Darwiche, N.; Al-Dhaheri, Y.; Eid, A.H.; El-Yazbi, A.F. Thromboinflammatory processes at the nexus of metabolic dysfunction and prostate cancer: The emerging role of periprostatic adipose tissue. Cancers, 2022, 14(7), 1679.
[http://dx.doi.org/10.3390/cancers14071679] [PMID: 35406450]
[27]
Gao, J.; Yang, X.; Yin, W. From traditional usage to pharmacological evidence: A systematic mini-review of Spina Gleditsiae. Evid. Based Complement. Alternat. Med., 2016, 2016, 3898957.
[http://dx.doi.org/10.1155/2016/3898957] [PMID: 27433183]
[28]
Yang, X.Y.; Li, Z.L.; Pu, S.B.; Qian, S.H. Research advances on the spines of Gleditsia sinensis Lam. Zhongguo Yesheng Zhiwu Ziyuan, 2015, 34(13), 38-41.
[29]
Ponte, L.G.S.; Pavan, I.C.B.; Mancini, M.C.S.; da Silva, L.G.S.; Morelli, A.P.; Severino, M.B.; Bezerra, R.M.N.; Simabuco, F.M. The hallmarks of flavonoids in cancer. Molecules, 2021, 26(7), 2029.
[http://dx.doi.org/10.3390/molecules26072029] [PMID: 33918290]
[30]
Forni, C.; Rossi, M.; Borromeo, I.; Feriotto, G.; Platamone, G.; Tabolacci, C.; Mischiati, C.; Beninati, S. Flavonoids: A Myth or a Reality for Cancer Therapy? Molecules, 2021, 26(12), 3583.
[http://dx.doi.org/10.3390/molecules26123583] [PMID: 34208196]
[31]
Kashyap, D.; Garg, V.K.; Tuli, H.S.; Yerer, M.B.; Sak, K.; Sharma, A.K.; Kumar, M.; Aggarwal, V.; Sandhu, S.S. Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential. Biomolecules, 2019, 9(5), 174.
[http://dx.doi.org/10.3390/biom9050174] [PMID: 31064104]
[32]
Crocetto, F.; di Zazzo, E.; Buonerba, C.; Aveta, A.; Pandolfo, S.D.; Barone, B.; Trama, F.; Caputo, V.F.; Scafuri, L.; Ferro, M.; Cosimato, V.; Fusco, F.; Imbimbo, C.; Di Lorenzo, G. Kaempferol, Myricetin and Fisetin in prostate and bladder cancer: A systematic review of the literature. Nutrients, 2021, 13(11), 3750.
[http://dx.doi.org/10.3390/nu13113750] [PMID: 34836005]
[33]
Khan, N.; Asim, M.; Afaq, F.; Abu Zaid, M.; Mukhtar, H. A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic nude mice. Cancer Res., 2008, 68(20), 8555-8563.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0240] [PMID: 18922931]
[34]
Yang, F.; Song, L.; Wang, H.; Wang, J.; Xu, Z.; Xing, N. Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential. (Review). Oncol. Rep., 2015, 33(6), 2659-2668.
[http://dx.doi.org/10.3892/or.2015.3886] [PMID: 25845380]
[35]
Ward, A.B.; Mir, H.; Kapur, N.; Gales, D.N.; Carriere, P.P.; Singh, S. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J. Surg. Oncol., 2018, 16(1), 108.
[http://dx.doi.org/10.1186/s12957-018-1400-z] [PMID: 29898731]
[36]
Da, J.; Xu, M.; Wang, Y.; Li, W.; Lu, M.; Wang, Z. Kaempferol promotes apoptosis while inhibiting cell proliferation via androgen-dependent pathway and suppressing vasculogenic mimicry and invasion in prostate cancer. Anal. Cell. Pathol. (Amst.), 2019, 2019, 1907698.
[http://dx.doi.org/10.1155/2019/1907698] [PMID: 31871879]
[37]
Liu, G.; Zhang, J.; Frey, L.; Gang, X.; Wu, K.; Liu, Q.; Lilly, M.; Wu, J. Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue. J. Hematol. Oncol., 2017, 10(1), 14.
[http://dx.doi.org/10.1186/s13045-016-0386-7] [PMID: 28077171]
[38]
Shan, B.; Gerez, J.; Haedo, M.; Fuertes, M.; Theodoropoulou, M.; Buchfelder, M.; Losa, M.; Stalla, G.K.; Arzt, E.; Renner, U. RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells. Endocr. Relat. Cancer, 2012, 19(1), 13-27.
[http://dx.doi.org/10.1530/ERC-11-0211] [PMID: 22009797]
[39]
Chandra, P.; Rajaram, P.; Ticku, S.; Pallavi, B.K.; Rudresh, K.B.; Mansabdar, P. Epidermal growth factor receptor: Role in human cancer. Indian J. Dent. Res., 2017, 28(6), 687-694.
[http://dx.doi.org/10.4103/ijdr.IJDR_534_16] [PMID: 29256471]
[40]
Qie, S.; Diehl, J.A. Cyclin D1, cancer progression, and opportunities in cancer treatment. J. Mol. Med. , 2016, 94(12), 1313-1326.
[http://dx.doi.org/10.1007/s00109-016-1475-3] [PMID: 27695879]
[41]
Roudsari, N.M.; Lashgari, N.A.; Momtaz, S.; Abaft, S.; Jamali, F.; Safaiepour, P.; Narimisa, K.; Jackson, G.; Bishayee, A.; Rezaei, N.; Abdolghaffari, A.H.; Bishayee, A. Inhibitors of the PI3K/Akt/mTOR pathway in prostate cancer chemoprevention and intervention. Pharmaceutics, 2021, 13(8), 1195.
[http://dx.doi.org/10.3390/pharmaceutics13081195] [PMID: 34452154]
[42]
Zhu, W.; Shao, Y.; Yang, M.; Jia, M.; Peng, Y. Asparaginyl endopeptidase promotes proliferation and invasiveness of prostate cancer cells via PI3K/AKT signaling pathway. Gene, 2016, 594(2), 176-182.
[http://dx.doi.org/10.1016/j.gene.2016.08.049] [PMID: 27590439]
[43]
Yan, G.; Ru, Y.; Wu, K.; Yan, F.; Wang, Q.; Wang, J.; Pan, T.; Zhang, M.; Han, H.; Li, X.; Zou, L. GOLM1 promotes prostate cancer progression through activating PI3K‐AKT‐mTOR signaling. Prostate, 2018, 78(3), 166-177.
[http://dx.doi.org/10.1002/pros.23461] [PMID: 29181846]
[44]
Niture, S.; Lin, M.; Odera, J.O.; Moore, J.; Zhe, H.; Chen, X.; Suy, S.; Collins, S.P.; Kumar, D. TNFAIP8 drives metabolic reprogramming to promote prostate cancer cell proliferation. Int. J. Biochem. Cell Biol., 2021, 130, 105885.
[http://dx.doi.org/10.1016/j.biocel.2020.105885] [PMID: 33227392]
[45]
Feng, Y.; Sun, C.; Zhang, L.; Wan, H.; Zhou, H.; Chen, Y.; Zhu, L.; Xia, G.; Mi, Y. Upregulation of COPB2 promotes prostate cancer proliferation and invasion through the MAPK/TGF-β signaling pathway. Front. Oncol., 2022, 12, 865317.
[http://dx.doi.org/10.3389/fonc.2022.865317] [PMID: 35600351]
[46]
Davis, J.E.; Xie, X.; Guo, J.; Huang, W.; Chu, W.M.; Huang, S.; Teng, Y.; Wu, G. ARF1 promotes prostate tumorigenesis via targeting oncogenic MAPK signaling. Oncotarget, 2016, 7(26), 39834-39845.
[http://dx.doi.org/10.18632/oncotarget.9405] [PMID: 27213581]
[47]
Chappell, W.H.; Abrams, S.L.; Lertpiriyapong, K.; Fitzgerald, T.L.; Martelli, A.M.; Cocco, L.; Rakus, D.; Gizak, A.; Terrian, D.; Steelman, L.S.; McCubrey, J.A. Novel roles of androgen receptor, epidermal growth factor receptor, TP53, regulatory RNAs, NF-kappa-B, chromosomal translocations, neutrophil associated gelatinase, and matrix metalloproteinase-9 in prostate cancer and prostate cancer stem cells. Adv. Biol. Regul., 2016, 60, 64-87.
[http://dx.doi.org/10.1016/j.jbior.2015.10.001] [PMID: 26525204]
[48]
Al Zoubi, M.; Otoum, R.; Alorjani, M.; Al Bashir, S. Al Trad, B.; Abualrja, M.; Al-Khatib, S.; Al-Batayneh, K. TP53, SPOP and PIK3CA Genes Status in Prostate Cancer. Asian Pac. J. Cancer Prev., 2020, 21(11), 3365-3371.
[http://dx.doi.org/10.31557/APJCP.2020.21.11.3365] [PMID: 33247697]
[49]
Dyson, N.J. RB1: A prototype tumor suppressor and an enigma. Genes Dev., 2016, 30(13), 1492-1502.
[http://dx.doi.org/10.1101/gad.282145.116] [PMID: 27401552]
[50]
Mishra, S.; Tai, Q.; Gu, X.; Schmitz, J.; Poullard, A.; Fajardo, R.J.; Mahalingam, D.; Chen, X.; Zhu, X.; Sun, L.Z. Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer. Oncotarget, 2015, 6(42), 44388-44402.
[http://dx.doi.org/10.18632/oncotarget.6317] [PMID: 26575018]
[51]
Thangavel, C.; Boopathi, E.; Liu, Y.; Haber, A.; Ertel, A.; Bhardwaj, A.; Addya, S.; Williams, N.; Ciment, S.J.; Cotzia, P.; Dean, J.L.; Snook, A.; McNair, C.; Price, M.; Hernandez, J.R.; Zhao, S.G.; Birbe, R.; McCarthy, J.B.; Turley, E.A.; Pienta, K.J.; Feng, F.Y.; Dicker, A.P.; Knudsen, K.E.; Den, R.B. RB loss promotes prostate cancer metastasis. Cancer Res., 2017, 77(4), 982-995.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1589] [PMID: 27923835]
[52]
Nastały, P.; Stoupiec, S.; Popęda, M.; Smentoch, J.; Schlomm, T.; Morrissey, C.; Żaczek, A.J.; Beyer, B.; Tennstedt, P.; Graefen, M.; Eltze, E.; Maiuri, P.; Semjonow, A.; Pantel, K.; Brandt, B.; Bednarz-Knoll, N. EGFR as a stable marker of prostate cancer dissemination to bones. Br. J. Cancer, 2020, 123(12), 1767-1774.
[http://dx.doi.org/10.1038/s41416-020-01052-8] [PMID: 32901137]
[53]
Odero-Marah, V.; Hawsawi, O.; Henderson, V.; Sweeney, J. Epithelial-Mesenchymal Transition (EMT) and prostate cancer. Adv. Exp. Med. Biol., 2018, 1095, 101-110.
[http://dx.doi.org/10.1007/978-3-319-95693-0_6] [PMID: 30229551]
[54]
Bhat, F.A.; Sharmila, G.; Balakrishnan, S.; Arunkumar, R.; Elumalai, P.; Suganya, S.; Raja Singh, P.; Srinivasan, N.; Arunakaran, J. Quercetin reverses EGF-induced epithelial to mesenchymal transition and invasiveness in prostate cancer (PC-3) cell line via EGFR/PI3K/Akt pathway. J. Nutr. Biochem., 2014, 25(11), 1132-1139.
[http://dx.doi.org/10.1016/j.jnutbio.2014.06.008] [PMID: 25150162]
[55]
Nguyen, D.P.; Li, J.; Tewari, A.K. Inflammation and prostate cancer: The role of interleukin 6 (IL-6). BJU Int., 2014, 113(6), 986-992.
[http://dx.doi.org/10.1111/bju.12452] [PMID: 24053309]
[56]
Witte, K.E.; Pfitzenmaier, J.; Storm, J.; Lütkemeyer, M.; Wimmer, C.; Schulten, W.; Czaniera, N.; Geisler, M.; Förster, C.; Wilkens, L.; Knabbe, C.; Mertzlufft, F.; Kaltschmidt, B. am Esch, J.S.; Kaltschmidt, C. Analysis of several pathways for efficient killing of prostate cancer stem cells: A central role of NF-κB RELA. Int. J. Mol. Sci., 2021, 22(16), 8901.
[http://dx.doi.org/10.3390/ijms22168901] [PMID: 34445612]