Network Pharmacology Insights into Broccoli Microgreens for Prostate Cancer
DOI:
https://doi.org/10.60084/hjas.v3i1.264Keywords:
Prostate cancer, Network pharmacology, Broccoli microgreens, Anticancer therapy, Bioactive compoundsAbstract
Prostate cancer is a leading malignancy in men, ranking fourth globally and fifth in Indonesia (GLOBOCAN 2020). Conventional therapies, though available, are limited by high costs, side effects, and resistance, highlighting the need for accessible alternatives. Broccoli microgreens, rich in bioactive compounds, have shown potential in preventing and treating various cancers. This study hypothesized that bioactive compounds in broccoli microgreens interact with molecular targets involved in prostate cancer progression. To test this hypothesis, we employed a network pharmacology-based in silico approach to systematically explore these interactions and identify potential therapeutic mechanisms. Bioactive compounds in broccoli microgreens were identified using liquid chromatography-mass spectrometry (LC-MS) and analyzed via the PubChem database. The biological activities of these compounds were predicted using PASS Online, focusing on their capacity to modulate TP53 gene expression. Pharmacokinetic and toxicity evaluations were performed using ADMETLab 3.0 and Protox 3.0 to assess their safety and drug-like properties. Target proteins were identified through SwissTargetPrediction and GeneCards, while protein-protein interaction networks were constructed using STRING. The pharmacological network was visualized using Cytoscape to elucidate the molecular mechanisms of action. The analysis identified 528 relevant target proteins, with key roles attributed to SRC and EGFR, both critical in resistance to EGFR tyrosine kinase inhibitors and in regulating processes such as cell proliferation, apoptosis resistance, and metastatic potential. Through network pharmacology, bioactive compounds such as kaempferol and polydatin were identified as potential inhibitors of these targets, demonstrating their ability to modulate pathways essential to prostate cancer progression. In conclusion, broccoli microgreens contain bioactive compounds with potential pharmacological relevance for prostate cancer, particularly through their interaction with SRC and EGFR pathways, warranting further experimental validation.
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- Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Piñeros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2024). Global Cancer Observatory: Cancer Today, International Agency for Research on Cancer. Lyon, France.
- Watson, P. A., Arora, V. K., and Sawyers, C. L. (2015). Emerging Mechanisms of Resistance to Androgen Receptor Inhibitors in Prostate Cancer, Nature Reviews Cancer. doi:10.1038/nrc4016.
- Sfanos, K. S., and de Marzo, A. M. (2012). Prostate Cancer and Inflammation: The Evidence, Histopathology. doi:10.1111/j.1365-2559.2011.04033.x.
- Varaprasad, G. L., Gupta, V. K., Prasad, K., Kim, E., Tej, M. B., Mohanty, P., Verma, H. K., Raju, G. S. R., Bhaskar, L., and Huh, Y. S. (2023). Recent Advances and Future Perspectives in the Therapeutics of Prostate Cancer, Experimental Hematology & Oncology, Vol. 12, No. 1, 80. doi:10.1186/s40164-023-00444-9.
- Gnanapragasam, V. J., Mason, M. D., Shaw, G. L., and Neal, D. E. (2012). The Role of Surgery in High-Risk Localised Prostate Cancer, BJU International, Vol. 109, No. 5, 648–658. doi:10.1111/j.1464-410X.2011.10596.x.
- Termini, D., Den Hartogh, D. J., Jaglanian, A., and Tsiani, E. (2020). Curcumin against Prostate Cancer: Current Evidence, Biomolecules, Vol. 10, No. 11, 1536. doi:10.3390/biom10111536.
- Noviandy, T. R., Idroes, G. M., and Hardi, I. (2024). Machine Learning Approach to Predict AXL Kinase Inhibitor Activity for Cancer Drug Discovery Using XGBoost and Bayesian Optimization, Journal of Soft Computing and Data Mining, Vol. 5, No. 1, 46–56.
- Tan, L., Nuffer, H., Feng, J., Kwan, S. H., Chen, H., Tong, X., and Kong, L. (2020). Antioxidant Properties and Sensory Evaluation of Microgreens from Commercial and Local Farms, Food Science and Human Wellness, Vol. 9, No. 1, 45–51. doi:10.1016/j.fshw.2019.12.002.
- Tallei, T. E., Kepel, B. J., Wungouw, H. I. S., Nurkolis, F., Adam, A. A., and Fatimawali. (2024). A Comprehensive Review on the Antioxidant Activities and Health Benefits of Microgreens: Current Insights and Future Perspectives, International Journal of Food Science and Technology. doi:10.1111/ijfs.16805.
- Tallei, T. E., Ineke, H., Wungouw, S., Kepel, B. J., Celik, I., Niode, N. J., and Barasarathi, J. (2025). Appraisal of Antioxidant Potential in Broccoli Microgreens under Different Drying Techniques Utilizing In Vitro and in Silico Methods, Vol. 3, No. 1. doi:10.60084/mp.v3i1.259.
- Dereje, B., Jacquier, J.-C., Elliott-Kingston, C., Harty, M., and Harbourne, N. (2023). Brassicaceae Microgreens: Phytochemical Compositions, Influences of Growing Practices, Postharvest Technology, Health, and Food Applications, ACS Food Science & Technology, Vol. 3, No. 6, 981–998. doi:10.1021/acsfoodscitech.3c00040.
- Clarke, J. D., Dashwood, R. H., and Ho, E. (2008). Multi-Targeted Prevention of Cancer by Sulforaphane, Cancer Letters. doi:10.1016/j.canlet.2008.04.018.
- Asif Ali, M., Khan, N., Kaleem, N., Ahmad, W., Alharethi, S. H., Alharbi, B., Alhassan, H. H., Al-Enazi, M. M., Razis, A. F. A., Modu, B., Calina, D., and Sharifi-Rad, J. (2023). Anticancer Properties of Sulforaphane: Current Insights at the Molecular Level, Frontiers in Oncology. doi:10.3389/fonc.2023.1168321.
- Fuente, B. de la, López-García, G., Máñez, V., Alegría, A., Barberá, R., and Cilla, A. (2020). Antiproliferative Effect of Bioaccessible Fractions of Four Brassicaceae Microgreens on Human Colon Cancer Cells Linked to Their Phytochemical Composition., Antioxidants (Basel, Switzerland), Vol. 9, No. 5. doi:10.3390/antiox9050368.
- Kahn, M. (2014). Can We Safely Target the WNT Pathway?, Nature Reviews Drug Discovery. doi:10.1038/nrd4233.
- Malumbres, M., and Barbacid, M. (2009). Cell Cycle, CDKs and Cancer: A Changing Paradigm, Nature Reviews Cancer. doi:10.1038/nrc2602.
- Noor, F., Tahir ul Qamar, M., Ashfaq, U. A., Albutti, A., Alwashmi, A. S. S., and Aljasir, M. A. (2022). Network Pharmacology Approach for Medicinal Plants: Review and Assessment, Pharmaceuticals, Vol. 15, No. 5, 572. doi:10.3390/ph15050572.
- Hopkins, A. L. (2008). Network Pharmacology: The Next Paradigm in Drug Discovery, Nature Chemical Biology. doi:10.1038/nchembio.118.
- Wawo, A. E., Simbala, H. E. I., Fatimawali, F., and Tallei, T. E. (2024). A Comprehensive Network Pharmacology Study on the Diabetes-Fighting Capabilities of Yacon Leaf Extract, Malacca Pharmaceutics, Vol. 2, No. 2, 41–51. doi:10.60084/mp.v2i2.161.
- Tallei, T. E., Savitri, M., Lee, D., Rampengan, D. C. H., Park, M. N., Syahputra, R. A., Taslim, N. A., Moon, S., Nurkolis, F., and Kim, B. (2024). A comparative analysis on impact of drying methods on metabolite composition in broccoli microgreens, LWT, Vol. 210, 116866. doi:10.1016/j.lwt.2024.116866.
- Noviandy, T. R., Maulana, A., Idroes, G. M., Suhendra, R., Afidh, R. P. F., and Idroes, R. (2024). An Explainable Multi-Model Stacked Classifier Approach for Predicting Hepatitis C Drug Candidates, Sci, Vol. 6, No. 4, 81. doi:10.3390/sci6040081.
- Pendong, C. H. A., Suoth, E. J., Fatimawali, F., and Tallei, T. E. (2024). Network Pharmacology Approach to Understanding the Antidiabetic Effects of Pineapple Peel Hexane Extract, Malacca Pharmaceutics, Vol. 2, No. 1, 24–32. doi:10.60084/mp.v2i1.162.
- Noviandy, T. R., Idroes, G. M., Mohd Fauzi, F., and Idroes, R. (2024). Application of Ensemble Machine Learning Methods for QSAR Classification of Leukotriene A4 Hydrolase Inhibitors in Drug Discovery, Malacca Pharmaceutics, Vol. 2, No. 2, 68–78. doi:10.60084/mp.v2i2.217.
- Raihan, A., Illahi, A. K., Rokhimah, S., Elisa, T. P. P., and Maliza, R. (2023). Identification of Bioactive Solutions of Corn Silk (Zea mays L.) Extract and Biological Activity Test By Bioinformatics, Jurnal Biologi Tropis, Vol. 23, No. 1, 245–250. doi:10.29303/jbt.v23i1.5846.
- Halliwell, J. A., Frith, T. J. R., Laing, O., Price, C. J., Bower, O. J., Stavish, D., Gokhale, P. J., Hewitt, Z., El-Khamisy, S. F., Barbaric, I., and Andrews, P. W. (2020). Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells, Stem Cell Reports, Vol. 14, No. 6. doi:10.1016/j.stemcr.2020.04.004.
- Austin, W. R., Armijo, A. L., Campbell, D. O., Singh, A. S., Hsieh, T., Nathanson, D., Herschman, H. R., Phelps, M. E., Witte, O. N., Czernin, J., and Radu, C. G. (2012). Nucleoside Salvage Pathway Kinases Regulate Hematopoiesis by Linking Nucleotide Metabolism with Replication Stress, Journal of Experimental Medicine, Vol. 209, No. 12. doi:10.1084/jem.20121061.
- Jiang, T. Y., Cui, X. W., Zeng, T. M., Pan, Y. F., Lin, Y. K., Feng, X. F., Tan, Y. X., Yuan, Z. G., Dong, L. W., and Wang, H. Y. (2023). PTEN Deficiency Facilitates Gemcitabine Efficacy in Cancer by Modulating the Phosphorylation of PP2Ac and DCK, Science Translational Medicine, Vol. 15, No. 704. doi:10.1126/scitranslmed.add7464.
- Wei, Y., Yang, P., Cao, S., and Zhao, L. (2018). The Combination of Curcumin and 5-Fluorouracil in Cancer Therapy, Archives of Pharmacal Research. doi:10.1007/s12272-017-0979-x.
- Proietti, S., Cucina, A., Catizone, A., Ricci, G., Pensotti, A., and Bizzarri, M. (2021). Zebrafish Embryo Extracts Enhance 5-FU Anti-cancer Effects upon Breast Cancer Cells, European Review for Medical and Pharmacological Sciences, Vol. 25, No. 8. doi:10.26355/eurrev_202104_25732.
- Sharma, N., Biswas, S., Al-Dayan, N., Alhegaili, A. S., and Sarwat, M. (2021). Antioxidant Role of Kaempferol in Prevention of Hepatocellular Carcinoma, Antioxidants. doi:10.3390/antiox10091419.
- Zhang, Z., Guo, Y., Chen, M., Chen, F., Liu, B., and Shen, C. (2021). Kaempferol Potentiates the Sensitivity of Pancreatic Cancer Cells to Erlotinib via Inhibition of the PI3K/AKT Signaling Pathway and Epidermal Growth Factor Receptor, Inflammopharmacology, Vol. 29, No. 5. doi:10.1007/s10787-021-00848-1.
- Jeon, S. J., Jung, G. H., Choi, E. Y., Han, E. J., Lee, J. H., Han, S. H., Woo, J. S., Jung, S. H., and Jung, J. Y. (2024). Kaempferol Induces Apoptosis through the MAPK Pathway and Regulates JNK-Mediated Autophagy in MC-3 Cells, Toxicological Research, Vol. 40, No. 1. doi:10.1007/s43188-023-00206-z.
- Ahmad, I., Hoque, M., Alam, S. S. M., Zughaibi, T. A., and Tabrez, S. (2023). Curcumin and Plumbagin Synergistically Target the PI3K/Akt/mTOR Pathway: A Prospective Role in Cancer Treatment, International Journal of Molecular Sciences, Vol. 24, No. 7. doi:10.3390/ijms24076651.
- Apweiler, M., Saliba, S. W., Streyczek, J., Hurrle, T., Gräßle, S., Bräse, S., and Fiebich, B. L. (2021). Targeting Oxidative Stress: Novel Coumarin-Based Inverse Agonists of GPR55, International Journal of Molecular Sciences, Vol. 22, No. 21. doi:10.3390/ijms222111665.
- Pommier, Y., Leo, E., Zhang, H., and Marchand, C. (2010). DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs, Chemistry and Biology. doi:10.1016/j.chembiol.2010.04.012.
- Delgado, J. L., Hsieh, C. M., Chan, N. L., and Hiasa, H. (2018). Topoisomerases As Anticancer Targets, Biochemical Journal. doi:10.1042/BCJ20160583.
- Misheva, M., Johnson, J., and McCullagh, J. (2022). Role of Oxylipins in the Inflammatory-Related Diseases NAFLD, Obesity, and Type 2 Diabetes, Metabolites. doi:10.3390/metabo12121238.
- Menendez, J. A., and Lupu, R. (2007). Fatty Acid Synthase and the Lipogenic Phenotype in Cancer Pathogenesis, Nature Reviews Cancer. doi:10.1038/nrc2222.
- Mukund, V. (2020). Genistein: Its Role in Breast Cancer Growth and Metastasis, Current Drug Metabolism, Vol. 21, No. 1. doi:10.2174/1389200221666200120121919.
- Pavese, J. M., Krishna, S. N., and Bergan, R. C. (2014). Genistein Inhibits Human Prostate Cancer Cell Detachment, Invasion, and Metastasis, American Journal of Clinical Nutrition (Vol. 100). doi:10.3945/ajcn.113.071290.
- Chen, D., Liu, J.-R., Cheng, Y., Cheng, H., He, P., and Sun, Y. (2019). Metabolism of Rhaponticin and Activities of its Metabolite, Rhapontigenin: A Review, Current Medicinal Chemistry, Vol. 27, No. 19. doi:10.2174/0929867326666190121143252.
- Ren, B., Kwah, M. X. Y., Liu, C., Ma, Z., Shanmugam, M. K., Ding, L., Xiang, X., Ho, P. C. L., Wang, L., Ong, P. S., and Goh, B. C. (2021). Resveratrol for Cancer Therapy: Challenges and Future Perspectives, Cancer Letters, Vol. 515. doi:10.1016/j.canlet.2021.05.001.
- Karkon-Shayan, S., Aliashrafzadeh, H., Dianat-Moghadam, H., Rastegar-Pouyani, N., Majidi, M., Zarei, M., Moradi-vastegani, S., Bahramvand, Y., Babaniamansour, S., and Jafarzadeh, E. (2023). Resveratrol as an Antitumor Agent for Glioblastoma Multiforme: Targeting Resistance and Promoting Apoptotic Cell Deaths, Acta Histochemica. doi:10.1016/j.acthis.2023.152058.
- Fatimawali, Tallei, T. E., Kepel, B. J., Bodhi, W., Manampiring, A. E., and Nainu, F. (2023). Molecular Insight into the Pharmacological Potential of Clerodendrum minahassae Leaf Extract for Type-2 Diabetes Management Using the Network Pharmacology Approach, Medicina, Vol. 59, No. 11, 1899. doi:10.3390/medicina59111899.
- Shorning, B. Y., Dass, M. S., Smalley, M. J., and Pearson, H. B. (2020). The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling, International Journal of Molecular Sciences. doi:10.3390/ijms21124507.
- Li, X., Tsauo, J., Geng, C., Zhao, H., Lei, X., and Li, X. (2018). Ginsenoside Rg3 Decreases NHE1 Expression via Inhibiting EGF-EGFR-ERK1/2-HIF-1 α Pathway in Hepatocellular Carcinoma: A Novel Antitumor Mechanism, American Journal of Chinese Medicine, Vol. 46, No. 8. doi:10.1142/S0192415X18500969.
- Katsi, V., Papakonstantinou, I., and Tsioufis, K. (2023). Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management, International Journal of Molecular Sciences. doi:10.3390/ijms241411786.
- Fizazi, K. (2007). The Role of Src in Prostate Cancer, Annals of Oncology. doi:10.1093/annonc/mdm086.
- Raji, L., Tetteh, A., and Amin, A. R. M. R. (2024). Role of c-Src in Carcinogenesis and Drug Resistance, Cancers. doi:10.3390/cancers16010032.
- Ge, S., Jung, D., and Yao, R. (n.d.). ShinyGO: Gene Ontology Enrichment Analysis and Visualization Tool (Version 0.81), from https://bioinformatics.sdstate.edu/go/.
- Kenchappa, R. S., Dovas, A., Argenziano, M. G., Meyer, C. T., Stopfer, L. E., Banu, M. A., Pereira, B., Griffith, J., Mohammad, A., Talele, S., Haddock, A., Zarco, N., Elmquist, W., White, F., Quaranta, V., Sims, P., Canoll, P., and Rosenfeld, S. S. (2022). Activation of STAT3 through Combined SRC and EGFR Signaling Drives Resistance to a Mitotic Kinesin Inhibitor in Glioblastoma, Cell Reports, Vol. 39, No. 12. doi:10.1016/j.celrep.2022.110991.
- Chen, Z., Oh, D., Dubey, A. K., Yao, M., Yang, B., Groves, J. T., and Sheetz, M. (2018). EGFR Family and Src Family Kinase Interactions: Mechanics Matters?, Current Opinion in Cell Biology. doi:10.1016/j.ceb.2017.12.003.
- Chen, A. Y., and Chen, Y. C. (2013). A Review of the Dietary Flavonoid, Kaempferol on Human Health and Cancer Chemoprevention, Food Chemistry. doi:10.1016/j.foodchem.2012.11.139.
- Kim, S. H., and Choi, K. C. (2013). Anti-cancer Effect and Underlying Mechanism(s) of Kaempferol, a Phytoestrogen, on the Regulation of Apoptosis in Diverse Cancer Cell Models, Toxicological Research. doi:10.5487/TR.2013.29.4.229.
- Bach, D. H., Kim, D., and Lee, S. K. (2020). Cancer Chemopreventive Potential of Epidermal Growth Factor Receptor Inhibitors from Natural Products, Natural Products for Cancer Chemoprevention: Single Compounds and Combinations. doi:10.1007/978-3-030-39855-2_14.
- Belli, S., Esposito, D., Servetto, A., Pesapane, A., Formisano, L., and Bianco, R. (2020). C-Src and EGFR Inhibition in Molecular Cancer Therapy: What Else Can We Improve?, Cancers. doi:10.3390/cancers12061489.
- Dash, J. R., Kar, B., and Pattnaik, G. (2024). In-Silico, In-Vitro and In-Vivo Biological Activities of Flavonoids for the Management of Type 2 Diabetes, Current Drug Discovery Technologies, Vol. 21, No. 5. doi:10.2174/0115701638290819231228081120.
- Handschin, C., Podvinec, M., and Meyer, U. A. (2003). In Silico Approaches, and In Vitro and In Vivo Experiments to Predict Induction of Drug Metabolism, Drug News and Perspectives. doi:10.1358/dnp.2003.16.7.829354.
- Stohs, S. J. (2017). Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine, Phytotherapy Research. doi:10.1002/ptr.5879.
- Bui, N. Q., and Kummar, S. (2018). Evolution of Early Phase Clinical Trials in Oncology, Journal of Molecular Medicine. doi:10.1007/s00109-017-1612-7.
- Rawal, T., Mishra, N., Jha, A., Bhatt, A., Tyagi, R. K., Panchal, S., and Butani, S. (2018). Chitosan Nanoparticles of Gamma-Oryzanol: Formulation, Optimization, and In vivo Evaluation of Anti-hyperlipidemic Activity, AAPS PharmSciTech, Vol. 19, No. 4. doi:10.1208/s12249-018-1001-8.
- Waghule, T., Dabholkar, N., Gorantla, S., Rapalli, V. K., Saha, R. N., and Singhvi, G. (2021). Quality by Design (QbD) in the Formulation and Optimization of Liquid Crystalline Nanoparticles (LCNPs): A Risk Based Industrial Approach, Biomedicine and Pharmacotherapy. doi:10.1016/j.biopha.2021.111940.
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Copyright (c) 2025 Puspita Wijaya, Trina Ekawati Tallei, Lydia Estelina Naomi Tendean, Fatimawali Fatimawali, Grace Lendawati Amelia Turalaki, Diana Shintawati Purwanto

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