Analisis Network Pharmacology Senyawa Metabolit Sekunder Tumbuhan Benalu Kopi (Loranthus ferrugineus Roxb.ex Jack Danser) pada Penyakit Kanker Payudara

Authors

Nur Aira Juwita Universitas Sumatera Utara
Wawan Sujarwo Badan Riset dan Inovasi Nasional (BRIN)
Dinda Rizka Manurung Universitas Sumatera Utara

DOI:

Abstract

This study aims to evaluate the potential of coffee bean metabolite compounds as breast anticancer agents through a network pharmacology approach. The method used starts from literature study and PubChem database. Selection of compound eligibility was carried out with SwissADME using Lipinski's Rule of Five criteria. Protein target prediction was done through SwissTargetPrediction, while breast cancer target data was obtained from GeneCards and OMIM. Protein-protein interactions were analyzed with STRING and visualized using Cytoscape. Compound-protein interactions were analyzed through STITCH. The results showed that nine metabolite compounds from coffee bean met the pharmacokinetic criteria, with five main compounds showing anticancer potential is quercetin, oleic acid, linoleic acid, GCG, and PPARA. Protein interaction network analysis identified five central target proteins: IL6, TNF, AKT1, PTGS2, and ESR1. The compound-protein interactions suggest multitarget potential in the modulation of breast cancer-related molecular pathways.

Keywords: Breast Cancer, Loranthus ferrugineus, Network Pharmacology

References

Ali, R. M., & Ismail, N. H. (2015). Ethnopharmacology, phytochemistry, and pharmacology of Loranthus ferrugineus: A review. Journal of Medicinal Plants Research, 9(6), 187–193.

Alshammari, G. M., & Ahmad, M. (2021). Oleic acid exerts cytotoxic effects on breast cancer cells through apoptosis induction and cell cycle arrest. Scientific Reports, 11. https://doi.org/10.1038/s41598-021-92445-z

Arif, R., Bukhari, S. A., Mustafa, G., Ahmed, S., & Albeshr, M. F. (2024). Network pharmacology and experimental validation to explore the potential mechanism of Nigella sativa for the treatment of breast cancer. Pharmaceuticals, 17(5), 617. https://doi.org/10.3390/ph17050617

Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., & Supuran, C. T. (2021). Natural products in drug discovery: Advances and opportunities. Nature Reviews Drug Discovery, 20(3). https://doi.org/10.1038/s41573-020-00114-z

Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016). Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease. Nature Reviews Clinical Oncology, 13(11), 674–690. https://doi.org/10.1038/nrclinonc.2016.66

Bisht, A., Tewari, D., Kumar, S., & Chandra, S. (2024). Network pharmacology, molecular docking, and molecular dynamics simulation to elucidate the mechanism of anti-aging action of Tinospora cordifolia. Molecular Diversity, 28(3), 1743–1763. https://doi.org/10.1007/s11030-023-10684-w

Cancer, B. (2024). Trends in breast cancer incidence and mortality in Indonesia. BMC Cancer. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14332-4. (Diakses pada 27 Agustus 2025).

Chowdhury, A., Gawali, N. B., & Deshmukh, R. (2021). PPARs in breast cancer: Roles, mechanisms and regulation. Chemico-Biological Interactions, 340. https://doi.org/10.1016/j.cbi.2021.109451

Daina, A., Michielin, O., & Zoete, V. (2019). SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Research, 47(W1), W357–W366. https://doi.org/10.1093/nar/gkz382

Dillasamola, D., Dharma, S., & Al Khaira, N. Q. (2015). Perbandingan pengaruh pemberian ekstrak etanol defatting dan ekstrak etanol daun benalu kopi Scurrula ferruginea (Jack) Danser terhadap kadar glukosa darah mencit putih jantan. Scientia: Jurnal Farmasi dan Kesehatan, 5(2), 108. https://doi.org/10.36434/scientia.v5i2.31

Feng, Y., Spezia, M., Huang, S., Yuan, C., Zeng, Z., Zhang, L., dkk. (2018). Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes and Diseases, 5(2), 77–106. https://doi.org/10.1016/j.gendis.2018.05.001

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell. https://doi.org/10.1016/j.cell.2011.02.013

Hassanin, S. O., Hegab, A. M. M., Mekky, R. H., Said, M. A., Khalil, M. G., Hamza, A. A., & Amin, A. (2024). Combining in vitro, in vivo, and network pharmacology assays to identify targets and molecular mechanisms of Spirulina-derived biomolecules against breast cancer. Marine Drugs, 22(7), 328. https://doi.org/10.3390/md22070328

Huang, X. F., Cheng, W. B., Jiang, Y., Liu, Q., Liu, X. H., Xu, W. F., & Huang, H. T. (2020). A network pharmacology based strategy for predicting anti inflammatory targets of Ephedra in treating asthma. International Immunopharmacology, 83, 106423. https://doi.org/10.1016/j.intimp.2020.106423

Jahan, S., Al-saigul, A. M., & Abdelgadir, M. H. (2024). Breast cancer. Journal of the Royal Society of Medicine, 70(8), 515–517.

Jamal, J., Musnina, W. O. S. M., Setiawan, M. R. S., & Rumi, A. (2025). Uji network pharmacology dan docking molekuler senyawa metabolit sekunder Begonia willemii endemik Sulawesi Tengah terhadap reseptor kanker serviks. Borneo Journal of Pharmascientech, 9(1), 144–162. https://doi.org/10.59053/bjp.v9i1.645

Kersten, S. (2014). Integrated physiology and systems biology of PPARα. Molecular Metabolism, 3(4), 354–371. https://doi.org/10.1016/j.molmet.2014.02.002

Kinnel, R., Sharma, S., & Patel, K. (2023). Drug resistance mechanisms in breast cancer: From tumor microenvironment to genetic adaptation. Frontiers in Oncology, 13, 1112255. https://doi.org/10.3389/fonc.2023.1112255

Lee, A. Y., Lee, J. Y., & Chun, J. M. (2020). Exploring the mechanism of Gyejibokryeong-hwan against atherosclerosis using network pharmacology and molecular docking. Plants, 9. https://doi.org/10.3390/plants9121750

Lefebvre, P., Chinetti, G., Fruchart, J. C., & Staels, B. (2006). Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. Journal of Clinical Investigation, 116(13), 571–580. https://doi.org/10.1172/JCI27989

Li, Y., Sun, H., & Chen, Z. (2020). Conjugated linoleic acid suppresses breast cancer cell growth via ERK1/2 and Akt signaling. Biomedicine & Pharmacotherapy, 127. https://doi.org/10.1016/j.biopha.2020.110138

Lipinski, C. A. (2004). Lead- and drug-like compounds: The rule-of-five revolution.

Mahfudz, A. H., Nugraheni, M., & Purwantini, E. (2022). Aktivitas antioksidan dan potensi senyawa bioaktif ekstrak benalu kopi (Loranthus ferrugineus). Jurnal Fitofarmaka Indonesia, 9(2), 134–140.

Malik, A., Salmawati, S., & Rahmawati, A. (2020). Keanekaragaman hayati dan potensi tanaman obat Indonesia. Jurnal Hayati Tropika, 7(1), 55–62.

Margolese, R. G., Hortobagyi, G. N., & Buchholz, T. A. (2019). Breast Cancer Biology. https://doi.org/10.5772/intechopen.78163

Naushafira, A., Siregar, D. L. E., & Manurung, N. (2022). Potensi kuersetin dalam terapi kanker payudara: Tinjauan in silico dan mekanisme molekuler. Jurnal Farmasi Klinik dan Komunitas, 9(1), 20–30.

Newman, D. J., & Cragg, G. M. (2020). Natural products as sources of new drugs over the nearly four decades. Journal of Natural Products, 83(3), 770–803.

Noor, R., Qamar, M. T., Ashfaq, U. A., Albutti, A., Alwahmi, A. S. S., & Alhasir, M. A. (2022). Network pharmacology approach for medicinal plants: Review and assessment. Pharmaceuticals, 15(5), 152. https://doi.org/10.3390/pharmaceutics15050572.

Quail, D. F., & Joyce, J. A. (2013). Microenvironmental regulation of tumor progression and metastasis. Nature Medicine, 19(11), 1423–1437. https://doi.org/10.1038/nm.339,4

Rehman, M. U., Khan, A. Q., & Tahir, M. (2021). Quercetin in cancer management. mechanistic approach. Anti-Cancer Agents in Medicinal Chemistry, 21(2), 165–175. https://doi.org/10.2174/1871520620666200519123311

Setiani, L. A., Saputri, F. C., Yanuar, A., & Mun’im, A. (2024). Determining antihypertensive herbal formulas based on molecular mechanisms and protein- compound interactions of selected Indonesian medicinal plants using a network pharmacological approach. Journal of Applied Pharmaceutical Science, 14(3), 252– 262. https://doi.org/10.7324/JAPS.2024.152201

Sun, Y. S., Zhao, Z., Yang, Z. N., Xu, F., Lu, H. J., Zhu, et all. (2017). Risk factors and preventions of breast cancer. International Journal of Biological Sciences, 13(11), 1387–1397. https://doi.org/10.7150/ijbs.21635

Suparna, K., & Sari, L. M. K. K. S. (2022). Kanker Payudara: Diagnostik, Faktor Risiko, Dan Stadium. Ganesha Medicine, 2(1),42–48. https://doi.org/10.23887/gm.v2i1.47032

Szklarczyk, D., Gable, A. L., Lyon, D., Junge, A., Wyder, S., et al. (2019). STRING v11: protein–protein association networks with increased coverage. Nucleic Acids Research, 4(1), 607–613.

Taniguchi, K., & Karin, M. (2018). IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Seminars in Immunology, 39, 3–11.

Tilburt, J. C., & Kaptchuk, T. J. (2008). Herbal medicine research and global health: An ethical analysis. Bulletin of the World Health Organization, 86(8), 594–599. https://doi.org/10.2471/BLT.07.042820

Verma, A., Patel, K., & Kumar, A. (2024). Targeting drug resistance in breast cancer: the potential of miRNA and nanotechnology-driven delivery systems. Nanoscale Advances, 6(24), 6079–6095. https://doi.org/10.1039/d4na00660g

Wang, K., Liu, R., Li, J., Mao, J., Lei, Y., Wu, J., et al. (2020). Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling. Cell Death & Disease, 11. https://doi.org/10.1038/s41419-020-02726-2%0A%0A

WHO. (2023). Global Breast Cancer Initiative. https://www.who.int/initiatives/global- breast-cancer-initiative/

Wu, N., Yuan, T., Yin, Z., Yuan, X., Sun, J., Wu, Z., Zhang, Q., Redshaw, C., Yang, S., & Dai, X. (2022). Network Pharmacology and Molecular Docking Study of the Chinese Miao Medicine Sidaxue in the Treatment of Rheumatoid Arthritis. Drug Design, Development and Therapy, 16, 435–466. https://doi.org/10.2147/DDDT.S330947

Xiong, X., Zheng, L. W., Ding, Y., Chen, Y. F., Cai, Y. W., Wang, et al. (2025). Breast cancer: pathogenesis and treatments. Signal Transduction and Targeted Therapy, 10(1). https://doi.org/10.1038/s41392- 024-02108-4

Xu, W., Wang, Y., Li, Y., Wang, D., & Liu, H. (2021). Gallocatechin gallate induces apoptosis and inhibits migration of breast cancer cells via regulating the PI3K/AKT and MAPK signaling pathways. Ournal of Cellular Biochemistry, 122(10), 1501– 1513. https://doi.org/10.1002/jcb.29836