Targeting Prostate Cancer with Rambutan Peel-Derived Compounds via Network Pharmacology

Authors

  • Wulandari Putri Utami Medical Education Study Program, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia
  • Trina Ekawati Tallei Department of Biology, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, Indonesia
  • Grace Lendawati Amelia Turalaki Department of Biology, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia
  • Lydia Estelina Naomi Tendean Department of Biology, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia
  • Martha Marie Kaseke Department of Anatomy and Histology, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia
  • Diana Shintawati Purwanto Department of Biochemistry, Faculty of Medicine, Sam Ratulangi University, Manado 95115, Indonesia

DOI:

https://doi.org/10.60084/mp.v3i1.262

Keywords:

Signaling pathway, Rambutan , Network pharmacology, Prostate cancer, Tyrosine kinase

Abstract

Prostate cancer is a prevalent malignancy in men, originating in the prostate gland and often driven by genetic alterations and hormonal dysregulation. Rambutan (Nephelium lappaceum L.) peel, a byproduct of fruit consumption, has demonstrated potential anticancer activity. This study employed a network pharmacology-based in silico approach to evaluate the therapeutic potential of rambutan peel extract in prostate cancer treatment. Bioactive compounds were identified through database searches, and their biological activities were predicted using PASS Online. Pharmacokinetic and toxicity profiles were assessed using ADMETLab 3.0 and Protox 3.0 to evaluate safety and drug-like properties. Potential target proteins were identified via SwissTargetPrediction and GeneCards, while protein-protein interaction networks were constructed using STRING. The pharmacological networks were visualized using Cytoscape to elucidate molecular mechanisms of action. The analysis identified 28 bioactive compounds in rambutan peel extract, with 11 demonstrating activity against prostate cancer (Pa > 0.5). These compounds were deemed safe based on Lipinski's Rule of Five (Ro5) and categorized within toxicity classes V and VI. Rambutan peel extract was found to target 501 proteins associated with prostate cancer, including key pathways involved in resistance to EGFR tyrosine kinase inhibitors. Network pharmacology analysis highlighted several key target genes, including SRC, GNAI1, PIK3CA, PIK3CD, MAPK1, MAPK3, AKT1, GNAI3, PRKCA, and HSP90AA1. Among these, SRC exhibited the highest centrality score, underscoring its pivotal role in disrupting tumorigenic and metastatic signaling pathways, suppressing cancer cell proliferation, and enhancing therapeutic responses. These findings suggest that rambutan peel extract holds promise as a natural therapeutic agent for prostate cancer, warranting further experimental and clinical validation.

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References

  1. Rawla, P. (2019). Epidemiology of Prostate Cancer, World Journal of Oncology, Vol. 10, No. 2, 63.
  2. Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., and Jemal, A. (2024). Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA: A Cancer Journal for Clinicians, Vol. 74, No. 3, 229–263.
  3. Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Piñeros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2020). Global Cancer Observatory: Cancer Today, Lyon: International Agency for Research on Cancer, Vol. 20182020.
  4. Christina, S., Sanchia, H., and Angka, R. N. (2022). Kanker Prostat: Risiko Dan Pencegahannya., Jurnal MedScientiae, Vol. 1, No. 2, 73–81.
  5. Pernar, C. H., Ebot, E. M., Wilson, K. M., and Mucci, L. A. (2018). The Epidemiology of Prostate Cancer, Cold Spring Harbor Perspectives in Medicine, Vol. 8, No. 12, a030361.
  6. Safriadi, F., Umbas, R., Hakim, L., Warli, S. M., Hamid, A. R., Hudaya, S., Ismy, J., Soerohardjo, I., Widjanarko, S., and Yudiana, W. (2022). Panduan Penanganan Kanker Prostat, Ikatan Ahli Urologi Indonesia.
  7. Pinho, S., Coelho, J. M. P., Gaspar, M. M., and Reis, C. P. (2024). Advances in Localized Prostate Cancer: A Special Focus on Photothermal Therapy, European Journal of Pharmacology, 176982. doi:10.1016/j.ejphar.2024.176982.
  8. Yang, J., Wang, C., Ma, X., Li, J., Yuan, H., Tan, R., Ling, L., and Zhou, X. (2024). A New Exploration: Characterization of the Differentiation Trajectory of Prostate Cancer Cells, Discover Oncology, Vol. 15, No. 1, 426. doi:10.1007/s12672-024-01303-7.
  9. Ikatan Ahli Urologi Indonesia. (2022). Panduan Penanganan Kanker Prostat.
  10. Mydlo, J. H., and Godec, C. J. (2015). Prostate Cancer: Science and Clinical Practice, Academic Press.
  11. Ferri, F. F. (2024). Ferri’s Clinical Advisor 2025: 5 Books in 1, Elsevier Health Sciences.
  12. Xiao, J., Zhang, M., and Wu, D. (2024). Side Effects of Prostate Cancer Therapies and Potential Management, Journal of Biological Methods, Vol. 11, No. 3, e99010018.
  13. Wang, G., Zhao, D., Spring, D. J., and DePinho, R. A. (2018). Genetics and Biology of Prostate Cancer, Genes & Development, Vol. 32, Nos. 17–18, 1105–1140.
  14. Khan, S., Chang, S.-H., Wang, M., Kim, E. H., Schoen, M. W., Rocuskie-Marker, C., and Drake, B. F. (2023). Local Treatment and Treatment-Related Adverse Effects among Patients with Advanced Prostate Cancer, JAMA Network Open, Vol. 6, No. 12, e2348057–e2348057.
  15. Beltran, H., Hruszkewycz, A., Scher, H. I., Hildesheim, J., Isaacs, J., Yu, E. Y., Kelly, K., Lin, D., Dicker, A., and Arnold, J. (2019). The Role of Lineage Plasticity in Prostate Cancer Therapy Resistance, Clinical Cancer Research, Vol. 25, No. 23, 6916–6924.
  16. Campbell, M. F., Walsh, P. C., Wein, A. J., Partin, A. W., Dmochowski, R. R., Kavoussi, L. R., and Peters, C. C. A. (2021). Campbell-Walsh-Wein Urology, (No Title).
  17. Suhendra, R., Husdayanti, N., Suryadi, S., Juliwardi, I., Sanusi, S., Ridho, A., Ardiansyah, M., Murhaban, M., and Ikhsan, I. (2023). Cardiovascular Disease Prediction Using Gradient Boosting Classifier, Infolitika Journal of Data Science, Vol. 1, No. 2, 56–62. doi:10.60084/ijds.v1i2.131.
  18. Huang, M., Lu, J.-J., and Ding, J. (2021). Natural Products in Cancer Therapy: Past, Present and Future, Natural Products and Bioprospecting, Vol. 11, No. 1, 5–13. doi:10.1007/s13659-020-00293-7.
  19. West, H. (Jack). (2018). Complementary and Alternative Medicine in Cancer Care, JAMA Oncology, Vol. 4, No. 1, 139–139. doi:10.1001/jamaoncol.2017.3120.
  20. Prasetyorini, B. E., Kusumawardani, A., Fitriani, F., Rachman, P. O., Amelinda, N., and Ramadhani, A. (2022). Analisis In Silico Senyawa Aktif Batang Kayu Bajakah (Spatholobus Littoralis Hassk) Sebagai Terapi Psoriasis, Herb-Medicine Journal: Terbitan Berkala Ilmiah Herbal, Kedokteran Dan Kesehatan, Vol. 5, No. 1, 26–35.
  21. Wijaya, P., Tallei, T. E., Tendean, L. E. N., Fatimawali, F., Turalaki, G. L. A., and Purwanto, D. S. (2025). Network Pharmacology Insights into Broccoli Microgreens for Prostate Cancer, Heca Journal of Applied Sciences, Vol. 3, No. 1, 1–16. doi:10.60084/hjas.v3i1.264.
  22. Afzaal, M., Saeed, F., Bibi, M., Ejaz, A., Shah, Y. A., Faisal, Z., Ateeq, H., Akram, N., Asghar, A., and Shah, M. A. (2023). Nutritional, Pharmaceutical, and Functional Aspects of Rambutan in Industrial Perspective: An Updated Review, Food Science & Nutrition, Vol. 11, No. 7, 3675–3685.
  23. Sadino, A. (2017). Aktivitas Farmakologis, Senyawa Aktif Dan Mekanisme Kerja Rambutan (Nephelium lappaceum L.), J of Farmaka, Vol. 15, 16–25.
  24. Marni, L. G. (2023). Review Pemanfaatan Kulit Buah Rambutan (Nephelium lappaceum L.) Sebagai Inhibitor Korosi, JSSIT: Jurnal Sains Dan Sains Terapan, Vol. 1, No. 1.
  25. Kamran, S., Sinniah, A., Abdulghani, M. A., and Alshawsh, M. A. (2022). Therapeutic Potential of Certain Terpenoids as Anticancer Agents: A Scoping Review, Cancers, Vol. 14, No. 5, 1100.
  26. Elekofehinti, O. O., Iwaloye, O., Olawale, F., and Ariyo, E. O. (2021). Saponins in Cancer Treatment: Current Progress and Future Prospects, Pathophysiology, Vol. 28, No. 2, 250–272.
  27. Khonkarn, R., Okonogi, S., Ampasavate, C., and Anuchapreeda, S. (2010). Investigation of Fruit Peel Extracts as Sources for Compounds with Antioxidant and Antiproliferative Activities against Human Cell Lines, Food and Chemical Toxicology, Vol. 48, Nos. 8–9, 2122–2129.
  28. Torgbo, S., Rugthaworn, P., Sukatta, U., and Sukyai, P. (2022). Biological Characterization and Quantification of Rambutan (Nephelium Lappaceum L.) Peel Extract as a Potential Source of Valuable Minerals and Ellagitannins for Industrial Applications, ACS Omega, Vol. 7, No. 38, 34647–34656.
  29. Tingting, Z., Xiuli, Z., Kun, W., Liping, S., and Yongliang, Z. (2022). A Review: Extraction, Phytochemicals, and Biological Activities of Rambutan (Nephelium Lappaceum L) Peel Extract, Heliyon, Vol. 8, No. 11, e11314. doi:10.1016/j.heliyon.2022.e11314.
  30. Khaizil Emylia, Z., Aina, S., and Dasuki, S. M. (2013). Preliminary Study on Anti-Proliferative Activity of Methanolic Extract of Nephelium Lappaceum Peels towards Breast (MDA-MB-231), Cervical (HeLa) and Osteosarcoma (MG-63) Cancer Cell Lines, Health, Vol. 4, No. 2, 66–79.
  31. Jantapaso, H., and Mittraparp-Arthorn, P. (2022). Phytochemical Composition and Bioactivities of Aqueous Extract of Rambutan (Nephelium Lappaceum L. Cv. Rong Rian) Peel, Antioxidants, Vol. 11, No. 5, 956.
  32. Perumal, A., AlSalhi, M. S., Kanakarajan, S., Devanesan, S., Selvaraj, R., and Tamizhazhagan, V. (2021). Phytochemical Evaluation and Anticancer Activity of Rambutan (Nephelium Lappaceum) Fruit Endocarp Extracts against Human Hepatocellular Carcinoma (HepG-2) Cells, Saudi Journal of Biological Sciences, Vol. 28, No. 3, 1816–1825.
  33. Noor, F., Tahir ul Qamar, M., Ashfaq, U. A., Albutti, A., Alwashmi, A. S., and Aljasir, M. A. (2022). Network Pharmacology Approach for Medicinal Plants: Review and Assessment, Pharmaceuticals, Vol. 15, No. 5, 572.
  34. Yuliana, I., and Suhartono, E. (2023). Prediksi Potensi Antidiabetes Melalui Molecular Docking Kandungan Peptide Daun Karamunting (Rhodomyrtus Tomentosa) Melalui Inhibisi Enzim Α-Glucosidase (Vol. 4). Presented at the Lambung Mangkurat Medical Seminar, 157–164.
  35. Fath, D. H. M., Muchlisin, M. A., and Jamil, A. S. (2024). Analisis Network Pharmacology Senyawa Metabolit Sekunder Tanaman Lengkuas (Alpinia Galanga) Pada Penyakit Kanker, Journal of Islamic Pharmacy, Vol. 9, No. 1, 43–49.
  36. 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.
  37. Tallei, T. E., Yelnetty, A., Marfuah, S., Tania, A. D., Kalalo, M. J., Kepel, B. J., Niode, N. J., Kusumawaty, D., and Idroes, R. (2022). Evaluation of the Potential for Immunomodulatory and Anti-Inflammatory Properties of Phytoconstituents Derived from Pineapple [Ananas Comosus (L.) Merr.] Peel Extract Using an In Silico Approach., Philippine Journal of Science, Vol. 151, No. 1.
  38. Zhong, J. (2016). RAS and Downstream RAF-MEK and PI3K-AKT Signaling in Neuronal Development, Function and Dysfunction, Biological Chemistry, Vol. 397, No. 3, 215–222.
  39. Varkaris, A., Katsiampoura, A. D., Araujo, J. C., Gallick, G. E., and Corn, P. G. (2014). Src Signaling Pathways in Prostate Cancer, Cancer and Metastasis Reviews, Vol. 33, 595–606.
  40. Zhou, J., Du, T., Li, B., Rong, Y., Verkhratsky, A., and Peng, L. (2015). Crosstalk between MAPK/ERK and PI3K/AKT Signal Pathways during Brain Ischemia/Reperfusion, ASN Neuro, Vol. 7, No. 5, 1759091415602463.
  41. Xiao, X., Wang, W., Li, Y., Yang, D., Li, X., Shen, C., Liu, Y., Ke, X., Guo, S., and Guo, Z. (2018). HSP90AA1-Mediated Autophagy Promotes Drug Resistance in Osteosarcoma, Journal of Experimental & Clinical Cancer Research, Vol. 37, 1–13.
  42. Varkaris, A., Katsiampoura, A. D., Araujo, J. C., Gallick, G. E., and Corn, P. G. (2014). Src Signaling Pathways in Prostate Cancer, Cancer and Metastasis Reviews, Vol. 33, 595–606.
  43. Sigismund, S., Avanzato, D., and Lanzetti, L. (2018). Emerging Functions of the EGFR in Cancer, Molecular Oncology, Vol. 12, No. 1, 3–20.
  44. Thomas, R., and Weihua, Z. (2019). Rethink of EGFR in Cancer with Its Kinase Independent Function on Board, Frontiers in Oncology, Vol. 9, 800.
  45. Kopetz, S. (2007). Targeting SRC and Epidermal Growth Factor Receptor in Colorectal Cancer: Rationale and Progress into the Clinic, Gastrointestinal Cancer Research: GCR, Vol. 1, No. 4 Suppl 2, S37.

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Published

2025-03-27

How to Cite

Utami, W. P. ., Tallei, T. E., Turalaki, G. L. A., Tendean, L. E. N., Kaseke, M. M., & Purwanto, D. S. (2025). Targeting Prostate Cancer with Rambutan Peel-Derived Compounds via Network Pharmacology. Malacca Pharmaceutics, 3(1), 42–49. https://doi.org/10.60084/mp.v3i1.262

Issue

Vol. 3 No. 1 (2025): March 2025

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Article

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Copyright (c) 2025 Wulandari Putri Utami, Trina Ekawati Tallei, Grace Lendawati Amelia Turalaki, Lydia Estelina Naomi Tendean, Martha Marie Kaseke, Diana Shintawati Purwanto

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