Main Article Content

Abstract

Breast cancer is a leading cause of cancer-related deaths in Indonesia. However, the drugs that are commonly used for treatment can cause side effects and become resistant over time. A study was conducted to test the cytotoxic activity of broadleaf mahogany (Swietenia macrophylla) seed extract on MCF-7 breast cancer cells in vitro. The study aimed to predict active compounds in the broadleaf mahogany seeds that have the potential to act as anti-breast cancer agents using in silico analysis. Molecular docking, visualization of the interaction between the receptor and the ligands, and physicochemical analysis were used to determine the most promising compounds. The receptors used were fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), insulin-like growth factor type 1 receptor (IGF-1R), estrogen receptor (ER-α), and progesterone receptor (PR). The results showed that 12 compounds have the potential to be active as anti-breast cancer agents. Three of these compounds, 3β,6-dihydroxydihydrocarapine, stigmasterol, and 7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-chroman-4-one, were predicted to have similar mechanisms of inhibition as a comparator drug based on binding site similarity values. These compounds are predicted to be taken orally and are promising for further research.

Keywords

MCF-7 stigmasterol molecular docking limonoid oral drug

Article Details

Author Biographies

Hanifah Dwi Cahya, Department of Chemistry, Faculty of Mathematics and Natural Science, IPB University, Bogor, Indonesia

Department of Chemistry, Faculty of Mathematics and Natural Science, IPB University, Bogor, Indonesia

Shadila Fira Asoka, Department of Chemistry, Faculty of Mathematics and Natural Science, IPB University, Bogor, Indonesia

Department of Chemistry, Faculty of Mathematics and Natural Science, IPB University, Bogor, Indonesia

Kosei Yamauchi, United Graduate School of Agriculture Sciences, Gifu University, Gifu, Japan

United Graduate School of Agriculture Sciences, Gifu University, Japan

How to Cite
Cahya, H. D., Nurlela, N., Tohir, D., Batubara, I., Asoka, S. F. ., & Yamauchi, K. (2024). Potential of Active Compounds in Broadleaf Mahogany (Swietenia macrophylla) Seeds Against Breast Cancer Cells Based on In Silico Study. Jurnal Jamu Indonesia, 9(1), 41–51. https://doi.org/10.29244/jji.v9i1.296

References

  1. Acharya, R., Chacko, S., Bose, P., Lapenna, A., & Pattanayak, S. P. (2019). Structure based multitargeted molecular docking analysis of selected furnaocoumarins agains breast cancer. Scientific Reports, 9(15743), 1–13.
  2. Asoka, S. F., Wahyuni, W. T., Batubara, I., & Wahyudi, S. T. (2022a). Red ginger (Zingiber officinale var. rubrum): Its essential oil content and potential as an anti-propionibacterium acnes by molecular docking. AIP Conference Proceedings, 2563(1), 1–9. https://doi.org/10.1063/5.0103211.
  3. Asoka, S. F., Batubara, I., Lestari, A. R., Wahyuni, W. T., & Wahyudi, S. T. (2022b). Compounds in Indonesian ginger rhizome extracts and their potential for anti-skin aging based on molecular docking. Cosmetics, 9(128), 1–15.
  4. Bronowska, A. K. (2011). Thermodynamics of ligand-protein interactions: Implications for molecular design. Thermodynamics–Interaction Studies–Solids, Liquids and Gases, 1–49. https://doi.org/10.5772/19447.
  5. Chen, X. H., & Sharon, E. (2013). IGF-1R as an anti-cancer target—trials and tribulations. Chinese Journal of Cancer, 32(5), 242–252. https://doi.org/10.5732/cjc.012.10263.
  6. Choucair, A. (2018). Crosstalk between IGF-1 and estrogen receptor non-genomic signaling pathway in breast cancer. Cancer. Lyon: Université de Lyon.
  7. Comşa, Ş., Cîmpean, A. M., & Raica, M. (2015). The story of MCF-7 breast cancer cell line: 40 years of experience in research. Anticancer Research, 35(6), 3147–3154.
  8. Dawood, D. H., Nossier, E. S., Ali, M. M., & Mahmoud, A. E. (2020). Synthesis and molecular docking study of new pyrazole derivatives as potent anti-breast cancer agents targeting VEGFR-2 kinase. Bioorganic Chemistry, 1(1), 1–40.
  9. Eberhardt, J., Santos-Martins, D., Tillack, A. F., & Forli, S. (2021). AutoDock Vina 1.2.0: New docking methods, expanded force field, and phyton binding. Journal of Chemical Information and Modeling, 61(8), 3891–898. https://doi.org/10.1021/acs.jcim.1c00203.
  10. Erber, R., Rübner, M., Davenport, S., Hauke, S., Beckmann, M. W., Hartmann, A., Häberle L, Gass, P., Press, M. F., & Fasching, P. A. (2020). Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients. Breast Cancer Research and Treatment, 184(2), 311–324. https://doi.org/10.1007/s10549-020-05865-2.
  11. Jiao, Q., Bi, L., Ren, Y., Song, S., Wang, Q., & Wang, Y. (2018). Advances in studies of tyrosine kinase inhibitors and their acquired resistance. Molecular Cancer, 17(1),1–12. https://doi.org/10.1186/s12943-018-0801-5.
  12. Kallander, L. S., Washburn, D. G., Hoang, T. H., Frazee, J. S., Stoy, P., & Johnson, L., et al. (2010). Improving the developability profile of pyrrolidine progesterone receptor partial agonists. Bioorganic & Medicinal Chemistry Letters, 20(2010), 371–374. https://doi.org/10.1016/j.bmcl.2009.10.092.
  13. Kintamani, E., Batubara, I., Kusmana, C., Tiryana, T., Mirmanto, E., & Asoka S. F. (2023). Essential oil compounds of andaliman (Zanthoxylum acanthopodium DC.) fruit varieties and their utilization as skin anti-aging using molecular docking. Life, 13(754), 1–13.
  14. Lestari, A. R., Batubara, I., Wahyudi, S. T., Ilmiawati, A., & Achmadi, S. S. (2022). Bioactive compounds in garlic (Allium sativum) and black garlic as antigout agents, using computer simulation. Life, 12(1131), 1–15.
  15. Lian, L., Li, X. L., Xu, M. D., Li, X. M., Wu, M. Y., Zang, Y., Tao, M., Li, W., Shen, X. M., & Zhou, C., et al. (2019). VEGFR2 promotes tumorigenesis and metastasis in a pro- angiogenic-independent way in gastric cancer. BioMed Central Cancer, 19(183), 1–15. https://doi.org/10.1186/s12885-019-5322-0.
  16. Lins, L., & Brasseur, R. (1995). The hydrophobic effect in protein folding. The Federation of American Societies for Experimental Biology Journal, 9, 535–540. https://doi.org/10.1096/fasebj.9.7.7737462.
  17. Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 64, 4– 17. https://doi.org/10.1016/j.addr.2012.09.019.
  18. Lopez-Camacho, E., Garcia-Godoy, M. J., Garcia-Nieto, J., Nebro, A. J., & Aladana-Montes, J. F. (2019). Optimizing ligand conformations in flexible protein targets: a multi- objective strategy. Soft Computing, 24, 10705–10719. https://doi.org/10.1007/s00500- 019-04575-2.
  19. Mathew, A. J., & Raj N. N. (2009). In silico docking studies on anticancer drugs for breast cancer. In: International Association of Computer Science and Information Technology-Spring Conference, 2009 Apr 17–20, Singapore. Los Alamitos: IEEE Computer Society, 567–570. [Accessed 2021 Jan 1]. https://www.researchgate.net/publication/224565236InsilicoDockingStudiesonAnticancer_Drugs_for_Breast_Cancer
  20. Meng, X., Zhang, H., Mezei, M., & Cui, M. (2011). Molecular docking: A powerful approach for structure-based drug discovery. Current Computer Aided Drug Design, 7(2), 146–157.
  21. Murray, R. K., Bender, D. A., Botham, K. M., Kennely, P. J., Rodwell, V. W., & Weil, P. A. (2012). Biochemistry Harper Edition 29. Jakarta (ID): EGC.
  22. Nelson, D. L., & Cox, M. M. (2012). Principles of Biochemistry. New York (US): W.H. Freeman and Company.
  23. Nogara, P. A., Saraiva, R. A., Bueno, D. C., Lissner, L. J., Corte, C. L. D., Braga, M. M., Rosemberg, D. B., & Rocha, J. B. T. (2015). Virtual screening of acetylcholinesterase inhibitors using the Lipinski’s rule of five and ZINC databank. BioMed Research International, 2015, 1–8. https://doi.org/10.1155/2015/870389.
  24. Nurlela, N., Awaluddin, F., Batubara, I., & Wahyudi, S. T. (2022). Computational study of kaurene diterpenoids for antivirals against SARS-CoV-2. Journal of Applied Pharmaceutical Science, 12(8), 112–129.
  25. Prasetiawati, R., Suherman, M., Permana, B., & Rahmawati. (2021). Molecular docking study of anthocyanidin compounds against epidermal growth factor receptor (EGFR) as anti-lung cancer. Indonesian Journal of Pharmaceutical Science and Technology, 8(1), 8–20. https://doi.org/10.24198/ijpst.v8i1.29872.
  26. Prayogo, G. (2021). Aktivitas antikanker payudara senyawa aktif asal batang Spatholobus suberectus secara in silico [skripsi]. Bogor: Institut Pertanian Bogor.
  27. Pinto, L. C., Mesquita, F. P., Barreto, L. H., Souza, P. F., Ramos, I. N., Pinto, A. V., Soares, B. M., da Silva, M. N., Burbano, R. M., & Montenegro, R. C. (2021). Anticancer potential of limonoids from Swietenia macrophylla: genotoxic, antiproliferative and proapoptotic effects towards human colorectal cancer. Life Sciences, 285(119949).
  28. Sharp, K. A., & Honig, B. (1990). Electrostatic interactions in macromolecules: theory and applications. Annual Review of Biophysics and Biophysical Chemistry, 19, 301–322.
  29. Sumathy, A., Palanisamy, S., Arathi, K., Aswthi, U., & Hamna, F. K. (2016). Docking analysis of potent inhibitors of topomeirase IV as potensial antimicrobal agents. Asian Journal of Pharmaceutical and Health Sciences, 1467–1471.
  30. Sun, Y., Sun, X., & Shen, B. (2017). Molecular Imaging of IGF-1R in Cancer. Molecular Imaging, 16, 1–7.
  31. Syahputra, G., Ambarsari, L., & Sumaryada, T. (2014). Simulation of docking of curcumin enol bisdemethoxycurcumin and its analogues as 12-lipoxygenase enzyme inhibitors. Jurnal Biofisika, 10(1), 55–67.
  32. Telrandhe, U. B., Kosalge, S. B., Parihar, S., Sharma, D., & Lade, S. N. (2022). Phytochemistry and Pharmacological Activities of Swietenia macrophylla King (Meliaceae). Scholars Academic Journal of Pharmacy, 11(1), 6-12. https://doi.org/10.36347/sajp.2022.v11i01.002
  33. Tohir, D., Sari, F., & Suparto, I. H. (2020). Cytotoxicity of the most active fraction of the seeds of Swietenia macrophylla using human breast cancer MCF-7 cells. Jurnal Kimia Sains dan Aplikasi, 23(7), 234–237. https://doi.org/10.14710/jksa.23.7.234-237.
  34. Trabert, B., Sherman, M. E., Kannan, N., & Stanczyk, F. Z. (2020). Progesterone and breast cancer. Endocrine Reviews, 41(2), 320–344.
  35. Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient, optimization and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334.
  36. Vegeto, E., Wagner, B. L., Imhof, M. O., & McDonnell, D. P. (1996). The molecular pharmacology of ovarian steroid receptors. Vitamins and Hormones, 52(C), 99–128. https://doi.org/10.1016/S0083-6729(08)60408-2.
  37. Wang, G., Sun, Y., Jin, W., Yu, Y., Zhu, J., & Liu, J. (2022). Limonoids from Swietenia macrophylla and their antitumor activities in A375 human malignant melanoma cells. Biorganic Chemistry, 123(1), 54–61.
  38. Widyasari, E. M., Sriyani, M. E., Daruwati, I., Halimah, I., & Nuraeni, W. (2019). Physico-chemical characteristics of compounds marked 99mTc-Kuersetin. Jurnal Sains dan Teknologi Nuklir Indonesia, 20(1), 9–18. https://doi.org/10.17146/jstni.2019.1.1.4108.
  39. Yasman, S., Yanuar, A., Tamimi, Z., & Rezi, R. S. (2020). In silico analysis of sea cucumber bioactive compounds as anti-breast cancer mechanism using AutoDock Vina. Iranian Journal of Pharmaceutical Sciences, 16(1), 1–8. https://doi.org/10.22034/IJPS.2019.91745.1467.
  40. Zattarin, E., Leporati, R., Ligordo, F., Lobefaro, R., Vinginia, A., Pruneri, G., & Verneri, C. 2020. Review: Hormone receptor loss in breast cancer: molecular mechanisms, clinical settings, and therapeutic implications. Cells, 9(2644), 1–23. https://doi.org/10.3390/cells9122644.
  41. Zhao, M., & Ramaswamy, B. (2014). Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer. World Journal of Clinical Oncology, 5(3), 248–262. https://doi.org/10.5306/wjco.v5.i3.248.