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DOI :10.26650/ijegeo.1573082   IUP :10.26650/ijegeo.1573082    Tam Metin (PDF)

Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches

Onur Ertik

Breast cancer rates are on the rise, particularly among women. Ongoing research is focused on finding effective treatments for this form of cancer. For centuries, plants have been harnessed for their therapeutic properties, with their chemical compounds shedding light on drug development for a wide range of ailments. This investigation aims to explore the potential of certain bioactive 17 compounds present in Momordica charantia (MC) fruit, known to inhibit the growth of breast cancer tumours. Specifically, the study delves into their interactions with critical enzymes—epidermal growth factor receptor (EFGR) and nudix-linked to moiety X-5 (NUDT5)—that are implicated in breast cancer development, utilizing in silico methods. For this purpose, firstly, iGemdock, DockThor and SwissDock were used for the first evaluation and it was observed that the binding affinities of bioactive compounds. In all three docking, compound 16 (Momordicoside L) has shown better results than standard molecules in EGFR and NUDT5. Therefore, docking was applied for compound 16 in HER2 and HER3, revealing a notably high binding affinity, especially for HER2. The results indicate that compound 16 is a potent inhibitor candidate for EGFR, HER2, HER3, and NUDT5, paving the way for further studies. 


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Referanslar

  • Aertgeerts, K., Skene, R., Yano, J., Sang, B. C., Zou, H., Snell, G., Jenning, A., Iwamoto, K., Habuka, N., Hirokawa, A., Ishikawa, T., Tanaka, T., Miki, H., Ohta, Y., Sogabe, S. (2011). Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. Journal of Biological Chemistry, 286(21), 18756-18765. google scholar
  • Dai, Y., Wang, W., Sun, Q., Tuohayi, J. (2018). Ginsenoside Rg3 promotes the antitumor activity of gefitinib in lung cancer cell lines. Experimental and Therapeutic Medicine, 17(1), 953-959. google scholar
  • 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-W364. google scholar
  • de Magalhâes, C. S., Almeida, D. M., Barbosa, H. J. C., Dardenne, L. E. (2014). A dynamic niching genetic algorithm strategy for docking highly flexible ligands. Information Sciences, 289, 206-224. google scholar
  • Duke, J. A. (1992). Handbook of phytochemical constituents of GRAS herbs and other economic plants. Boca Raton, FL. CRC Press. google scholar
  • Feng, T., Wan, Y., Dai, B., Liu, Y. (2023). Anticancer activity of bitter melon-derived vesicles extract against breast cancer. Cells, 12(6), 824. google scholar
  • Funakoshi, Y., Wang, Y., Semba, T., Masuda, H., Hout, D., Ueno, N. T., Wang, X. (2019). Comparison of molecular profile in triple-negative inflammatory and non-inflammatory breast cancer not of mesenchymal stem-like subtype. PLOS ONE, 14(9), e0222336. google scholar
  • Grosdidier, A., Zoete, V., Michielin, O. (2011). SwissDock, a protein-small molecule docking web service based on EADock DSS. Nucleic Acids Research, 39, W270-W277. google scholar
  • Grosdidier, Aurelien, Zoete, V., Michielin, O. (2011). Fast docking using the CHARMM force field with EADock DSS. Journal of Computational Chemistry, 32(10), 2149-2159. google scholar
  • Guedes, I. A., Barreto, A. M. S., Marinho, D., Krempser, E., Kuenemann, M. A., Sperandio, O., Dardenne, L. E., Miteva, M. A. (2021). New machine learning and physics-based scoring functions for drug discovery. Scientific Reports, 11(1), 3198. google scholar
  • Guedes, I. A., Costa, L. S. C., dos Santos, K. B., Karl, A. L. M., Rocha, G. K., Teixeira, I. M., Galheigo, M. M., Medeiros, V., Krempser, E., Custodio, F. L., Barbosa, H. J. C., Nicolas, M. F., Dardenne, L. E. (2021). Drug design and repurposing with DockThor-VS web server focusing on SARS-CoV-2 therapeutic targets and their non-synonym variants. Scientific Reports, 11(1), 5543. google scholar
  • Harbeck, N., Penault-Llorca, F., Cortes, J., Gnant, M., Houssami, N., Poortmans, P., Ruddy, K., Tsang, J., Cardoso, F. (2019). Breast cancer. Nature Reviews Disease Primers, 5(1),66. google scholar
  • Hong, R., Xu, B. (2022). Breast cancer: an up-to-date review and future perspectives. Cancer Communications, 42(10), 913-936. google scholar
  • Hsu, K. C., Chen, Y. F., Lin, S. R., Yang, J. M. (2011). iGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis. BMC Bioinformatics, 12, S33. google scholar
  • Jamroz, M., Kolinski, A., Kmiecik, S. (2014). CABS-flex predictions of protein flexibility compared with NMR ensembles. Bioinformatics, 30(15), 2150-2154. google scholar
  • Jimenez, J., Doerr, S., Martmez-Rosell, G., Rose, A. S., De Fabritiis, G. (2017). DeepSite: protein-binding site predictor using 3D-convolutional neural networks. Bioinformatics, 33(19), 3036-3042. google scholar
  • Jin, Y., Liu, T., Luo, H., Liu, Y., Liu, D. (2022). Targeting epigenetic regulatory enzymes for cancer therapeutics: novel small-molecule epidrug development. Frontiers in Oncology, 12, 848221. google scholar
  • Kilcar, A. Y., Yildiz, O., Dogan, T., Sulu, E., Takan, G., Muftuler, F. Z. B. (2020). The effect of bitter melon (Momordica charantia) extract on the uptake of 99mtc labeled paclitaxel: in vitro monitoring in breast cancer cells. Anti-Cancer Agents in Medicinal Chemistry, 20(12), 1497-1503. google scholar
  • Kim, S., Thiessen, P. A., Bolton, E. E., Chen, J., Fu, G., Gindulyte, A., Han, L., He, J., He, S., Shoemaker, Wang, J., Yu, B., Zhang, J., B. A., Bryant, S. H. (2015). PubChem Substance and Compound databases. Nucleic Acids Research, 44(D1), D1202-D1213. google scholar
  • Kmiecik, S., Gront, D., Kolinski, M., Wieteska, L., Dawid, A. E., Kolinski, A. (2016). Coarse-grained protein models and their applications. Chemical Reviews, 116(14), 7898-7936. google scholar
  • Kurcinski, M., Oleniecki, T., Ciemny, M. P., Kuriata, A., Kolinski, A., Kmiecik, S. (2018). CABS-flex standalone: a simulation environment for fast modeling of protein flexibility. Bioinformatics, 35(4), 694-695. google scholar
  • Lee, J. S., Yoon, I. S., Lee, M. S., Cha, E. Y., Thuong, P. T., Diep, T. T., Kim, J. R. (2013). Anticancer activity of pristimerin in epidermal growth factor receptor 2-positive skbr3 human breast cancer cells. Biological and Pharmaceutical Bulletin, 36(2), 316-325. google scholar
  • Li, S., Gao, Y., Ma, W., Guo, W., Zhou, G., Cheng, T., Liu, Y. (2014). EGFR signaling-dependent inhibition of glioblastoma growth by ginsenoside Rh2. Tumor Biology, 35(6), 5593-5598. google scholar
  • Li, Z., Xia, A., Li, S., Yang, G., Jin, W., Zhang, M., Wang, S. (2020). The pharmacological properties and therapeutic use of bitter melon (Momordica charantia L.). Current Pharmacology Reports, 6, 103-109. google scholar
  • Lukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., Stanislawek, A. (2021). Breast cancer— epidemiology, risk factors, classification, prognostic markers, and current treatment strategies—an updated review. Cancers, 13(17), 4287. google scholar
  • Mishra, R., Patel, H., Alanazi, S., Yuan, L., Garrett, J. T. (2018). HER3 signaling and targeted therapy in cancer. Oncology Reviews, 12(1), 355. google scholar
  • Muhammad, N., Steele, R., Isbell, T. S., Philips, N., Ray, R. B. (2017). Bitter melon extract inhibits breast cancer growth in preclinical model by inducing autophagic cell death. Oncotarget, 8(39), 66226 66236. google scholar
  • Nagasawa, H., Watanabe, K., Inatomi, H. (2002). Effects of bitter melon (Momordica charantia L.) or ginger rhizome (Zingiber offifinale Rosc) on spontaneous mammary tumorigenesis in shn mice. The American Journal of Chinese Medicine, 30, 195-205. google scholar
  • Nandini, D., Jennifer, A., Pradip, D. (2021). Therapeutic strategies for metastatic triple-negative breast cancers: from negative to positive. Pharmaceuticals, 14(5), 455. google scholar
  • Olivero-Acosta, M., Maldonado-Rojas, W., Olivero-Verbel, J. (2017). Natural products as chemopreventive agents by potential ınhibition of the kinase domain in ErbB receptors. Molecules, 22(2), 308. google scholar
  • Page, B. D. G., Valerie, N. C. K., Wright, R. H. G., Wallner, O., Isaksson, R., Carter, M., Rudd, S. G., Losevsa, O., Jemth ,A. S., Almlöf, I., Font-Mateu, J., Liona-Minguez, S., Baranczewski, P., Jeppsson, F., Homan, E., Almqvist, H., Axelsson, H., Regmi, S., Gustavsson, A. L., Lundback, T., Scobie, M., Strömberg, K., Stenmark, P., Beato, M., Helleday, T. (2018). Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells. Nature Communications, 9(1),250. google scholar
  • Pickup, K. E., Pardow, F., Carbonell-Caballero, J., Lioutas, A., Villanueva-Canas, J. L., Wright, R. H. G., Beato, M. (2019). Expression of oncogenic drivers in 3D cell culture depends on nuclear ATP synthesis by NUDT5. Cancers, 11(9), 1337. google scholar
  • Psilopatis, I., Vrettou, K., Giaginis, C., Theocharis, S. (2023). The Role of bitter melon in breast and gynecological cancer prevention and therapy. International Journal of Molecular Sciences, 24(10), 8918. google scholar
  • Rappe, A. K., Casewit, C. J., Colwell, K. S., Goddard, W. A., III, Skiff, W. M. (1992). UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. Journal of the American Chemical Society, 114(25), 10024-10035. google scholar
  • Ray, R. B., Raychoudhuri, A., Steele, R., Nerurkar, P. (2010). Bitter melon (Momordica charantia) extract ınhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Cancer Research, 70(5), 1925-1931. google scholar
  • Santos, K. B., Guedes, I. A., Karl, A. L. M., Dardenne, L. E. (2020). Highly flexible ligand docking: benchmarking of the dockthor program on the LEADS-PEP protein-peptide data set. Journal of Chemical Information and Modeling, 60(2), 667-683. google scholar
  • Schlam, I., Swain, S. M. (2021). HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now. Npj Breast Cancer, 7(1), 56. google scholar
  • Schöning-Stierand, K., Diedrich, K., Fahrrolfes, R., Flachsenberg, F., Meyder, A., Nittinger, E., Steinegger, R., Rarey, M. (2020). ProteinsPlus: interactive analysis of protein-ligand binding interfaces. Nucleic Acids Research, 48(W1), W48-W53. google scholar
  • Shi, F., Telesco, S. E., Liu, Y., Radhakrishnan, R., Lemmon, M. A. (2010). ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proceedings of the National Academy of Sciences, 107(17), 7692-7697. google scholar
  • Shim, S. H., Sur, S., Steele, R., Albert, C. J., Huang, C., Ford, D. A., Ray, R. B. (2018). Disrupting cholesterol esterification by bitter melon suppresses triple-negative breast cancer cell growth. Molecular Carcinogenesis, 57(11), 1599-1607. google scholar
  • Smolarz, B., Nowak, A. Z., Romanowicz, H. (2022). Breast cancer—epidemiology, classification, pathogenesis and treatment (review of literature). Cancers, 14(10), 2569. google scholar
  • Stamos, J., Sliwkowski, M. X., Eigenbrot, C. (2002). Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. Journal of Biological Chemistry, 277(48), 46265-46272. google scholar
  • Stierand, K., Rarey, M. (2010). Drawing the PDB: protein-ligand complexes in two dimensions. ACS Medicinal Chemistry Letters, 1(9), 540-545. google scholar
  • Sur, S., Ray, R. B. (2020). Bitter melon (Momordica Charantia), a nutraceutical approach for cancer prevention and therapy. Cancers, 12(8), 2064. google scholar
  • Swaminathan, H., Saravanamurali, K., Yadav, S. A. (2023). Extensive review on breast cancer its etiology, progression, prognostic markers, and treatment. Medical Oncology, 40(8), 238. google scholar
  • Tong, C. W. S., Wu, M., Cho, W. C. S., To, K. K. W. (2018). Recent advances in the treatment of breast cancer. Frontiers in Oncology, 8, 227. google scholar
  • Wang, X.-J., Zhou, R.-J., Zhang, N., Jing, Z. (2019). 20(S)-ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy. European Journal of Pharmacology, 850, 141-149. google scholar
  • Wright, R. H. G., Beato, M. (2021). Role of the NUDT enzymes in breast cancer. International Journal of Molecular Sciences, 22(5), 2267. google scholar
  • Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., Yin, M., Zeng, X., Wu, C., Lu, A., Chen, X., Hou, T., Cao, D. (2021). ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Research, 49(W1), W5-W14. google scholar
  • Zhang, Y., Guan, J., Cui, J., Zhao, Y. (2010). Quantitative analysis of aglycone of momordicoside L from Momordica charantia in different areas by HPLC. Zhongguo Zhong yao za zhi= Zhongguo Zhongyao Zazhi= China Journal of Chinese Materia Medica, 35(5), 620-622. google scholar

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APA

Ertik, O. (2024). Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches. International Journal of Environment and Geoinformatics, 11(4), 78-88. https://doi.org/10.26650/ijegeo.1573082


AMA

Ertik O. Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches. International Journal of Environment and Geoinformatics. 2024;11(4):78-88. https://doi.org/10.26650/ijegeo.1573082


ABNT

Ertik, O. Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches. International Journal of Environment and Geoinformatics, [Publisher Location], v. 11, n. 4, p. 78-88, 2024.


Chicago: Author-Date Style

Ertik, Onur,. 2024. “Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches.” International Journal of Environment and Geoinformatics 11, no. 4: 78-88. https://doi.org/10.26650/ijegeo.1573082


Chicago: Humanities Style

Ertik, Onur,. Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches.” International Journal of Environment and Geoinformatics 11, no. 4 (Dec. 2024): 78-88. https://doi.org/10.26650/ijegeo.1573082


Harvard: Australian Style

Ertik, O 2024, 'Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches', International Journal of Environment and Geoinformatics, vol. 11, no. 4, pp. 78-88, viewed 23 Dec. 2024, https://doi.org/10.26650/ijegeo.1573082


Harvard: Author-Date Style

Ertik, O. (2024) ‘Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches’, International Journal of Environment and Geoinformatics, 11(4), pp. 78-88. https://doi.org/10.26650/ijegeo.1573082 (23 Dec. 2024).


MLA

Ertik, Onur,. Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches.” International Journal of Environment and Geoinformatics, vol. 11, no. 4, 2024, pp. 78-88. [Database Container], https://doi.org/10.26650/ijegeo.1573082


Vancouver

Ertik O. Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches. International Journal of Environment and Geoinformatics [Internet]. 23 Dec. 2024 [cited 23 Dec. 2024];11(4):78-88. Available from: https://doi.org/10.26650/ijegeo.1573082 doi: 10.26650/ijegeo.1573082


ISNAD

Ertik, Onur. Momordica charantia (Bitter Melon) Fruit Bioactive Compounds and Potential Inhibitory Effects of Breast Cancer-Related Enzymes: In silico Approaches”. International Journal of Environment and Geoinformatics 11/4 (Dec. 2024): 78-88. https://doi.org/10.26650/ijegeo.1573082



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Gönderim24.10.2024
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