Moringa oleifera Leaves Ethanol Extract Inhibits HT-29 Cells and COX-2 Expression Predictably Through PPARγ Activation

https://doi.org/10.22146/mot.89037

Aryo Tedjo(1*), Ifana Aprilliyani(2), Kusmardi Kusmardi(3), Ajeng Megawati(4), Dimas Ramadhian Noor(5)

(1) *) Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, DKI Jakarta *) Drug Development Research Cluster, Faculty of Medicine, Universitas Indonesia, Jakarta
(2) Undergraduate Program, Faculty of Medicine, Universitas Indonesia, Jakarta, DKI Jakarta
(3) *) Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, DKI Jakarta *) Human Cancer Research Center, Indonesia Medical Education and Research Institute Faculty of Medicine, Universitas Indonesia, Jakarta, DKI Jakarta
(4) Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, DKI Jakarta
(5) Human Cancer Research Center, Indonesia Medical Education and Research Institute Faculty of Medicine, Universitas Indonesia, Jakarta, DKI Jakarta
(*) Corresponding Author

Abstract


Colorectal cancer is the second leading cause of death among all cancer cases worldwide. Cancer cells often exhibit overexpression of cyclooxygenase-2 (COX-2), producing prostaglandin E2 (PEG2) and subsequent inflammation and neoplasia. Moringa oleifera is rich in bioactive compounds such as polyphenols, flavonoids, and saponins, known for their anti-inflammatory and antioxidant properties. This study aimed to investigate the inhibitory effects of M. oleifera leaves ethanol extract on COX-2 expression in HT-29 cells. Dried M. oleifera leaves (5 g) were ethanol-macerated for 24 hours, yielding a 10 mg ethanol extract. MTT inhibition is used for immunocytochemistry evaluation of COX-2 expression. Molecular docking of phenolic compounds from the extract on PPARγ indicated an agonistic potential. The ethanol extract of M. oleifera leaves demonstrated anticancer activity with an IC50 value of 114.8 µg/ml, with a significant reduction in COX-2 expression observed at a dose of 100 ppm, resulting in an H-score of 111.83 ± 2.21. Peroxisome proliferator-activated receptor-gamma (PPARγ) activity is thought to be the first step in suppressing COX-2 expression. Three phenolic compounds found in M. oleifera are predicted to be PPARγ agonists: rutin, naringin, and hesperidin, according to the molecular docking simulations.


Keywords


colorectal cancer; COX-2 expression; Moringa oleifera; PPARγ agonists

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References

Arnold, S. V, Inzucchi, S. E., Echouffo-Tcheugui, J. B., Tang, F., Lam, C. S. P., Sperling, L. S., & Kosiborod, M. (2019). Understanding Contemporary Use of Thiazolidinediones. Circulation. Heart Failure, 12(6), e005855. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005855

Arya, N., & Kaur, Dr. A. (2022). Molecular Docking: A Review Paper. International Journal of Innovative Research in Engineering & Management, 140–146. https://doi.org/10.55524/ijirem.2022.9.1.25

Bitencourt-Ferreira, G., & de Azevedo, W. F. (2019). Molegro Virtual Docker for Docking. Methods in Molecular Biology (Clifton, N.J.), 2053, 149–167. https://doi.org/10.1007/978-1-4939-9752-7_10

Chelliah, R., & Oh, D.-H. (2022). Screening for Anticancer Activity: 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium (MTT) Assay (pp. 423–425). https://doi.org/10.1007/978-1-0716-1728-1_54

Desai, S. J., Prickril, B., & Rasooly, A. (2018). Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer. Nutrition and Cancer, 70(3), 350–375. https://doi.org/10.1080/01635581.2018.1446091

Global Cancer Observatory: Cancer Today. Indonesia Fact Sheet. Lyon, France: International Agency for Research on Cancer; 2020. (n.d.). Retrieved November 17, 2023, from https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf

Hanifah, R., Novitarani, N., Harmen, F., Tedjo, A., Azizah, N., Putrianingsih, R., Fachri, W., & Kusmardi, K. (2019). The Inhibition of Ethanol Extract of Phaleria macrocarpa Stem Bark on COX-2 Expression of HCT116 Colorectal Cancer Cell Line. Research Journal of Pharmacy and Technology, 12, 2902. https://doi.org/10.5958/0974-360X.2019.00489.X

Hashemi Goradel, N., Najafi, M., Salehi, E., Farhood, B., & Mortezaee, K. (2019). Cyclooxygenase-2 in cancer: A review. Journal of Cellular Physiology, 234(5), 5683–5699. https://doi.org/10.1002/jcp.27411

Ibrahim, N. I., Shamsudin, S. H., Lee, S. K., & T. Sharif, S. E. (2023). Prognostic significance of Cyclooxygenase-2 expression in colorectal adenoma and Adenocarcinoma: A clinicopathologic study. Human Pathology Reports, 31, 300692. https://doi.org/10.1016/j.hpr.2023.300692

Kadhum, R., Abbas, M. K., & Madlum, K. N. (2022). Aspirin and celecoxib revealed anticancer and immunomodulatory effects on colon cancer cells. International Journal of Health Sciences, 13527–13535. https://doi.org/10.53730/ijhs.v6nS1.8380

Kim, S., Thiessen, P. A., Bolton, E. E., Chen, J., Fu, G., Gindulyte, A., Han, L., He, J., He, S., Shoemaker, B. A., Wang, J., Yu, B., Zhang, J., & Bryant, S. H. (2016). PubChem Substance and Compound databases. Nucleic Acids Research, 44(D1), D1202-13. https://doi.org/10.1093/nar/gkv951

Kou, X., Li, B., Olayanju, J. B., Drake, J. M., & Chen, N. (2018). Nutraceutical or Pharmacological Potential of Moringa oleifera Lam. Nutrients, 10(3). https://doi.org/10.3390/nu10030343

Kuroda, M., Mimaki, Y., Honda, S., Tanaka, H., Yokota, S., & Mae, T. (2010). Phenolics from Glycyrrhiza glabra roots and their PPAR-gamma ligand-binding activity. Bioorganic & Medicinal Chemistry, 18(2), 962–70. https://doi.org/10.1016/j.bmc.2009.11.027

Kusmiyati, K., Keman, S., Amin, M., Suwarno, S., & Rahmawati, I. (2018). Phytochemical Compounds Found In Moringa (Moringa Oleifera) Leaves Ethanol Extract From Kupang, East Nusa Tenggara. Proceeding 1st. International Conference Health Polytechnic of Kupang, 184–189. https://proceeding.poltekeskupang.ac.id/index.php/ichpk/article/view/48

Lin, Y., Lu, C., Hsiang, Y., Pi, S., Chen, C., Cheng, K., Pan, H., Chien, P., & Chen, Y. (2019). c‐Met inhibition is required for the celecoxib‐attenuated stemness property of human colorectal cancer cells. Journal of Cellular Physiology, 234(7), 10336–10344. https://doi.org/10.1002/jcp.27701

Molegro ApS. (2011). Molegro Virtual Docker User Manual. Høegh-Guldbergs Gade 10, Building 1090 DK-8000 Aarhus C Denmark.

Muhammed, M. T., & Aki-Yalcin, E. (2024). Molecular Docking: Principles, Advances, and Its Applications in Drug Discovery. Letters in Drug Design & Discovery, 21(3), 480–495. https://doi.org/10.2174/1570180819666220922103109

Osman, A., & El-Sobki, A. (2019). Insecticidal Activity and Chemical Composition of Moringa oleifera Extract Against The Leguminous Aphid, Aphis craccivora Koch on Broad Bean Plants. Journal of Plant Protection and Pathology, 10, 567–571. https://doi.org/10.21608/jppp.2019.77958

Parris, T. Z., Aziz, L., Kovács, A., Hajizadeh, S., Nemes, S., Semaan, M., Chen, C. Y., Karlsson, P., & Helou, K. (2014). Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma. BMC Cancer, 14, 324. https://doi.org/10.1186/1471-2407-14-324

Pottoo, F. H., Ibrahim, A. M., Alammar, A., Alsinan, R., Aleid, M., Alshehhi, A., Alshehri, M., Mishra, S., & Alhajri, N. (2022). Thymoquinone: Review of Its Potential in the Treatment of Neurological Diseases. Pharmaceuticals (Basel, Switzerland), 15(4). https://doi.org/10.3390/ph15040408

Sander, T., Freyss, J., von Korff, M., & Rufener, C. (2015). DataWarrior: An Open-Source Program For Chemistry Aware Data Visualization And Analysis. Journal of Chemical Information and Modeling, 55(2), 460–473. https://doi.org/10.1021/ci500588j

Sheng, J., Sun, H., Yu, F.-B., Li, B., Zhang, Y., & Zhu, Y.-T. (2020). The Role of Cyclooxygenase-2 in Colorectal Cancer. International Journal of Medical Sciences, 17(8), 1095–1101. https://doi.org/10.7150/ijms.44439

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660

Thanan, R., Murata, M., Ma, N., Hammam, O., Wishahi, M., El Leithy, T., Hiraku, Y., Oikawa, S., & Kawanishi, S. (2012). Nuclear localization of COX-2 in relation to the expression of stemness markers in urinary bladder cancer. Mediators of Inflammation, 2012, 165879. https://doi.org/10.1155/2012/165879

Varghese, F., Bukhari, A. B., Malhotra, R., & De, A. (2014). IHC Profiler: An Open Source Plugin for the Quantitative Evaluation and Automated Scoring of Immunohistochemistry Images of Human Tissue Samples. PLoS ONE, 9(5), e96801. https://doi.org/10.1371/journal.pone.0096801

Venkataraman, B., Almarzooqi, S., Raj, V., Alhassani, A. T., Alhassani, A. S., Ahmed, K. J., Subramanian, V. S., Ojha, S. K., Attoub, S., Adrian, T. E., & Subramanya, S. B. (2021). Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor. Nutrients, 13(4). https://doi.org/10.3390/nu13041343

Vergara-Jimenez, M., Almatrafi, M. M., & Fernandez, M. L. (2017). Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease. Antioxidants (Basel, Switzerland), 6(4). https://doi.org/10.3390/antiox6040091

Xu, L., Che, S., Chen, H., Liu, Q., Shi, J., Jin, J., & Hou, Y. (2023). PPARγ agonist inhibits c‐Myc‐mediated colorectal cancer tumor immune escape. Journal of Cellular Biochemistry, 124(8), 1145–1154. https://doi.org/10.1002/jcb.30437

Zhang, Z., Ghosh, A., Connolly, P. J., King, P., Wilde, T., Wang, J., Dong, Y., Li, X., Liao, D., Chen, H., Tian, G., Suarez, J., Bonnette, W. G., Pande, V., Diloreto, K. A., Shi, Y., Patel, S., Pietrak, B., Szewczuk, L., … Evans, D. C. (2021). Gut-Restricted Selective Cyclooxygenase-2 (COX-2) Inhibitors for Chemoprevention of Colorectal Cancer. Journal of Medicinal Chemistry, 64(15), 11570–11596. https://doi.org/10.1021/acs.jmedchem.1c00890



DOI: https://doi.org/10.22146/mot.89037

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