Murraya koenigii extract potential as a herbal alternative therapeutic agent for inhibiting lung cancer cell migration via suppression of MMP-2 and MMP-9 activity

Authors

DOI:

https://doi.org/10.55779/nsb17412725

Keywords:

cancer migration, complementary herbal medicine, matrix metalloproteinase, Murraya koenigii, non-small cell lung cancer

Abstract

Lung cancer, particularly non-small cell lung cancer (NSCLC), is documented as the leading cause of cancer-related deaths worldwide. This is emphasized by the elevated metastatic ability observed in advanced NSCLC cases, a process primarily mediated by increased activity of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9). Interestingly, despite showing no cytotoxicity against the NSCLC cell line, Murraya koenigii demonstrated anti-migratory activity, as indicated by the stagnation of the wound area observed in treated NSCLC cells in vitro. This effect is mediated through the inhibition of MMP-2 and MMP-9 enzymatic activity. Notably, M. koenigii leaf extract exerted this activity at concentrations as low as 14 µg/mL, and increasing the extract concentration did not significantly affect its inhibitory potential. Compound testing and molecular docking further indicated that MMP-9 inhibition was achieved through direct binding between the extract’s high flavonoid content, particularly rutin, and alkaloids with the MMP-9 active site. Despite binding at different residues compared with the known inhibitor, the bioactive compounds, especially mahanine, also exhibited high binding affinity to both MMP-2 and E-cadherin. Overall, the results of this study indicate the potential of M. koenigii leaf extract as an alternative anti-migratory treatment to improve the prognosis of patients with advanced metastatic NSCLC.

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References

Abcam (2025). Gelatin zymography protocol [Online]. Abcam Limited. Retrieved 2025 February 12 from https://www.abcam.com/en-us/technical-resources/protocols/gelatin-zymography

Alfarouk KO, Stock CM, Taylor S, Walsh M, Muddathir AK, Verduzco D, … Rauch C (2015). Resistance to cancer chemotherapy: Failure in drug response from ADME to P-gp. Cancer Cell International 15(1):71. https://doi.org/10.1186/s12935-015-0221-1

Aniqa A, Kaur S, Sadwal S (2022). A review of the anti-cancer potential of Murraya koenigii (Curry Tree) and its active constituents. Nutrition and Cancer 74(1):12-26. https://doi.org/10.1080/01635581.2021.1882509

Armendáriz-Barragán B, Zafar N, Badri W, Galindo-Rodríguez SA, Kabbaj D, Fessi H, Elaissari A (2016). Plant extracts: From encapsulation to application. Expert Opinion on Drug Delivery 13(8):1165-1175. https://doi.org/10.1080/17425247.2016.1182487

Balakrishnan R, Vijayraja D, Jo SH, Ganesan P, Su-Kim I, Choi DK (2020). Medicinal profile, phytochemistry, and pharmacological activities of Murraya koenigii and its primary bioactive compounds. Antioxidants 9(2):101. https://doi.org/10.3390/antiox9020101

Chen S, Shen Z, Gao L, Yu S, Zhang P, Han Z, Kang M (2021). TPM3 mediates epithelial-mesenchymal transition in esophageal cancer via MMP2/MMP9. Annals of Translational Medicine 9(16):1338. https://doi.org/10.21037/atm-21-4043

Chen Y-H, Hsu J-Y, Chu C-T, Chang Y-W, Fan J-R, Yang M-H, Chen H-C (2022). Loss of cell–cell adhesion triggers cell migration through Rac1-dependent ROS generation. Life Science Alliance 6(2): e202201529. https://doi.org/10.26508/lsa.202201529

Civera M, Vasile F, Potenza D, Colombo C, Parente S, Vettraino C, … Belvisi L (2019). Exploring E-cadherin-peptidomimetics interaction using NMR and computational studies. PLoS Computational Biology 15(6):e1007041. https://doi.org/10.1371/journal.pcbi.1007041

Gandalovičová A, Rosel D, Fernandes M, Veselý P, Heneberg P, Čermák V, … Brábek J (2017). Migrastatics—anti-metastatic and anti-invasion drugs: Promises and challenges. Trends in Cancer 3(6):391-406. https://doi.org/10.1016/j.trecan.2017.04.008

Ganeshpurkar A, Saluja AK (2017). The pharmacological potential of rutin. Saudi Pharmaceutical Journal 25(2):149-164. https://doi.org/10.1016/j.jsps.2016.04.025

Graziani V, Rodriguez-Hernandez I, Maiques O, Sanz-Moreno V (2022). The amoeboid state as part of the epithelial-to-mesenchymal transition programme. Trends in Cell Biology 32(3):228-242. https://doi.org/10.1016/j.tcb.2021.10.004

Hawula ZJ, Secondes ES, Wallace DF, Rishi G, Subramaniam VN (2021). The effect of the flavonol rutin on serum and liver iron content in a genetic mouse model of iron overload. Bioscience Reports 41(7):BSR20210720. https://doi.org/10.1042/BSR20210720

Hayun H, Coban M, Bhagat AK, Ozer E, Alfonta L, Caulfield TR, … Papo N (2023). Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14. Scientific Reports 13(1):5186. https://doi.org/10.1038/s41598-023-32019-3

Hobani YH (2022). Cytotoxicity of mahanimbine from curry leaves in human breast cancer cells (MCF-7) via mitochondrial apoptosis and anti-angiogenesis. Molecules 27(3):971. https://doi.org/10.3390/molecules27030971

Hong Y, Park S, Lee MK (2022). The prognosis of non-small cell lung cancer patients according to endobronchial metastatic lesion. Scientific Reports 12(1):13588. https://doi.org/10.1038/s41598-022-17918-1

Ismail A, Noolu B, Gogulothu R, Perugu S, Rajanna A, Babu SK (2016). Cytotoxicity and proteasome inhibition by alkaloid extract from Murraya koenigii leaves in breast cancer cells—molecular docking studies. Journal of Medicinal Food 19(12):1155-1165. https://doi.org/10.1089/jmf.2016.3767

Israelachvili JN (2011). 7-Repulsive steric forces, total intermolecular pair potentials, and liquid structure. Intermolecular and Surface Forces 3:133-149. https://doi.org/10.1016/B978-0-12-375182-9.10007-7

Issa S, Prandina A, Bedel N, Rongved P, Yous S, Borgne ML, Bouaziz Z (2019). Carbazole scaffolds in cancer therapy: a review from 2012 to 2018. Journal of Enzyme Inhibition and Medicinal Chemistry 34(1):1321-1346. https://doi.org/10.1080/14756366.2019.1640692

Jacobs E, Chambin O, Debeaufort F, Benbettaieb N (2023). Synergic versus antagonist effects of rutin on gallic acid or coumarin incorporated into chitosan active films: Impacts on Their release kinetics and antioxidant activity. Antioxidants 12(11):1934. https://doi.org/10.3390/antiox12111934

Jenča A, Mills DK, Ghasemi H, Saberian E, Jenča A, Forood KAM, … Ebrahimifar M (2024). Herbal therapies for cancer treatment: A review of phytotherapeutic efficacy. Biologics: Targets and Therapy 2024(18):229-255. https://doi.org/10.2147/BTT.S484068

Kciuk M, Gielecińska A, Mujwar S, Kołat D, Kałuzińska-Kołat Ż, Celik I, Kontek R (2023). Doxorubicin—an agent with multiple mechanisms of anticancer activity. Cells 12(4):659. https://doi.org/10.3390/cells12040659

Lai-Kee-Him J, Fouillen A, Chee M, Lemercier N, Feracci H, Bron P (2024). Calcium-modulated cis and trans E-cadherin EC1-2 interactions play a key role in formation, dynamics and plasticity of cadherin junctions. bioRxiv 2024.10.14.618140. https://doi.org/10.1101/2024.10.14.618140

Liskova A, Koklesova L, Samec M, Varghese E, Abotaleb M, Samuel SM, … Kubatka P (2020). Implications of flavonoids as potential modulators of cancer neovascularity. Journal of Cancer Research and Clinical Oncology 146(12):3079-3096. https://doi.org/10.1007/s00432-020-03383-8

Liu Y-P, Zheng C-C, Huang Y-N, He M-L, Xu W-W, Li B (2021). Molecular mechanisms of chemo- and radiotherapy resistance and the potential implications for cancer treatment. MedComm 2(3):315-340. https://doi.org/10.1002/mco2.55

López-Camacho E, García-Godoy MJ, García-Nieto J, Nebro AJ, Aldana-Montes JF (2016). A new multi-objective approach for molecular docking based on RMSD and binding energy. In: International Conference on Algorithms for Computational Biology. Cham: Springer International Publishing 9702:65-77. https://doi.org/10.1007/978-3-319-38827-4_6

Malacaria L, Corrente GA, Beneduci A, Furia E, Marino T, Mazzone G (2021). A review on coordination properties of Al(III) and Fe(III) toward natural antioxidant molecules: Experimental and theoretical insights. Molecules 26(9):2603. https://doi.org/10.3390/molecules26092603

Mcbride JM, Eckmann J-P, Tlusty T (2022). General theory of specific binding: Insights from a genetic-mechano-chemical protein model. Molecular Biology and Evolution 39(11):msac217. https://doi.org/10.1093/molbev/msac217

Mojodi E, Doostabadi MR, Sabbagh SK, Mohammadpanah M, Haghiralsadat BF, Maleki B (2022). Cell Toxicity effect of the extract of medicinal plants against human breast (MCF7 and KBR3) cancer cell lines. Gene Cell Tissue 10(1):e119837. https://doi.org/10.5812/gct-119837

Nagori M, Rajput D, Choudhary G, Khabiya R (2025). Qualitative and quantitative methods of phytochemical analysis. Pharmacognosy and Phytochemistry: Principles, Techniques, and Clinical Applications 8:143-166. https://doi.org/10.1002/9781394203680.ch08

Nandy SK, Das S (2023). Unveiling the diverse medicinal properties of Murraya koenigii. Sciences of Phytochemistry 2(2):211-225. https://doi.org/10.58920/sciphy02020107

Ogut D, Reel B, Korkmaz CG, Arun MZ, Micili SC, Ergur BU (2016). Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells. Folia Histochemica et Cytobiologica 54(4):171-180. https://doi.org/10.5603/FHC.a2016.0022

Perlikos F, Harrington KJ, Syrigos KN (2013). Key molecular mechanisms in lung cancer invasion and metastasis: a comprehensive review. Critical Reviews in Oncology/Hematology 87(1):1-11. https://doi.org/10.1016/j.critrevonc.2012.12.007

Popper HH (2016). Progression and metastasis of lung cancer. Cancer and Metastasis Reviews 35(1):75-91. https://doi.org/10.1007/s10555-016-9618-0

Rutkowska M, Olszewska MA, Kolodziejczyk-Czepas J, Nowak P, Owczarek A (2019). Sorbus domestica leaf extracts and their activity markers: Antioxidant potential and synergy effects in scavenging assays of multiple oxidants. Molecules 24(12):2289. https://doi.org/10.3390/molecules24122289

Sachan P, Shrivastava P, Kushwaha A, Jain K, Kant L (2025). A deep dive into the phytochemical composition of Murraya koenigii (curry leaf): Active compounds and their therapeutic implications. Bütünleyici ve Anadolu Tıbbı Dergisi 6(1):40-59. https://doi.org/10.53445/batd.1581503

Salamah N, Ningsih DS (2017). Total alkaloid content in various fractions of Tabernaemonata sphaerocarpa Bl. (Jembirit) leaves. IOP Conference Series: Materials Science and Engineering. IOP Publishing 259(1):012017. https://doi.org/10.1088/1757-899X/259/1/012017

Shaikh JR, Patil MK (2020). Qualitative tests for preliminary phytochemical screening: An overview. International Journal of Chemical Studies 8(2):603-608. https://doi.org/10.22271/chemi.2020.v8.i2i.8834

Siahaan P, Prasasty VD, Manna A, Hudiyanti D (2018). Interaction studies between cyclic peptide ADT-C3 (Ac-CADTPC-NH2) with E-cadherin protein using the molecular docking method simulated on 120ns. Jurnal Kimia Sains dan Aplikasi 21(2):85-91. https://doi.org/10.14710/jksa.21.2.85-91

Sowemimo M, Adeniyi A (2023). Synthesis and characterization of alkaloid derived hydrazones and their metal (II) complexes. Physical Sciences Reviews 8(11):4085-4098. https://doi.org/10.1515/psr-2021-0163

Sung H, Ferlay J, Siegel RL, 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

Supasena W, Muangnoi C, Praengam K, Wong TW, Qiu G, Ye S, … Rojsitthisak P (2020). Enhanced selective cytotoxicity of doxorubicin to breast cancer cells by methoxypolyethylene glycol conjugation via a novel beta-thiopropanamide linker. European Polymer Journal 141:e110056. https://doi.org/10.1016/j.eurpolymj.2020.110056

Tayo LL, Aquino AC, Pasamba EC (2022). Molecular docking studies on the binding affinity of alpha-conotoxins on voltage-gated sodium ion channel using an incremental genetic algorithm approach. International Conference on Chemical Science and Engineering. Singapore: Springer Nature Singapore 21:81-87. https://doi.org/10.1007/978-981-19-4290-7_10

Viteritti E, Oliva E, Eugelio F, Fanti F, Palmieri S, Bafile E, … Sergi M (2022). Analysis of carbazole alkaloids in Murraya koenigii by means of high performance liquid chromatography coupled to Tandem mass spectrometry with a predictive multi experiment approach. Journal of Chromatography Open 2:e100055. https://doi.org/10.1016/j.jcoa.2022.100055

Weiss F, Lauffenburger D, Friedl P (2022). Towards targeting of shared mechanisms of cancer metastasis and therapy resistance. Nature Reviews Cancer 22(3):157-173. https://doi.org/10.1038/s41568-021-00427-0

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Published

2025-12-04

How to Cite

DEARYZA, S., TANOTO, J. P. W., SUBRATA, M. A., FEBRIAN, T., WIBOWO, K. M., TJOA, O., MICHAEL, M., ALEXIA, N., & KRISTIANI, L. (2025). Murraya koenigii extract potential as a herbal alternative therapeutic agent for inhibiting lung cancer cell migration via suppression of MMP-2 and MMP-9 activity. Notulae Scientia Biologicae, 17(4), 12725. https://doi.org/10.55779/nsb17412725

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Research articles
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DOI: 10.55779/nsb17412725

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