Anticancer Activity from Stem Bark of Nauclea subdita Nanoliposomes Extract on MCF-7 Breast Cancer Cells: In vitro and In silico Study
Abstract
Breast cancer caused many deaths in Indonesia in 2022, and although chemotherapy is commonly used for treatment, it often leads to serious side effects. Natural alternatives such as Bangkal (Nauclea subdita), which contains alkaloids with potential anticancer properties, may offer milder side effects. Studies have shown that Bangkal (Nauclea subdita) stem bark extract can inhibit the growth of cancer cells like LNCaP and PC-3. However, natural compounds usually face challenges such as low bioavailability and poor solubility, which can limit their effectiveness. This study investigates alkaloids in Bangkal (Nauclea subdita) stem bark as anti-breast cancer agents targeting MCF-7 cells and develops them into nanoliposome form to improve their effectiveness. A total of 960 grams of Bangkal (Nauclea subdita) stem bark powder was macerated with n-hexane, followed by dichloromethane extraction after being treated with ammonia solution. The extracts were analyzed using LC-MS. Nanoliposomes were prepared via thin-layer hydration and characterized using PSA. In vitro tests included MTT and co-combination assays, while molecular docking was used for in silico analysis. Results indicate that the alkaloids atropine, funtumine, vasicinol, oxymatrine, and evodiamine effectively inhibit Bcl-2 protein expression more than HER2. The optimal nanoliposome formula (F3) had a particle size of 148 nm, PDI of 0.673, and zeta potential of -41.3. The IC₅₀ value of the crude extract (361.5 μg/mL), initially categorized as weak, improved to a moderate level (188.18 μg/mL) after formulation into a nanoliposome preparation. These findings indicate that Bangkal (Nauclea subdita) stem bark can be developed into a nanoliposome formulation and shows potential as an anticancer agent based on both in vitro and in silico studies.
Keywords: Nauclea subdita, alkaloids, nanoliposome, breast cancer, MCF-7.
Full Text:
PDFReferences
Ahmed, E.A., Alkuwayti, M.A., and Ibrahim, H.I.M., 2022, Atropine is a suppressor of epithelial–mesenchymal transition (EMT) that reduces stemness in drug-resistant breast cancer cells, International Journal of Molecular Sciences, 23(17), 9849.
Badmus, J.A., Ekpo, O.E., Sharma, J.R., Sibuyi, N.R.S., Meyer, M., Hussein, A.A., et al., 2020, An insight into the mechanism of holamine-and funtumine-induced cell death in cancer cells, Molecules, 25(23), 5716.
Dela Cruz, J.M.D., Dones, S.A.A., Villanueva, R.C., Labrador, A.M., and Santiago-Bautista, M.R., 2022, Molecular docking and in silico pharmacological screening of oleosin from Cocos nucifera complexed with tamoxifen in developing potential breast chemotherapeutic leads, Asian Pacific Journal of Cancer Prevention, 23(7), 2421–2430.
Deswita, N.A., 2023, Deteksi kanker payudara pada remaja dan wanita dewasa serta pencegahannya. Penerbit Adab.
Ghasemi, M., Turnbull, T., Sebastian, S., and Kempson, I., 2021, The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis, International Journal of Molecular Sciences, 22(23), 12827.
Hajrulai-Musliu, Z., Uzunov, R., Jovanov, S., Jankuloski, D., Stojkovski, V., Pendovski, L., et al., 2022, Development of a new LC–MS/MS method for multiple residues/contaminants in bovine meat, BMC Chemistry, 5, 52–82.
Harmita, K., Harahap, Y., and Supandi, 2019, Liquid chromatography–tandem mass spectrometry (LC-MS/MS), ISFI Penerbitan.
Kumar, S., Singh, R., Dutta, D., Chandel, S., Bhattacharya, A., Ravichandiran, V., et al., 2022, In vitro anticancer activity of methanolic extract of Justicia adhatoda leaves with special emphasis on human breast cancer cell line, Molecules, 27(23), 8222.
Li, H., Zhang, C., Zhang, M., Yao, Q., Yang, H., Fan, L., et al., 2020, Angustoline inhibited esophageal tumors through regulating LKB1/AMPK/ELAVL1/LPACT2 pathway and phospholipid remodeling, Frontiers in Oncology, 10.
Li, L., Zhang, C., Huang, C., Tian, X., Sun, W., and Jiang, S., 2022, Research advances in antitumor mechanism of evodiamine, Journal of Chemistry, 2022, 12784257.
Li, X., Sun, J., Xu, Q., Duan, W., Yang, L., Wu, X., et al., 2020, Oxymatrine inhibits colorectal cancer metastasis via attenuating PKM2-mediated aerobic glycolysis, Cancer Management and Research, 12, 9503–9513.
Liew, S.Y., Looi, C.Y., Paydar, M., Cheah, F.K., Leong, K.H., Wong, W.F., et al., 2014, Subditine, a new monoterpenoid indole alkaloid from bark of Nauclea subdita (Korth.) Steud. induces apoptosis in human prostate cancer cells, PLOS ONE, 9(2), e87286.
Listiyana, A., Mutiah, R., Suyadinata, A., and Salsabilla, F.R., 2020, Pengembangan sistem nanostructured lipid carrier (NLC) daun Chrysanthemum cinerariifolium dengan variasi konsentrasi lipid, Journal of Islamic Medicine, 4(2), 86–97.
Loh, J.S., Tan, L.K.S., Lee, W.L., Ming, L.C., How, C.W., Foo, J.B., et al., 2021, Do lipid-based nanoparticles hold promise for advancing the clinical translation of anticancer alkaloids?, Cancers, 13(21), 5346.
Millan-Casarrubias, E.J., García-Tejeda, Y.V., González-De la Rosa, C.H., Ruiz-Mazón, L., Hernández-Rodríguez, Y.M., and Cigarroa- Mayorga, O.E., 2025, Molecular docking and pharmacological in silico evaluation of camptothecin and related ligands as promising HER2-targeted therapies for breast cancer, Current Issues in Molecular Biology, 47(3), 193.
Németh, Z., Csóka, I., Jazani, R.S., Sipos, B., Haspel, H., Kozma, G., Kónya, Z., and Dobó, D.G., 2022, Quality by design-driven zeta potential optimisation study of liposomes with charge imparting membrane additives, Pharmaceutics, 14(9), 1798.
Preuer, K., Lewis, R.P.I., Hochreiter, S., Bender, A., Bulusu, K.C., and Klambauer, G., 2017, DeepSynergy: Predicting anti-cancer drug synergy with deep learning, Bioinformatics, 34(9), 1538–1546.
Putra, P.P., 2022, Teori dan tutorial molecular docking menggunakan AutoDock Vina. Wawasan Ilmu.
Rønneberg, L., Kirk, P.D.W., and Zucknick, M., 2023, Dose–response prediction for in-vitro drug combination datasets: A probabilistic approach, BMC Bioinformatics, 24, 161.
Rudolph, J., Settleman, J., and Malek, S., 2021, Emerging trends in cancer drug discovery—from drugging the “undruggable” to overcoming resistance, Cancer Discovery, 11(4), 815–821.
Susilo, A., Cahyati, M., Pranowo, D., Nurjannah, N., Masyithoh, D., Awwaly, K.U.A., et al., 2023, Simulasi molekuler pada bidang pangan fungsional: Prinsip dasar dan tutorial.
Tilsed, C.M., Fisher, S.A., Nowak, A.K., Lake, R.A., and Lesterhuis, W.J., 2022, Cancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action, Frontiers in Oncology, 12, 960317.
WHO, 2022, Cancer, https://www.who.int/health-topics/cancer#tab=tab_1, Accessed on December 22nd, 2023.
DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev16iss3pp182-196
Copyright (c) 2025 Indonesian Journal of Cancer Chemoprevention
Indexed by:
Indonesian Society for Cancer Chemoprevention
