Co-Chemotherapy Effect of Glycosylated Nanoalbumin Genitri Seed Extract Targeting Induced Apoptotic on Overexpressed HER2+ Breast Cancer
Abstract
HER2-targeted therapy aims to stop proliferation and induced apoptosis. Genitri seeds show anticancer effects and have potential as co-chemotherapy. To maximize bioactive delivery, a glycosylated-nanoalbumin delivery system is used. This research aims to explore the ability of Glycosylated-Nanoalbumin Genitri Seeds (GN-GSE) to induce apoptosis in MCF-7/HER2 cancer cells. The cytotoxic test using the MTT assay showed GSE selectivity (SI=2.7) against cancer cells (IC50 104 μg/mL) and non-toxicity against normal cells (IC50 284 μg/mL). Induction of apoptosis occurs through inhibition of the CDK1 protein which is predicted by molecular docking. GSE has the potential as a synergistic co-chemotherapy with tamoxifen (CI<1) and has good affinity for the CDK1 inhibitory domain. Elaeocarpenine is known to have good affinity with a greater ΔG value (-11.40 kcal/mol) than the native ligand. The GN-GSE formula meets the criteria for nanoparticles with good stability. This research shows that GSE has anti-cancer activity, making it potential as a therapy for HER2 overexpressed breast cancer as well as in a glycosylated nanoalbumin drug delivery system.
Keywords: Apoptotic induced, co-chemotherapy, genitri seeds, glycosylated, nanoalbumin.
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Aguilar-Hernández, G., Zepeda-Vallejo, L.G., García-Magaña, M.d.L., Vivar-Vera, M.d.l.Á., Pérez-Larios, A., Girón-Pérez, M.I., et al., 2020, Extraction of Alkaloids Using Ultrasound from Pulp and By-Products of Soursop Fruit (Annona muricata L.), Applied Sciences, 10(14), 4869. CrossRef
Amtiria, R., and Berawi, K.N., 2018, Peran Human Epidermal Growth Factor Receptor-2 pada Kanker Payudara, J.Agromedicine Unila, 5(2), 644-647. Link
Artun, F.T., Karagoz, A., Ozcan, G., Melikoglu, G., Anil, S., Kultur, S., and Sutlupinar, N., 2016, In vitro anticancer and cytotoxic activities of some plant extracts on HeLa and Vero cell lines, JBUON, 21(3), 720-725. CrossRef
Asyhari, M.H., Palupi, N.S., and Faridah, D.N., 2018, Karakteristik Kimia Konjugat Isolat Protein Kedelai-Laktosa yang Berpotensi dalam Penurunan Alergenisitas, Jurnal Teknologi dan Industri Pangan, 29(1), 39-48. CrossRef
Berteau, C., Filipe-Santos, O., Wang, T., Rojas, H.E., Granger, C., and Schwarzenbach, F., 2015, Evaluation of the Impact of Viscosity, injection Volume, and Injection flow rate on subcutaneous injection tolerance, Medical Devices: Evidence and Research, 8, 473-484. CrossRef
Bose, R., and Ma, C.X., 2021, Breast cancer, HER2 mutations, and overcoming drug resistance, Journal of Medicine, 385(13), 1241-1243.
Chairunnisa S, Wartini, N.M., and Suhendra L., 2019, Pengaruh Suhu dan Waktu Maserasi terhadap Karakteristik Ekstrak Daun Bidara (Ziziphus mauritiana L.) sebagai Sumber Saponin, Jurnal Rekayasa dan Manajemen Agroindustri, 7(4), 551. CrossRef
Chandrashekar, D.S., Karthikeyan, S.K., Korla, P.K., Patel, H., Shovon, A.R., Athar, M., et al., 2022, UALCAN: An update to the integrated cancer data analysis platform, Neoplasia, 25, 18-27. CrossRef
Costa, A.F., Campos, D., Reis, C.A., and Gomes, C., 2020, Targeting Glycosylation: A New Road for Cancer Drug Discovery, Trends Cancer., 6(9), 757-766. CrossRef
Emilda, and Delfira, N., 2023, Pemanfaatan Silika Gel 70-230 Mesh Bekas Sebagai Pengganti Fase Diam Kromatografi Kolom pada Praktikum Kimia Organik, Indonesian Journal of Laboratory, 6(1), 45-51. CrossRef
Fonte, P., Reis, S., and Sarmento, B., 2016, Facts and Evidence on the Lyophilization of Polymeric Nanoparticle for Drug Delivery, Journal of Control Release, 225, 75-86. CrossRef
GCO, 2020, Global Cancer Observatory: Indonesia Fact Sheet, Jenewa: International Agency for Research on Cancer.
Gowthama, P.U., Baskar, R., Kumaresan, K., and Poorani, G., 2020, Investigations into the phytochemical profile in the seeds of Elaeocarpus variabilis fruits: A potential untapped source endemic to Western Ghats, Journal of Pharmacognosy and Phytochemistry, 9(4), 566–571. CrossRef
Haagensen, E.J., Kyle, S., Beale, G.S., Maxwell, R.J., and Newell, D.R., 2012, The Synergistic Interaction of MEK and PI3K Inhibitors is Modulated by mTOR Inhibition, British Journal of Cancer, 106, 1386–1394. CrossRef
Hikmawanti, 2023, Phenolics and Flavonoids Content of Wijaya Kusuma Leaves Fractions using Micro-plate Based Assay, Indonesian Journal of Pharmaceutical Science and Technology, 10(1), 45-51. CrossRef
Ho, W.Y., Liew, S.S., Yeap, S.K., and Alitheen, N.B, 2021, Synergistic Cytotoxicity between Elephantopus scaber and Tamoxifen on MCF-7-Derived Multicellular Tumor Spheroid, Evidence-Based Complementary and Alternative Medicine, 2021, 6355236. CrossRef
Huang, Y., Hu, L., Huang, S., Xu, W., Wan, J.,Wang, D., et al., 2018, Curcumin-loaded Galactosylated BSA Nanoparticles as Targeted Drug Delivery Carriers Inhibit Hepatocellular Carcinoma Cell Proliferation and Migration, International Journal of Nanomedicine, 13, 8309-8323. CrossRef
Ikawati, M., Jenie, R.I., Utomo, R.Y., Amalina, N.D., Ilmawati, G.P.N., Kawaichi, M., and Meiyanto, E., 2020, Genistein enhances cytotoxic and antimigratory activities of doxorubicin on 4T1 breast cancer cells through cell cycle arrest and ROS generation, J. of Applied Pharm. Sci., 10(10), 095-104. CrossRef
Koppenol, W.H., Bounds, P.L., and Dang, C.V., 2011, Otto Warburg’s Contribution to Current Concepts of Cancer Metabolism, Nature Reviews cancer, 11(5), 325-337. CrossRef
Lestari, B., dan Utomo, R.Y., 2022., CEP55 Inhibitor: Extensive Computational Approach Defining A New Target Of Cell Cycle Machinery Agent, Adv. Pharm. Bull., 12(1), 191-199. CrossRef
Li, J., Chen, T., Deng, F., Wan, J., Tang, Y., Yuan, P., and Zhang, L., 2015, Synthesis, Characterization, and In Vitro Evaluation of Curcumin-loaded Albumin Nanoparticles Surfacefunctionalized with Glycyrrhetinic Acid, Int J Nanomedicine., 10, 475–487. CrossRef
Mahajanakatti, A.B., Deepak, T.S., Achar, R.R., Pradeep, S., Prasad, S.K., Narayanappa, R., et al., 2022, Nanoconjugate Synthesis of Elaeocarpus ganitrus and the Assessment of Its Antimicrobial and Antiproliferative Properties, Molecules, 27(8), 2442. CrossRef
Martinez-Saez, O., and Prat, A., 2021, Current and Future Management of HER2-Positive Metastatic Breast Cancer, JCO Oncology Practice, 17(10), 594-604. CrossRef
Masadi, Y.I., Lestari, T., and Dewi, I.K., 2018, Identifikasi Kualitatif Senyawa terpenoid Ekstrak N-heksana Sediaan Losion daun Jerut Purut (Citrus Hystrix Dc), Jurnal Kebidanan dan Kesehatan Tradisional, 3(1), 32-40. CrossRef
Novitasari, D., Nakamae, I., Jenie, R.I., Kato, N.Y., Kato, J.Y., and Meiyanto, E., 2023, Pentagamavunone-1 Inhibits Aggresive Breast Cancer Cell Proliveration Through Mitotic Catasthrope and ROS-Mediated Activities: In Vitro and In Vivo Studies, Saudi Pharmaceutical Journal, 32(1), 101892. CrossRef
Ortiz, C.L.D., Completo, G.C., Nacario, R.C., and Nellas, R.B., 2019, Potential inhibitors of galactofuranosyltransferase 2 (GlfT2): molecular docking, 3DQSAR, and In Silico ADMETox Studies, Scientific Reports, 9(1), 17096. CrossRef
Primiani, C.N., Pujiati, and Setiawan, M.A., 2022, Bioactive Compounds Profile of Alkaloid on Elaeocarpus sphaericus Schum Seeds by Liquid Chromatography-Mass Spectrometry, Advances in Social Science, Education and Humanities Research, 630, 120-125. CrossRef
PubChem, 2025, Compound Summary for CID 16747727, Elaeocarpenine. https://pubchem. ncbi.nlm.nih.gov/compound/Elaeocarpenine#section=Chemical-and-Physical-Properties [accessed on 25 May 2025]
Saatci, O., Borgoni, S., Akbulut, O., Durmus S., Raza, U., Eyupoglu, E., et al., 2018, Targeting PLK1 overcomes T-DM1 resistance via CDK1-dependent phosphorylation and inactivation of Bcl-2/ xL in HER2-positive breast cancer, Oncogene, 37(17), 2251-2269. CrossRef
Siddiqa, A., Long, L.M., Li, L., Marciniak, R.A., and Kazhdan, I., 2008, Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins Survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways, BMC Cancer, 8, 129. CrossRef
Suseno, R., Palupi, N.S., and Prangdimurti, E., 2015, Alergenisitas Sistem Glikasi Isolat Protein Kedelai-Fruktooligosakarida, agriTECH, 36(4), 450-459. CrossRef
Verma, D., Gulati, N., Kaul, S., Mukherjee, S., and Nagaich, U., 2018, Protein Based Nanostructures for drug Delivery, Journal of Pharmaceutics, 9285854. CrossRef
Veronika, D., 2015, Foumulasi Tablet Hisap Nanopartikel Daun Sirih Merah (Piper crocotum Ruiz dan Pav) Secara Granulasi Basah, Tesis, Fak. Farm. Univ. Sumatra Utara Medan.
Vinay, S.P., Udayabhanu, Sumedha, H.N., Shashank, M., Nagaraju, G., and Chandrasekhar, N., 2021, In-vitro antibacterial, antioxidant and cytotoxic potential of gold nanoparticles synthesized using novel Elaeocarpus ganitrus seeds extract, Advanced Material and Device, 6(1), 127-133. CrossRef
Wijnen, R., Pecoraro, C., Carbone, D., Fiuji, H., Avan, A., Peters, G.J., Giovannetti, E., and Diana, P., 2021, Cyclin Dependent Kinase-1 (CDK-1) Inhibition as a Novel Therapeutic Strategy against Pancreatic Ductal Adenocarcinoma (PDAC), Cancers (Basel), 13(4389), 1-18. CrossRef
Yogesh, G., Sapan, S., Shailju, G., Manjusha, Y., and Dinesh, C., 2017, Update and Revieew on Elaeocarpus: Its Botanical, Medicinal, Pharmacological and Therapeutic Profile, Journal of Medical Pharmaceutical and Allied Sciences, 6(01), 812-826. Link
Zhou, X., Qin, X., Gong, T., Zang, Z., and Fu, Y., 2017, d-fructose modification enhanced internalization of mixed micelles in breast cancer cells via GLUT5 transporters, Macromol, Biosci., 17(7). CrossRef
Zulfin, U.M., Rahman, A., Hanifa, M., Utomo, R.Y., and Meiyanto, E., 2021, Reactive oxygen species and senescence modulatory effects of rice bran extract on 4T1 and NIH-3T3 cells co-treatment with doxorubicin, Asian Pacific Journal of Tropical Biomedicine, 11(4), 174. CrossRef
DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev15iss3pp198-209
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