Regulation of IL-10 by Herbal and Hormonal Therapy: The Impact of Eleutherine Bulbosa and Tamoxifen in an Experimental Breast Cancer Model Effects of Eleutherine bulbosa–Tamoxifen on interleukin-10
Abstract
Background: Breast cancer is the most common cancer affecting women worldwide, with the number of cases and deaths continuing to rise. This study evaluated the single and combined effects of Eleutherine bulbosa ethanol extract and tamoxifen in reducing interleukin-10 (IL-10) levels in BALB/c mice with breast cancer models.
Methods: This study used a laboratory experimental approach with a post-test-only control group design, using 36 female Mus musculus BALB/c strain mice (aged 8-10 weeks), randomly divided into six groups: negative and positive control groups. The intervention groups were given Eleutherine bulbosa ethanol extract at a dose of 180 mg/kg BW for 14 days, tamoxifen at a dose of 10 mg/kg BW every 2 days for 7 days within a 14-day period, a combination of Eleutherine bulbosa ethanol extract and tamoxifen, and tamoxifen and Eleutherine bulbosa ethanol extract. Effectiveness was evaluated based on IL-10 levels in serum.
Results: This study found that the combination of tamoxifen and ethanol extract from Eleutherine bulbosa significantly reduced IL-10 levels in BALB/c mice with a breast cancer model. The extract Eleutherine bulbosa ethanol extract reduced IL-10 by 31.4%, while tamoxifen reduced it by 59.1%. The strongest synergistic effect was observed when combined with tamoxifen, reducing IL-10 levels by 64.6%, indicating its effectiveness in suppressing the immunosuppressive response supporting tumor growth.
Conclusion: Tamoxifen and Eleutherine bulbosa extract showed synergistic effects in reducing IL-10 levels, suggesting enhanced immunomodulatory action compared to monotherapy. This combination can enhance breast cancer treatment efficacy by diminishing immunosuppression.
Full text article
References
Bakhsh T, Alyami NM. Inducing breast cancer cell death: The impact of taxodone on proliferation through apoptosis. Heliyon. 2024;10(13):e34044. doi:10.1016/j.heliyon.2024.e34044. DOI: https://doi.org/10.1016/j.heliyon.2024.e34044
Breast. American Cancer Society. Available from: https://cancerstatisticscenter.cancer.org/types/breast
Katalog Data- Layanan Permintaan Data | Kementerian Kesehatan RI. Available from: https://layanandata.kemkes.go.id/katalog- data/ski/ketersediaan-data/ski-2023
Vilchis-Landeros MM, Vázquez-Meza H, Vázquez- Carrada M, Uribe-Ramírez D, Matuz-Mares D. Antioxidant Enzymes and Their Potential Use in Breast Cancer Treatment. Int J Mol Sci. 2024 23;25(11):5675. doi:10.3390/ijms25115675. DOI: https://doi.org/10.3390/ijms25115675
Dubey A, Sharma B. Targeting Oxidative Stress Biomarkers in Breast Cancer Development and the Potential Protective Effect of Phytochemicals. Drugs Drug Candidates. 2025 23;4(2):23. doi:10.3390/ddc4020023. DOI: https://doi.org/10.3390/ddc4020023
Carlini V, Noonan DM, Abdalalem E, Goletti D, Sansone C, Calabrone L, et al. The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions. Front Immunol. 2023 8;14:1161067. doi:10.3389/fimmu.2023.1161067. DOI: https://doi.org/10.3389/fimmu.2023.1161067
Islam H, Chamberlain TC, Mui AL, Little JP. Elevated Interleukin-10 Levels in COVID-19: Potentiation of Pro-Inflammatory Responses or Impaired Anti-Inflammatory Action? Front Immunol. 2021 21;12:677008. doi:10.3389/fimmu.2021.677008. DOI: https://doi.org/10.3389/fimmu.2021.677008
Sun H, Wu Y, Zhang Y, Ni B. IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance. Front Immunol. 2021 29;12. doi:10.3389/fimmu.2021.650200. DOI: https://doi.org/10.3389/fimmu.2021.650200
Heimes AS, Shehaj I, Almstedt K, Krajnak S, Schwab R, Stewen K, et al. Prognostic Impact of Acute and Chronic Inflammatory Interleukin Signatures in the Tumor Microenvironment of Early Breast Cancer. Int J Mol Sci. 2024 16;25(20):11114. doi:10.3390/ijms252011114. DOI: https://doi.org/10.3390/ijms252011114
Raheem F, Karikalan SA, Batalini F, El Masry A, Mina L. Metastatic ER+ Breast Cancer: Mechanisms of Resistance and Future Therapeutic Approaches. Int J Mol Sci. 2023; 11;24(22):16198. doi:10.3390/ijms242216198. DOI: https://doi.org/10.3390/ijms242216198
Zhuo Z, Zhang D, Lu W, Wu X, Cui Y, Zhang W, et al. Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation. Oncol Res. 2024;32(6):1093–107. doi:10.32604/or.2024.047257. DOI: https://doi.org/10.32604/or.2024.047257
Zhang J, Liu J, Yue Y, Wang L, He Q, Xu S, et al. The immunotoxin targeting PRLR increases tamoxifen sensitivity and enhances the efficacy of chemotherapy in breast cancer. J Exp Clin Cancer Res. 2024 20;43(1):173. doi:10.1186/s13046-024-03099-4. DOI: https://doi.org/10.1186/s13046-024-03099-4
Nurkolis F, Kurniatanty I, Wiyarta E, Permatasari HK, Mayulu N, Taslim NA, et al. Identification of novel functional compounds from forest onion and its biological activities against breast cancer. J Agric Food Res. 2024;18(101362). doi:10.1016/j.jafr.2024.101362. DOI: https://doi.org/10.1016/j.jafr.2024.101362
Silva RMG da, Alves CP, Barbosa FC, Santos HH, Adão KM, Granero FO, et al. Antioxidant, antitumoral, antimetastatic effect and inhibition of collagenase enzyme activity of Eleutherine bulbosa (Dayak onion) extract: In vitro, in vivo and in silico approaches. J Ethnopharmacol. 2024;10;318(Pt B):117005. doi:10.1016/j.jep.2023.117005. DOI: https://doi.org/10.1016/j.jep.2023.117005
Arbain D, Sriwahyuni K, Susanti D, Taher M. Genus Eleutherine: A review of its distribution, traditional uses, phytochemistry, biological activities and its interchangeable common names. South Afr J Bot. 2022;150:731–43. doi:10.1016/j.sajb.2022.08.022. DOI: https://doi.org/10.1016/j.sajb.2022.08.022
Kamarudin AA, Sayuti NH, Saad N, Razak NAA, Esa NM. Eleutherine bulbosa (Mill.) Urb. Bulb: Review of the Pharmacological Activities and Its Prospects for Application. Int J Mol Sci. 2021;23;22(13):6747. doi:10.3390/ijms22136747. DOI: https://doi.org/10.3390/ijms22136747
Laskar YB, Bhattacharjee K, Nath M, Choudhury Y, Mazumder PB, Talukdar AD. Protective Effects of Pelargonidin against DMBA-Induced Mammary Tumorigenesis in BALB/c Mice through Reduced Oxidative Stress and Lipid Anomalies. Nutr Cancer. 2023;9;75(7):1579–99. doi:10.1080/01635581.2023.2219027. DOI: https://doi.org/10.1080/01635581.2023.2219027
Efrem DG, Ilmiawan MI, Pratiwi SE. Chemopreventive effect of dayak onion [Eleutherine bulbosa, Mill. (Urb)] against 7,12-dimethylbenz [α] anthracene (DMBA)-induced breast cancer in rats: study on cancer antigen 15-3 (CA 15-3). Indones J Biomed Clin Sci. 2024;21 ;56(3). doi:10.22146/inajbcs.v56i3.12245. DOI: https://doi.org/10.22146/inajbcs.v56i3.12245
Moghadam RH, Rouzbahani M, Salehi N, Sadeghi M. Association between blood Interleukin-10 level in coronary artery disease: A systematic review, meta-analysis, and network analyses. Biomed Res Ther. 2024;31;11(7):6603–21. doi:10.15419/bmrat.v11i7.907. DOI: https://doi.org/10.15419/bmrat.v11i7.907
Matariek G, Teibo JO, Elsamman K, Teibo TKA, Olatunji DI, Matareek A, et al. Tamoxifen: The Past, Present, and Future of a Previous Orphan Drug. Eur J Med Health Sci. 2022;24;4(3):1–10. doi:10.24018/ejmed.2022.4.3.1124. DOI: https://doi.org/10.24018/ejmed.2022.4.3.1124
Zhang L, Virgous C, Si H. Synergistic anti- inflammatory effects and mechanisms of combined phytochemicals. J Nutr Biochem. 2019;69:19–30. doi:10.1016/j.jnutbio.2019.03.009. DOI: https://doi.org/10.1016/j.jnutbio.2019.03.009
Huang H, Zhou J, Chen H, Li J, Zhang C, Jiang X, et al. The immunomodulatory effects of endocrine therapy in breast cancer. J Exp Clin Cancer Res. 2021;7;40(1):19. doi:10.1186/s13046-020-01788-4. DOI: https://doi.org/10.1186/s13046-020-01788-4
Sfogliarini C, Pepe G, Dolce A, Della Torre S, Cesta MC, Allegretti M, et al. Tamoxifen Twists Again: On and Off-Targets in Macrophages and Infections. Front Pharmacol. 2022;30;13:879020. doi:10.3389/fphar.2022.879020. DOI: https://doi.org/10.3389/fphar.2022.879020
Kubatka P, Koklesova L, Mazurakova A, Brockmueller A, Büsselberg D, Kello M, et al. Cell plasticity modulation by flavonoids in resistant breast carcinoma targeting the nuclear factor kappa B signaling. Cancer Metastasis Rev. 2024;43(1):87–113. doi:10.1007/s10555-023-10134-x. DOI: https://doi.org/10.1007/s10555-023-10134-x
Wang S, Wang J, Chen Z, Luo J, Guo W, Sun L, et al. Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance. Npj Precis Oncol. 2024;10;8(1):31. doi:10.1038/s41698-024-00522-z. DOI: https://doi.org/10.1038/s41698-024-00522-z
Yen C, Zhao F, Yu Z, Zhu X, Li CG. Interactions Between Natural Products and Tamoxifen in Breast Cancer: A Comprehensive Literature Review. Front Pharmacol. 2022;2;13:847113. doi:10.3389/fphar.2022.847113. DOI: https://doi.org/10.3389/fphar.2022.847113
Sun Z, Li Q, Zhang J, Sun Z, Wu H, Liang H, et al. Phenolic constituents with antibacterial activity from Eleutherine bulbosa. Fitoterapia. 2024;1;172:105787. doi:10.1016/j.fitote.2023.105787. DOI: https://doi.org/10.1016/j.fitote.2023.105787
Zakaria NH, Saad N, Che Abdullah CA, Mohd. Esa N. The Antiproliferative Effect of Chloroform Fraction of Eleutherine bulbosa (Mill.) Urb. on 2D- and 3D-Human Lung Cancer Cells (A549) Model. Pharmaceuticals. 2023;28;16(7):936. doi:10.3390/ph16070936. DOI: https://doi.org/10.3390/ph16070936
Mulder TAM, de With M, del Re M, Danesi R, Mathijssen RHJ, van Schaik RHN. Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy. Cancers. 2021;13(4):771. doi:10.3390/cancers13040771. DOI: https://doi.org/10.3390/cancers13040771
Authors
Copyright (c) 2026 Archives of Breast Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.