Synergistic Computational and Cellular Investigation of Berberine's Therapeutic Potential in Triple-Negative Breast Cancer
DOI:
https://doi.org/10.70066/jahm.v13i10.2373Keywords:
Breast cancer, berberine, network pharmacology, molecular docking, apoptosis, ADME analysis, cell viabilityAbstract
Background: Breast cancer is a world wide health issue, characterized by lack of efficient treatment modalities, particularly for aggressive sub types of breast cancer like triple negative breast cancer (TNBC). Berberine is a phytoalkaloid alkaloid molecule that has been shown as a promising oncological agent. In the present work in silico network analysis, molecular docking and in vitro studies are employed to examine promise of berberine as therapeutic agent in breast cancer. Methodology: Differentially expressed genes (DEGs) in breast cancer were identified using GEO datasets Network pharmacology, PPI analysis and pathway enrichment revealed berberine’s impact on key biological process. Molecular docking (AutoDock SwissDock) assessed berberine’s binding to breast cancer targets. ADME analysis evaluated its pharmaco kinetic properties. In vitro studies on breast cancer cell lines examined berberine’s effects on cell viability proliferation and apoptosis using dose-dependent MTT, and ATP based assays highlighting its potential as therapeutic agent. Results: In silico network analysis identified berberine to impact key signalling pathway and interact with significant differentially expressed genes of breast cancer significance. Molecular docking studies demonstrate high affinities of berberine binding to certain target proteins, which were substantiated by good pharmacokinetic potential identified through ADME study. In vitro studies revealed the dose dependent effect of berberine in inhibiting cell viability inducing apoptosis and causing morphological alteration in TNBC cells thereby validating its drug potential. Conclusion: This holistic investigation emphasize the cancer therapeutic efficacy of berberine using network re construction, direct protein interaction with cancer proteins and apoptosis induction in cancer cells. Although these findings emphasize the therapeutic efficacy of berberine experimental validation and clinical trials must be performed prior to the development of targeted and personalized drug which will likely enhance efficacy of breast cancer therapy.
References
Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, Vignat J, Gralow JR, Cardoso F, Siesling S, Soerjomataram I. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast. 2022 Dec;66:15–23. doi: 10.1016/j.breast.2022.08.010.
Xiong X, Zheng LW, Ding Y, Chen YF, Cai YW, Wang LP, Huang L, Liu CC, Shao ZM, Yu KD. Breast cancer: pathogenesis and treatments. Signal Transduct Target Ther. 2025 Feb;10(1):49. doi: 10.1038/s41392-024-02108-4.
Ye F, Dewanjee S, Li Y, Jha NK, Chen ZS, Kumar A, Vishakha, Behl T, Jha SK, Tang H. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer. Mol Cancer. 2023 Jul;22(1):105. doi: 10.1186/s12943-023-01805-y.
Dogra AK, Prakash A, Gupta S, Gupta M. Prognostic Significance and Molecular Classification of Triple Negative Breast Cancer: A Systematic Review. Eur J Breast Health. 2025 Mar;21(2):101–114. doi: 10.4274/ejbh.galenos.2025.2024-10-2.
Karim AM, Kwon JE, Ali T, Jang J, Ullah I, Lee YG, Park DW, Park J, Jeang JW, Kang SC. Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies. Biochem Pharmacol. 2023 Jun;212:115545. doi: 10.1016/j.bcp.2023.115545.
Farina S, Sabatelli A, Boccia S, Scambia G. Environment, lifestyle, and cancer in women. Int J Gynaecol Obstet. 2025 Sep;171 Suppl 1:S138–S146. doi: 10.1002/ijgo.70156.
Prathap L, Suganthirababu P. Estrogen Exposure and its Influence in DNA Repair Genetic Variants in Breast Cancer Population. Biomed Pharmacol J. 2020;13(3).
Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer (Dove Med Press). 2019 Apr;11:151–164. doi: 10.2147/BCTT.S176070.
Liu B, Zhou H, Tan L, et al. Exploring treatment options in cancer: tumor treatment strategies. Signal Transduct Target Ther. 2024;9:175. doi: 10.1038/s41392-024-01856-7.
Yuan M, Zhang G, Bai W, Han X, Li C, Bian S. The Role of Bioactive Compounds in Natural Products Extracted from Plants in Cancer Treatment and Their Mechanisms Related to Anticancer Effects. Oxid Med Cell Longev. 2022 Feb;2022:1429869. doi: 10.1155/2022/1429869.
Xu X, Yi H, Wu J, Kuang T, Zhang J, Li Q, Du H, Xu T, Jiang G, Fan G. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 2021;133:110984. doi: 10.1016/j.biopha.2020.110984.
Neag MA, Mocan A, Echeverría J, Pop RM, Bocsan CI, Crişan G, Buzoianu AD. Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacol. 2018 Aug;9:557. doi: 10.3389/fphar.2018.00557.
Patel P. A bird's eye view on a therapeutically ‘wonder molecule’: Berberine. Phytomed Plus. 2021;1(3):100070. doi: 10.1016/j.phyplu.2021.100070.
Cui D, Zhang C, Zhang L, et al. Natural anti-cancer products: insights from herbal medicine. Chin Med. 2025;20:82. doi: 10.1186/s13020-025-01124-y.
Almatroodi SA, Alsahli MA, Rahmani AH. Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways. Molecules. 2022 Sep;27(18):5889. doi: 10.3390/molecules27185889.
Li Q, Zhao H, Chen W, Huang P. Berberine induces apoptosis and arrests the cell cycle in multiple cancer cell lines. Arch Med Sci. 2021 Mar;19(5):1530–1537. doi: 10.5114/aoms/132969.
Wang R, Wu H, Feng M, Zhong J, Li R, Zhou B. Berberine as a multi-targeted therapeutic agent in melanoma: mechanisms, efficacy, and combination therapies. Drug Dev Res. 2025. doi: 10.1002/ddr.70144.
Zhang L, Wu X, Yang R, Chen F, Liao Y, Zhu Z, Wu Z, Sun X, Wang L. Effects of Berberine on the Gastrointestinal Microbiota. Front Cell Infect Microbiol. 2021 Feb;10:588517. doi: 10.3389/fcimb.2020.588517.
Yang F, Gao R, Luo X, Liu R, Xiong D. Berberine influences multiple diseases by modifying gut microbiota. Front Nutr. 2023 Aug;10:1187718. doi: 10.3389/fnut.2023.1187718.
Sajeev A, Sailo B, Unnikrishnan J, Talukdar A, Alqahtani MS, Abbas M, Alqahtani A, Sethi G, Kunnumakkara AB. Unlocking the potential of Berberine: Advancing cancer therapy through chemosensitization and combination treatments. Cancer Lett. 2024 Aug;597:217019. doi: 10.1016/j.canlet.2024.217019.
El Khalki L, Maire V, Dubois T, Zyad A. Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses. Molecules. 2020 Jan;25(3):506. doi: 10.3390/molecules25030506.
Huang B, Wen G, Li R, Wu M, Zou Z. Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer. Medicine (Baltimore). 2023 Sep;102(36):e35070. doi: 10.1097/MD.0000000000035070.
Ahmadi M, Barkhoda N, Alizamir A, Taherkhani A. Potential Therapeutic Targets in Triple-Negative Breast Cancer Based on Gene Regulatory Network Analysis: A Comprehensive Systems Biology Approach. Int J Breast Cancer. 2024 Oct;2024:8796102. doi: 10.1155/2024/8796102.
Suo HD, Tao Z, Zhang L, Jin ZN, Li XY, Ma W, Wang Z, Qiu Y, Jin F, Chen B, Cao Y. Coexpression Network Analysis of Genes Related to the Characteristics of Tumor Stemness in Triple-Negative Breast Cancer. Biomed Res Int. 2020 Jul;2020:7575862. doi: 10.1155/2020/7575862.
Dayalan H, Bupesh G, Kirubakaran D, Mathe D, Panigrahi J. Chloroquine as a potential anticancer agent for triple-negative breast cancer: effects on MDA-MB-231 cells. Med Oncol. 2025 Jun;42(7):245. doi: 10.1007/s12032-025-02780-8.
Hassan A, Aubel C. The PI3K/Akt/mTOR Signaling Pathway in Triple-Negative Breast Cancer: A Resistance Pathway and a Prime Target for Targeted Therapies. Cancers (Basel). 2025 Jul;17(13):2232. doi: 10.3390/cancers17132232.
Rauf A, Abu-Izneid T, Khalil AA, Imran M, Shah ZA, Emran TB, Mitra S, Khan Z, Alhumaydhi FA, Aljohani ASM, Khan I, Rahman MM, Jeandet P, Gondal TA. Berberine as a Potential Anticancer Agent: A Comprehensive Review. Molecules. 2021 Dec;26(23):7368. doi: 10.3390/molecules26237368.
Zhao L, Zhang C. Berberine Inhibits MDA-MB-231 Cells by Attenuating Their Inflammatory Responses. Biomed Res Int. 2020 Mar;2020:3617514. doi: 10.1155/2020/3617514.
Barzegar E, Fouladdel S, Movahhed TK, Atashpour S, Ghahremani MH, Ostad SN, Azizi E. Effects of berberine on proliferation, cell cycle distribution and apoptosis of human breast cancer T47D and MCF7 cell lines. Iran J Basic Med Sci. 2015 Apr;18(4):334–342.
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Vummini Krishnamurthy Sri Keerti, Monisha Prasad, Shenbhagaraman Ramalingam
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors retain the copyright of their work and grant the Journal of Ayurveda and Holistic Medicine (JAHM) the right of first publication. All published articles are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) license, which permits non-commercial sharing, use, distribution, and adaptation with proper attribution and the same license terms.
JAHM ensures free, irrevocable, worldwide access to its content. Users may copy, distribute, display, and share published works for non-commercial purposes with appropriate credit to the author(s) and the journal. Limited printed copies for personal, non-commercial use are allowed under the same license.
If a submission is not accepted for publication, the author(s) will be notified.
By submitting, authors confirm that the work is original, that all listed authors have contributed and approved it, and that it does not infringe any third-party rights or duplicate work submitted elsewhere.
