Icariin as a therapeutic agent in breast cancer: modulating apoptosis and suppressing proliferation
-
Kavita Goyal
,
Poonam Negi
Abstract
Breast cancer remains the leading cause of cancer-related death worldwide, underscoring the urgent need for novel therapeutic strategies. Icariin, a prenylated flavonol glycoside derived from Epimedium species, has emerged as a promising multi-targeted agent with potent anticancer activity. Preclinical studies demonstrate that icariin modulates key oncogenic pathways, including PI3K/Akt, MAPK, NF-κB/SIRT6, and AMPK/mTOR to inhibit tumor cell proliferation, induce apoptosis, and regulate autophagy. Moreover, icariin exhibits anti-metastatic effects by suppressing epithelial-to-mesenchymal transition, matrix metalloproteinase activity, and immunomodulatory actions that may enhance antitumor immunity. Despite these encouraging findings, a comprehensive understanding of its molecular mechanisms and translational potential remains limited. Here, we systematically review the latest in vitro and in vivo evidence on icariin’s pharmacological effects in breast cancer models. We highlight advances in nanoformulation approaches to improve their bioavailability and identify critical knowledge gaps. This review aims to guide future research toward optimized delivery systems and well-designed clinical trials by integrating mechanistic insights with formulation science. Ultimately, elucidating the full therapeutic profile of icariin will inform its incorporation into complementary and integrative oncology regimens, potentially improving outcomes for patients with diverse breast cancer subtypes.
-
Research ethics: Not applicable.
-
Informed consent: Not applicable.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: Not applicable.
References
1. Arnold, M, Morgan, E, Rumgay, H, Mafra, A, Singh, D, Laversanne, M, et al.. Current and future burden of breast cancer: global statistics for 2020 and 2040. Breast 2022;66:15–23. https://doi.org/10.1016/j.breast.2022.08.010.Search in Google Scholar PubMed PubMed Central
2. Bhat, AA, Afzal, M, Moglad, E, Thapa, R, Ali, H, Almalki, WH, et al.. lncRNAs as prognostic markers and therapeutic targets in cuproptosis-mediated cancer. Clin Exp Med 2024;24:226. https://doi.org/10.1007/s10238-024-01491-0.Search in Google Scholar PubMed PubMed Central
3. Bhat, AA, Moglad, E, Afzal, M, Agrawal, N, Thapa, R, Almalki, WH, et al.. The anticancer journey of liquiritin: insights into its mechanisms and therapeutic prospects. Curr Med Chem 2024. https://doi.org/10.2174/0109298673315699240805111122.Search in Google Scholar PubMed
4. Zafar, A, Khatoon, S, Khan, MJ, Abu, J, Naeem, A. Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy. Discov Oncol 2025;16:607. https://doi.org/10.1007/s12672-025-02198-8.Search in Google Scholar PubMed PubMed Central
5. Sharma, V, Pandey, S, Gupta, G, Gandhi, A, Rastogi, M, Sethi, R, et al.. A novel oncoplastic technique for centrally located breast cancers: an experience from a Tertiary care center in North India. Indian J Cancer 2024;61:687–93. https://doi.org/10.4103/ijc.2024.1063.20.Search in Google Scholar
6. Liu, FY, Ding, DN, Wang, YR, Liu, SX, Peng, C, Shen, F, et al.. Icariin as a potential anticancer agent: a review of its biological effects on various cancers. Front Pharmacol 2023;14:1216363. https://doi.org/10.3389/fphar.2023.1216363.Search in Google Scholar PubMed PubMed Central
7. Shi, W, Gao, Y, Wang, Y, Zhou, J, Wei, Z, Ma, X, et al.. The flavonol glycoside icariin promotes bone formation in growing rats by activating the cAMP signaling pathway in primary cilia of osteoblasts. J Biol Chem 2017;292:20883–96. https://doi.org/10.1074/jbc.m117.809517.Search in Google Scholar
8. Singh, S, Saxena, S, Sharma, H, Paudel, KR, Chakraborty, A, MacLoughlin, R, et al.. Emerging role of tumor suppressing microRNAs as therapeutics in managing non-small cell lung cancer. Pathol Res Pract 2024;256:155222. https://doi.org/10.1016/j.prp.2024.155222.Search in Google Scholar PubMed
9. Xu, C, Huang, X, Tong, Y, Feng, X, Wang, Y, Wang, C, et al.. Icariin modulates the sirtuin/NF-κB pathway and exerts anti-aging effects in human lung fibroblasts. Mol Med Rep 2020;22:3833–9. https://doi.org/10.3892/mmr.2020.11458.Search in Google Scholar PubMed PubMed Central
10. Yersal, O, Barutca, S. Biological subtypes of breast cancer: prognostic and therapeutic implications. World J Clin Oncol 2014;5:412–24. https://doi.org/10.5306/wjco.v5.i3.412.Search in Google Scholar PubMed PubMed Central
11. Thangavelu, L, Moglad, E, Gupta, G, Menon, SV, Gaur, A, Sharma, S, et al.. GAS5 lncRNA: a biomarker and therapeutic target in breast cancer. Pathol Res Pract 2024;260:155424. https://doi.org/10.1016/j.prp.2024.155424.Search in Google Scholar PubMed
12. Cheng, X, Tan, S, Duan, F, Yuan, Q, Li, Q, Deng, G. Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM. Breast Cancer 2019;26:766–75. https://doi.org/10.1007/s12282-019-00980-5.Search in Google Scholar PubMed PubMed Central
13. Uppu, JL, Challa, VS, Syamprasad, NP, Manepalli, P, Naidu, V, Syed, A, et al.. Apoptosis-driven synergistic anti-cancer efficacy of ethyl acetate extract of Memecylon sisparense Gamble leaves and doxorubicin in in-vitro and in-vivo models of triple-negative breast cancer. Pathol Res Pract 2024;253:155032. https://doi.org/10.1016/j.prp.2023.155032.Search in Google Scholar PubMed
14. Zhao, M, Xu, P, Shi, W, Wang, J, Wang, T, Li, P. Icariin exerts anti-tumor activity by inducing autophagy via AMPK/mTOR/ULK1 pathway in triple-negative breast cancer. Cancer Cell Int 2024;24:74. https://doi.org/10.1186/s12935-024-03266-9.Search in Google Scholar PubMed PubMed Central
15. Gupta, G, Hussain, MS, Pant, K, Ali, H, Thapa, R, Bhat, AA. Antibody-drug conjugates (ADCs): a novel therapy for triple-negative breast cancer (TNBC). Curr Cancer Drug Targets 2025;25:108–12. https://doi.org/10.2174/0115680096343056240828190900.Search in Google Scholar PubMed
16. Żabińska, M, Wiśniewska, K, Węgrzyn, G, Pierzynowska, K. Exploring the physiological role of the G protein-coupled estrogen receptor (GPER) and its associations with human diseases. Psychoneuroendocrinology 2024;166:107070. https://doi.org/10.1016/j.psyneuen.2024.107070.Search in Google Scholar PubMed
17. Hussain, MS, Mujwar, S, Babu, MA, Goyal, K, Chellappan, DK, Negi, P, et al.. Pharmacological, computational, and mechanistic insights into triptolide’s role in targeting drug-resistant cancers. Naunyn-Schmiedebergs Arch Pharmacol 2025;398:6509–30. https://doi.org/10.1007/s00210-025-03809-5.Search in Google Scholar PubMed
18. Xie, L, Deng, Z, Zhang, J, Dong, H, Wang, W, Xing, B, et al.. Comparison of flavonoid O-glycoside, C-glycoside and their aglycones on antioxidant capacity and metabolism during in vitro digestion and in vivo. Foods 2022;11:882. https://doi.org/10.3390/foods11060882.Search in Google Scholar PubMed PubMed Central
19. Lu, Y, Luo, Q, Jia, X, Tam, JP, Yang, H, Shen, Y, et al.. Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: integration of herbal medicine, enzyme engineering, and nanotechnology. J Pharm Anal 2023;13:239–54. https://doi.org/10.1016/j.jpha.2022.12.001.Search in Google Scholar PubMed PubMed Central
20. Lalhminghlui, K, Jagetia, GC. Evaluation of the free-radical scavenging and antioxidant activities of Chilauni, Schima wallichii Korth in vitro. Future Science OA 2018;4:Fso272. https://doi.org/10.4155/fsoa-2017-0086.Search in Google Scholar PubMed PubMed Central
21. Zhuang, W, Sun, N, Gu, C, Liu, S, Zheng, Y, Wang, H, et al.. A literature review on Epimedium, a medicinal plant with promising slow aging properties. Heliyon 2023;9:e21226. https://doi.org/10.1016/j.heliyon.2023.e21226.Search in Google Scholar PubMed PubMed Central
22. Deng, L, Ouyang, B, Shi, H, Yang, F, Li, S, Xie, C, et al.. Icariside II attenuates bleomycin-induced pulmonary fibrosis by modulating macrophage polarization. J Ethnopharmacol 2023;317:116810. https://doi.org/10.1016/j.jep.2023.116810.Search in Google Scholar PubMed
23. Deng, CJ, Li, X, Zeng, Y, Jiang, J, Jiang, R. Icariin inhibits the formation of mitochondria-associated membranes (MAMs) and improves erectile function in rats treated with prostate radiation. Andrology 2022;10:1208–16. https://doi.org/10.1111/andr.13218.Search in Google Scholar PubMed
24. Dong, Y, Wang, L, Yang, M, Zhou, X, Li, G, Xu, K, et al.. Effect of icariin on depressive behaviour in rat pups. Evidences for its mechanism of action by integrating network pharmacology, metabolomics and gut microbiota composition. Phytomedicine 2024;126:155422. https://doi.org/10.1016/j.phymed.2024.155422.Search in Google Scholar PubMed
25. Dong, J, Chen, S, Ma, K, Zhao, L, Huang, D, Li, Z, et al.. Icariin improves the viability and function of cryopreserved human nucleus pulposus-derived mesenchymal stem cells. BMC Compl Alternative Med 2018;2018:3459612. https://doi.org/10.1155/2018/3459612.Search in Google Scholar PubMed PubMed Central
26. Jia, J, Zhao, XA, Tao, SM, Wang, JW, Zhang, RL, Dai, HL, et al.. Icariin improves cardiac function and remodeling via the TGF-β1/Smad signaling pathway in rats following myocardial infarction. Eur J Med Res 2023;28:607. https://doi.org/10.1186/s40001-023-01588-4.Search in Google Scholar PubMed PubMed Central
27. 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. 2024;43:87–113. https://doi.org/10.1007/s10555-023-10134-x.Search in Google Scholar PubMed PubMed Central
28. Gao, S, Zhang, X, Liu, J, Ji, F, Zhang, Z, Meng, Q, et al.. Icariin induces triple-negative breast cancer cell apoptosis and suppresses invasion by inhibiting the JNK/c-Jun signaling pathway. Cancer Sci 2023;17:821–36. https://doi.org/10.2147/dddt.s398887.Search in Google Scholar
29. Hong, J, Zhang, Z, Lv, W, Zhang, M, Chen, C, Yang, S, et al.. Icaritin synergistically enhances the radiosensitivity of 4T1 breast cancer cells. PLoS One 2013;8:e71347. https://doi.org/10.1371/journal.pone.0071347.Search in Google Scholar PubMed PubMed Central
30. Elmore, S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35:495–516. https://doi.org/10.1080/01926230701320337.Search in Google Scholar PubMed PubMed Central
31. Fang, L, Xu, W, Kong, D. Retraction notice to “Icariin inhibits cell proliferation, migration and invasion by down-regulation of microRNA-625-3p in thyroid cancer cells” [Biomed. Pharmacother. 109 (2019) 2456–2463]. Biomed Pharmacother 2022;150:112851. https://doi.org/10.1016/j.biopha.2022.112851.Search in Google Scholar PubMed
32. Fang, L, Xu, W, Kong, D. RETRACTED: icariin inhibits cell proliferation, migration and invasion by down-regulation of microRNA-625-3p in thyroid cancer cells. Biomed Pharmacother 2019;109:2456–63. https://doi.org/10.1016/j.biopha.2018.04.012.Search in Google Scholar PubMed
33. Song, L, Chen, X, Mi, L, Liu, C, Zhu, S, Yang, T, et al.. Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative. Breast Cancer 2020;111:4242–56. https://doi.org/10.1111/cas.14648.Search in Google Scholar PubMed PubMed Central
34. Biegler, KA, Chaoul, MA, Cohen, L. Cancer, cognitive impairment, and meditation. J Cell Mol Med 2009;48:18–26. https://doi.org/10.1080/02841860802415535.Search in Google Scholar PubMed
35. Krstic, J, Pieber, TR, Prokesch, A. Stratifying nutritional restriction in cancer therapy: next stop, personalized medicine. Int Rev Cell Mol Biol 2020;354:231–59. https://doi.org/10.1016/bs.ircmb.2020.03.001.Search in Google Scholar PubMed
36. Goldberg, K, Bar-Joseph, H, Grossman, H, Hasky, N, Uri-Belapolsky, S, Stemmer, SM, et al.. Pigment epithelium-derived factor alleviates tamoxifen-induced endometrial hyperplasia. Mol Cancer Therapeut 2015;14:2840–9. https://doi.org/10.1158/1535-7163.mct-15-0523.Search in Google Scholar
37. Farzaei, MH, Bahramsoltani, R, Rahimi, R. Phytochemicals as adjunctive with conventional anticancer therapies. Curr Pharm Des 2016;22:4201–18. https://doi.org/10.2174/1381612822666160601100823.Search in Google Scholar PubMed
38. Campbell-Fleming, JM, Williams, A. The use of ketamine as adjuvant therapy to control severe pain. Clin J Oncol Nurs 2008;12:102–7. https://doi.org/10.1188/08.cjon.102-107.Search in Google Scholar
39. Chen, Y, Pan, X, Zhao, J, Li, C, Lin, Y, Wang, Y, et al.. Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway. Eur J Med Res 2022;27:204. https://doi.org/10.1186/s40001-022-00820-x.Search in Google Scholar PubMed PubMed Central
40. Wu, Q, Sharma, D. Autophagy and breast cancer: connected in growth, progression, and therapy. Cells 2023;12:1156. https://doi.org/10.3390/cells12081156.Search in Google Scholar PubMed PubMed Central
41. Ji, R, Wu, D, Liu, Q. Icariin inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells via inhibition of reactive oxygen species production by reducing the expression of NOX1 and NOX4. Biochem Biophys Res Commun 2022;600:6–13. https://doi.org/10.1016/j.bbrc.2022.02.023.Search in Google Scholar PubMed
42. Zhou, J, Wu, J, Chen, X, Fortenbery, N, Eksioglu, E, Kodumudi, KN, et al.. Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions. Int Immunopharmacol 2011;11:890–8. https://doi.org/10.1016/j.intimp.2011.01.007.Search in Google Scholar PubMed PubMed Central
43. Yong, EL, Cheong, WF, Huang, Z, Thu, WPP, Cazenave-Gassiot, A, Seng, KY, et al.. Randomized, double-blind, placebo-controlled trial to examine the safety, pharmacokinetics and effects of Epimedium prenylflavonoids, on bone specific alkaline phosphatase and the osteoclast adaptor protein TRAF6 in post-menopausal women. Phytomedicine 2021;91:153680. https://doi.org/10.1016/j.phymed.2021.153680.Search in Google Scholar PubMed
44. Chen, X, Zhu, P, Liu, B, Wei, L, Xu, Y. Simultaneous determination of fourteen compounds of Hedyotis diffusa Willd extract in rats by UHPLC-MS/MS method: application to pharmacokinetics and tissue distribution study. J Pharmaceut Biomed Anal 2018;159:490–512. https://doi.org/10.1016/j.jpba.2018.07.023.Search in Google Scholar PubMed
45. Liu, T, Zhao, M, Zhang, Y, Qiu, Z, Zhang, Y, Zhao, C, et al.. Pharmacokinetic-pharmacodynamic modeling analysis and anti-inflammatory effect of Wangbi capsule in the treatment of adjuvant-induced arthritis. Biomed Chromatogr 2021;35:e5101. https://doi.org/10.1002/bmc.5101.Search in Google Scholar PubMed
46. Li, S, Liu, H, Zhang, C, An, D, Zhao, X, Liu, W, et al.. Serum pharmacochemistry and pharmacokinetics of major components after oral administration of Luhong recipe in rats using ultra-performance liquid chromatography-tandem mass spectrometry. Molecules 2022;36:e5497. https://doi.org/10.1002/bmc.5497.Search in Google Scholar PubMed
47. Reyes-Hernández, OD, Figueroa-González, G, Quintas-Granados, LI. New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives. Drug Dev Res 2024;85:e2217510.1002/ddr.22175Search in Google Scholar PubMed
48. Dai, W, Jin, P, Li, X, Zhao, J, Lan, Y, Li, H, et al.. A carrier-free nano-drug assembled via π-π stacking interaction for the treatment of osteoarthritis. Biomed Pharmacother 2023;164:114881. https://doi.org/10.1016/j.biopha.2023.114881.Search in Google Scholar PubMed
49. Fan, J, Bi, L, Wu, T, Cao, L, Wang, D, Nan, K, et al.. A combined chitosan/nano-size hydroxyapatite system for the controlled release of icariin. J Mater Sci Mater Med 2012;23:399–407. https://doi.org/10.1007/s10856-011-4491-4.Search in Google Scholar PubMed
50. Gao, L, Zhang, SQ. Antiosteoporosis effects, pharmacokinetics, and drug delivery systems of icaritin: advances and prospects. Pharmaceuticals (Basel) 2022;15:397.10.3390/ph15040397Search in Google Scholar PubMed PubMed Central
51. Huang, JG, Pang, L, Chen, ZR, Tan, XP. Dual-delivery of vancomycin and icariin from an injectable calcium phosphate cement-release system for controlling infection and improving bone healing. Mol Med Rep 2013;8:1221–7. https://doi.org/10.3892/mmr.2013.1624.Search in Google Scholar PubMed
52. Ji, Y, Zhang, Z, Hou, W, Wu, M, Wu, H, Hu, N, et al.. Enhanced antitumor effect of icariin nanoparticles coated with iRGD functionalized erythrocyte membrane. Eur J Pharmacol 2022;931:175225. https://doi.org/10.1016/j.ejphar.2022.175225.Search in Google Scholar PubMed
53. Desantis, V, Lamanuzzi, A, Vacca, A. The role of SIRT6 in tumors. Haematologica 2018;103:1–4. https://doi.org/10.3324/haematol.2017.182675.Search in Google Scholar PubMed PubMed Central
54. Song, L, Chen, X, Mi, L, Liu, C, Zhu, S, Yang, T, et al.. Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer. Cancer Sci 2020;111:4242–56. https://doi.org/10.1111/cas.14648.Search in Google Scholar PubMed PubMed Central
55. Chao, YL, Shepard, CR, Wells, A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer 2010;9:179. https://doi.org/10.1186/1476-4598-9-179.Search in Google Scholar PubMed PubMed Central
56. Gao, S, Zhang, X, Liu, J, Ji, F, Zhang, Z, Meng, Q, et al.. Icariin induces triple-negative breast cancer cell apoptosis and suppresses invasion by inhibiting the JNK/c-Jun signaling pathway. Drug Des Dev Ther 2023;17:821–36. https://doi.org/10.2147/dddt.s398887.Search in Google Scholar PubMed PubMed Central
57. Jung, YY, Lee, JH, Nam, D, Narula, AS, Namjoshi, OA, Blough, BE, et al.. Anti-myeloma effects of icariin are mediated through the attenuation of JAK/STAT3-dependent signaling cascade. Front Pharmacol 2018;9:531. https://doi.org/10.3389/fphar.2018.00531.Search in Google Scholar PubMed PubMed Central
58. Clarke, R, Jones, BC, Sevigny, CM, Hilakivi-Clarke, LA, Sengupta, S. Experimental models of endocrine responsive breast cancer: strengths, limitations, and use. Cancer Drug Resist 2021;4:762–83. https://doi.org/10.20517/cdr.2021.33.Search in Google Scholar PubMed PubMed Central
59. Tran, AT, Ramalinga, M, Kedir, H, Clarke, R, Kumar, D. Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells. Eur J Nutr 2015;54:265–72. https://doi.org/10.1007/s00394-014-0707-y.Search in Google Scholar PubMed PubMed Central
60. Rabanal-Ruiz, Y, Otten, EG, Korolchuk, VI. mTORC1 as the main gateway to autophagy. Essays Biochem 2017;61:565–84. https://doi.org/10.1042/ebc20170027.Search in Google Scholar PubMed PubMed Central
61. Wang, Q, Xiong, F, Wu, G, Wang, D, Liu, W, Chen, J, et al.. SMAD proteins in TGF-β signalling pathway in cancer: regulatory mechanisms and clinical applications. Diagnostics (Basel) 2023;13:2769. https://doi.org/10.3390/diagnostics13172769.Search in Google Scholar PubMed PubMed Central
62. Li, X, Shi, G. Therapeutic effects and mechanism of ferulic acid and icariin in mammary gland hyperplasia model rats via regulation of the ERK pathway. Ann Transl Med 2021;9:666. https://doi.org/10.21037/atm-21-656.Search in Google Scholar PubMed PubMed Central
63. Sharifi-Rad, J, Quispe, C, Imran, M, Rauf, A, Nadeem, M, Gondal, TA, et al.. Genistein: an integrative overview of its mode of action, pharmacological properties, and health benefits. Oxid Med Cell Longev 2021;2021:3268136. https://doi.org/10.1155/2021/3268136.Search in Google Scholar PubMed PubMed Central
64. Zhou, L, Poon, CC, Wong, KY, Cao, S, Dong, X, Zhang, Y, et al.. Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ERα signaling. Phytomedicine 2021;82:153413. https://doi.org/10.1016/j.phymed.2020.153413.Search in Google Scholar PubMed
65. Liu, M, Wang, B, Guo, C, Hou, X, Cheng, Z, Chen, D. Novel multifunctional triple folic acid, biotin and CD44 targeting pH-sensitive nano-actiniaes for breast cancer combinational therapy. Drug Deliv 2019;26:1002–16. https://doi.org/10.1080/10717544.2019.1669734.Search in Google Scholar PubMed PubMed Central
66. Kim, B, Lee, KY, Park, B. Icariin abrogates osteoclast formation through the regulation of the RANKL-mediated TRAF6/NF-κB/ERK signaling pathway in Raw264.7 cells. Phytomedicine 2018;51:181–90. https://doi.org/10.1016/j.phymed.2018.06.020.Search in Google Scholar PubMed
67. Song, B, Wei, F, Peng, J, Wei, X, Liu, M, Nie, Z, et al.. Icariin regulates EMT and stem cell-like character in breast cancer through modulating lncRNA NEAT1/TGFβ/SMAD2 signaling pathway. Biol Pharm Bull 2024;47:399–410. https://doi.org/10.1248/bpb.b23-00668.Search in Google Scholar PubMed
68. Shi, WG, Ma, XN, Xie, YF, Zhou, J, Zhou, J. [Icariin promote maturation of osteoblasts in vitro by an estrogen-independent mechanism]. Zhongguo Zhong Yao Za Zhi 2014;39:2704–9.Search in Google Scholar
69. Liu, M, Wang, B, Guo, C, Hou, X, Cheng, Z, Chen, D. Novel multifunctional triple folic acid, biotin and CD44 targeting pH-sensitive nano-actiniaes for breast cancer combinational therapy. Drug Deliv 2019;26:1002–16. https://doi.org/10.1080/10717544.2019.1669734.Search in Google Scholar
70. Fiorilla, S, Tasso, F, Clemente, N, Trisciuoglio, T, Boldorini, R, Carini, R. Monensin inhibits triple-negative breast cancer in mice by a Na+-dependent cytotoxic action unrelated to cytostatic effects. Cells 2025;14:185. https://doi.org/10.3390/cells14030185.Search in Google Scholar PubMed PubMed Central
71. Zhang, Q, Li, H, Wang, S, Liu, M, Feng, Y, Wang, X. Icariin protects rat cardiac H9c2 cells from apoptosis by inhibiting endoplasmic reticulum stress. Int J Mol Sci 2013;14:17845–60. https://doi.org/10.3390/ijms140917845.Search in Google Scholar PubMed PubMed Central
72. Szabó, R, Rácz, CP, Dulf, FV. Bioavailability improvement strategies for icariin and its derivates: a review. Int J Mol Sci 2022;23:7519. https://doi.org/10.3390/ijms23147519.Search in Google Scholar PubMed PubMed Central
73. Sawant, RR, Torchilin, VP. Polymeric micelles: polyethylene glycol-phosphatidylethanolamine (PEG-PE)-based micelles as an example. Methods Mol Biol 2010;624:131–49. https://doi.org/10.1007/mmb-1-60761-609-29.Search in Google Scholar
74. Wang, J, Sun, Y, Tian, X. The inhibitory effect of icariin nanoparticles on angiogenesis in pulmonary fibrosis. J Nanosci Nanotechnol 2021;21:5429–35. https://doi.org/10.1166/jnn.2021.19316.Search in Google Scholar PubMed
© 2025 Walter de Gruyter GmbH, Berlin/Boston
