Force J, Leal JHS, Mcarthur HL. Checkpoint blockade strategies in the treatment of breast cancer: where we are and where we are heading. Curr Treat Options Oncol. 2019;20:35. https://doi.org/10.1007/s11864-019-0634-5.

Article  PubMed  Google Scholar 

Thorat MA, Balasubramanian R. Breast cancer prevention in high-risk women. Best Pract Res Clin Obstet Gynaecol. 2020;65:18–31. https://doi.org/10.1016/j.bpobgyn.2019.11.006.

Article  PubMed  Google Scholar 

Ullah MF. Breast cancer: current perspectives on the disease status. Adv Exp Med Biol. 2019;1152:51–64. https://doi.org/10.1007/978-3-030-20301-6_4.

Article  CAS  Google Scholar 

Zhou W, Zeng X, Wu X. Effect of oleanolic acid on apoptosis and autophagy of SMMC-7721 hepatoma cells. Med Sci Monit. 2020;26:e921606. https://doi.org/10.12659/MSM.921606

Yin R, Li T, Tian JX, et al. Ursolic acid, a potential anticancer compound for breast cancer therapy. Crit Rev Food Sci Nutr. 2018;58:568–74. https://doi.org/10.1080/10408398.2016.1203755.

Article  CAS  PubMed  Google Scholar 

Iqbal J, Abbasi BA, Ahmad R, et al. Ursolic acid a promising candidate in the therapeutics of breast cancer: current status and future implications. Biomed Pharmacother. 2018;108:752–6. https://doi.org/10.1016/j.biopha.2018.09.096.

Article  CAS  PubMed  Google Scholar 

Eichhorn JM, Alford SE, Sakurikar N, et al. Molecular analysis of functional redundancy among anti-apoptotic Bcl-2 proteins and its role in cancer cell survival. Exp Cell Res. 2014;322:415–24. https://doi.org/10.1016/j.yexcr.2014.02.010.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kassi E, Sourlingas TG, Spiliotaki M, et al. Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Invest. 2009;27:723–33. https://doi.org/10.1080/07357900802672712.

Article  CAS  PubMed  Google Scholar 

Cocco S, Leone A, Piezzo M, et al. Targeting autophagy in breast cancer. Int J Mol Sci. 2020;21:7836. https://doi.org/10.3390/ijms21217836.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang Z, Zhang P, Jiang H, et al. Ursolic acid enhances the sensitivity of MCF-7 and MDA-MB-231 cells to epirubicin by modulating the autophagy pathway. Molecules. 2022;27:3399. https://doi.org/10.3390/molecules27113399.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu T, Song S, Wang X, et al. Small-molecule inhibitors of breast cancer-related targets: potential therapeutic agents for breast cancer. Eur J Med Chem. 2021;210: 112954. https://doi.org/10.1016/j.ejmech.2020.112954.

Article  CAS  PubMed  Google Scholar 

Meng Y, Lin ZM, Ge N, et al. Ursolic acid induces apoptosis of prostate cancer cells via the PI3K/Akt/mTOR pathway. Am J Chin Med. 2015;43:1471–86. https://doi.org/10.1142/S0192415X15500834.

Article  CAS  PubMed  Google Scholar 

Luo F, Zhao J, Liu S, et al. Ursolic acid augments the chemosensitivity of drug-resistant breast cancer cells to doxorubicin by AMPK-mediated mitochondrial dysfunction. Biochem Pharmacol. 2022;205: 115278. https://doi.org/10.1016/j.bcp.2022.115278.

Article  CAS  PubMed  Google Scholar 

Zhao C, Yin S, Dong Y, et al. Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. Autophagy. 2013;9:196–207. https://doi.org/10.4161/auto.22805.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang L, Yin Q, Liu C, et al. Nanoformulations of ursolic acid: a modern natural anticancer molecule. Front Pharmacol. 2021;12: 706121. https://doi.org/10.3389/fphar.2021.706121.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luo J, Hu YL, Wang H. Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-kappaB signaling pathways in vitro. Exp Ther Med. 2017;14:3623–31. https://doi.org/10.3892/etm.2017.4965.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kubatka P, Mazurakova A, Koklesova L et al. Salvia officinalis L. exerts oncostatic effects in rodent and in vitro models of breast carcinoma. Front Pharmacol. 2024;15:1216199. https://doi.org/10.3389/fphar.2024.1216199

Zhang R, Zhang Z, Xie L, et al. In vitro analysis of the molecular mechanisms of ursolic acid against ovarian cancer. BMC Complement Med Ther. 2025;25:65. https://doi.org/10.1186/s12906-025-04808-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang Y, Liu P, Jin Y, et al. A combined treatment with Ursolic acid and Solasodine inhibits colorectal cancer progression through the AKT1/ERK1/2-GSK-3beta-beta-catenin axis. Phytomedicine. 2024;135: 156068. https://doi.org/10.1016/j.phymed.2024.156068.

Article  CAS  PubMed  Google Scholar 

Kou B, Liu W, Xu X, et al. Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells. Oncol Rep. 2017;38:3137–43. https://doi.org/10.3892/or.2017.5988.

Article  CAS  PubMed  Google Scholar 

Kim SH, Son KM, Kim KY, et al. Deoxypodophyllotoxin induces cytoprotective autophagy against apoptosis via inhibition of PI3K/AKT/mTOR pathway in osteosarcoma U2OS cells. Pharmacol Rep. 2017;69:878–84. https://doi.org/10.1016/j.pharep.2017.04.007.

Article  CAS  PubMed  Google Scholar 

Wang X, Jiao X, Meng Y, et al. Methionine enkephalin (MENK) inhibits human gastric cancer through regulating tumor associated macrophages (TAMs) and PI3K/AKT/mTOR signaling pathway inside cancer cells. Int Immunopharmacol. 2018;65:312–22. https://doi.org/10.1016/j.intimp.2018.10.023.

Article  CAS  PubMed  Google Scholar 

Kim SM, Vetrivel P, Ha SE, et al. Apigetrin induces extrinsic apoptosis, autophagy and G2/M phase cell cycle arrest through PI3K/AKT/mTOR pathway in AGS human gastric cancer cell. J Nutr Biochem. 2020;83: 108427. https://doi.org/10.1016/j.jnutbio.2020.108427.

Article  CAS  PubMed  Google Scholar 

Zhang Y, Ma X, Li H, et al. Identifying the effect of ursolic acid against triple-negative breast cancer: coupling network pharmacology with experiments verification. Front Pharmacol. 2021;12: 685773. https://doi.org/10.3389/fphar.2021.685773.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li Z, Zhang X. Kinases involved in both autophagy and mitosis. Int J Mol Sci. 2017;18. https://doi.org/10.3390/ijms18091884

Platani M, Trinkle-Mulcahy L, Porter M, et al. Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes. J Cell Biol. 2015;210:45–62. https://doi.org/10.1083/jcb.201410001.

Article  CAS  PubMed  Google Scholar 

Villar VH, Vogler O, Barcelo F, et al. Down-regulation of AKT signalling by ursolic acid induces intrinsic apoptosis and sensitization to doxorubicin in soft tissue sarcoma. PLoS ONE. 2016;11: e0155946. https://doi.org/10.1371/journal.pone.0155946.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chuang WL, Lin PY, Lin HC, et al. The apoptotic effect of ursolic acid on SK-Hep-1 cells is regulated by the PI3K/Akt, p38 and JNK MAPK signaling pathways. Molecules. 2016;21:460. https://doi.org/10.3390/molecules21040460.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gai WT, Yu DP, Wang XS, et al. Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. Oncol Lett. 2016;12:2880–5. https://doi.org/10.3892/ol.2016.5015.

Article  CAS  PubMed  PubMed Central