Review on the application of ginsenosides and their pharmaceutical preparations in the treatment of breast cancer
DOI:
https://doi.org/10.61173/s28x4j67Keywords:
Ginsenosides, Breast Cancer Treatment, Pharmaceutical PreparationsAbstract
Ginsenosides, as the main active ingredients of ginseng, have shown great potential in the treatment of breast cancer. Studies have found that many types of ginsenosides, such as PPD ginsenosides Rh2, Rg3, CK and PPT ginsenosides Rg1, Rg2, have inhibitory effects on breast cancer cells. These components can effectively inhibit the development of breast cancer by directly inhibiting the proliferation of cancer cells, inducing apoptosis, enhancing the anticancer ability of NK cells, and remodeling the tumor microenvironment. In addition, the liposome and nanoparticle drug delivery system synthesized by ginsenoside showed great advantages in the application of drug formulations, providing a new strategy for the targeted transportation of antitumor drugs and improving the tumor killing ability. These research results not only provide a new strategy for breast cancer treatment, but also expand the application prospect of ginsenosides in cancer treatment. In the future, with the in-depth research, ginsenosides and their pharmaceutical preparations are expected to play a greater role in the treatment of breast cancer and bring more hope to patients.
References
[1] Rausch WD, Liu S, Gille G, Radad K. Neuroprotective effects of ginsenosides. Acta Neurobiol Exp (Wars). 2006;66(4):369-75. doi: 10.55782/ane-2006-1625. PMID: 17265697.
[2] Qin SY, Lai JM, Jia B, Wang LQ, Li SS, Yan SK, Xiao X. [Research progress in preparations of Panax ginseng]. Zhongguo Zhong Yao Za Zhi. 2024 Apr;49(7):1717-1724. Chinese. doi: 10.19540/j.cnki.cjcmm.20231124.301. PMID: 38812184.
[3] Li SS, Jin YP, Yao CL, Wang YP. [Research achievements on structures and activities of polysaccharides from Panax ginseng]. Zhongguo Zhong Yao Za Zhi. 2014 Dec;39(24):4709- 15. Chinese. PMID: 25898565.
[4] Sun, Y.S., Zhao, Z., Yang, Z.N., Xu, F., Lu, H.J., Zhu, Z.Y., Shi, W., Jiang, J., Yao, P.P., Zhu, H.P. (2017). Risk Factors and Preventions of Breast Cancer. International Journal of Biological Sciences, 13(11), 1387-1397. https://doi.org/10.7150/ijbs.21635.
[5] Zheng RS, Chen R, Han BF, Wang SM, Li L, Sun KX, Zeng HM, Wei WW, He J. [Cancer incidence and mortality in China, 2022]. Zhonghua Zhong Liu Za Zhi. 2024 Mar 23;46(3):221- 231. Chinese. doi: 10.3760/cma.j.cn112152-20240119-00035. PMID: 38468501.
[6] Banthia P, Gambhir L, Sharma A, Daga D, Kapoor N, Chaudhary R, Sharma G. Nano to rescue: repository of nanocarriers for targeted drug delivery to curb breast cancer. 3 Biotech. 2022 Mar;12(3):70. doi: 10.1007/s13205-022-03121-6. Epub 2022 Feb 13. PMID: 35223356; PMCID: PMC8841383.
[7] Yao W, Guan Y. Ginsenosides in cancer: A focus on the regulation of cell metabolism. Biomed Pharmacother. 2022 Dec;156:113756. doi: 10.1016/j.biopha.2022.113756. Epub 2022 Oct 10. PMID: 36228372.
[8] Peng K, Luo T, Li J, Huang J, Dong Z, Liu J, Pi C, Zou Z, Gu Q, Liu O, Zhang JT, Luo ZY. Ginsenoside Rh2 inhibits breast cancer cell growth via ERβ-TNFα pathway. Acta Biochim Biophys Sin (Shanghai). 2022 May 25;54(5):647- 656. doi: 10.3724/abbs.2022039. PMID: 35593465; PMCID: PMC9828196.
[9] Jeong D, Ham J, Park S, Kim HW, Kim H, Ji HW, Kim SJ. Ginsenoside Rh2 Suppresses Breast Cancer Cell Proliferation by Dean&Francis Epigenetically Regulating the Long Noncoding RNA C3orf67- AS1. Am J Chin Med. 2019;47(7):1643-1658. doi: 10.1142/ S0192415X19500848. Epub 2019 Oct 23. PMID: 31645124.
[10] Park JE, Ji HW, Kim HW, Baek M, Jung S, Kim SJ. Ginsenoside Rh2 Regulates the CFAP20DC-AS1/MicroRNA- 3614-3p/BBX and TNFAIP3 Axis to Induce Apoptosis in Breast Cancer Cells. Am J Chin Med. 2022;50(6):1703-1717. doi: 10.1142/S0192415X22500720. Epub 2022 Jul 4. PMID: 35787669.
[11] Hou JG, Jeon BM, Yun YJ, Cui CH, Kim SC. Ginsenoside Rh2 Ameliorates Doxorubicin-Induced Senescence Bystander Effect in Breast Carcinoma Cell MDA-MB-231 and Normal Epithelial Cell MCF-10A. Int J Mol Sci. 2019 Mar 12;20(5):1244. doi: 10.3390/ijms20051244. PMID: 30871042; PMCID: PMC6429443.
[12] Hong C, Wang A, Xia J, Liang J, Zhu Y, Wang D, Zhan H, Feng C, Jiang X, Pan J, Wang J. Ginsenoside Rh2-Based Multifunctional Liposomes for Advanced Breast Cancer Therapy. Int J Nanomedicine. 2024 Mar 20;19:2879-2888. doi: 10.2147/ IJN.S437733. PMID: 38525007; PMCID: PMC10961064.
[13] Ning JY, Zhang ZH, Zhang J, Liu YM, Li GC, Wang AM, Li Y, Shan X, Wang JH, Zhang X, Zhao Y. Ginsenoside Rg3 decreases breast cancer stem-like phenotypes through impairing MYC mRNA stability. Am J Cancer Res. 2024 Feb 15;14(2):601-615. doi: 10.62347/GYXE7741. PMID: 38455405; PMCID: PMC10915333.
[14] Wu H, Wei G, Luo L, Li L, Gao Y, Tan X, Wang S, Chang H, Liu Y, Wei Y, Song J, Zhang Z, Huo J. Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody. Biomater Res. 2022 Dec 9;26(1):77. doi: 10.1186/s40824-022- 00329-8. PMID: 36494759; PMCID: PMC9733157.
[15] Hou M, Wang R, Zhao S, Wang Z. Ginsenosides in Panax genus and their biosynthesis. Acta Pharm Sin B. 2021 Jul;11(7):1813-1834. doi: 10.1016/j.apsb.2020.12.017. Epub 2021 Jan 2. PMID: 34386322; PMCID: PMC8343117.
[16] Fan M, Shan M, Lan X, Fang X, Song D, Luo H, Wu D. Anti-cancer effect and potential microRNAs targets of ginsenosides against breast cancer. Front Pharmacol. 2022 Oct 5;13:1033017. doi: 10.3389/fphar.2022.1033017. PMID: 36278171; PMCID: PMC9581320.
[17] Hou M, Wang R, Zhao S, Wang Z. Ginsenosides in Panax genus and their biosynthesis. Acta Pharm Sin B. 2021 Jul;11(7):1813-1834. doi: 10.1016/j.apsb.2020.12.017. Epub 2021 Jan 2. PMID: 34386322; PMCID: PMC8343117.
[18] Song JH, Eum DY, Park SY, Jin YH, Shim JW, Park SJ, Kim MY, Park SJ, Heo K, Choi YJ. Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells. PLoS One. 2020 Oct 22;15(10):e0240533. doi: 10.1371/journal. pone.0240533. PMID: 33091036; PMCID: PMC7580975.
[19] Rahimi S, van Leeuwen D, Roshanzamir F, Pandit S, Shi L, Sasanian N, Nielsen J, Esbjörner EK, Mijakovic I. Ginsenoside Rg3 Reduces the Toxicity of Graphene Oxide Used for pH- Responsive Delivery of Doxorubicin to Liver and Breast Cancer Cells. Pharmaceutics. 2023 Jan 24;15(2):391. doi: 10.3390/pharmaceutics15020391. PMID: 36839713; PMCID: PMC9965446.
[20] Jeong SM, Lee JH, Kim JH, Lee BH, Yoon IS, Lee JH, Kim DH, Rhim H, Kim Y, Nah SY. Stereospecificity of ginsenoside Rg3 action on ion channels. Mol Cells. 2004 Dec 31;18(3):383- 9. PMID: 15650337.
[21] Park EH, Kim YJ, Yamabe N, Park SH, Kim HK, Jang HJ, Kim JH, Cheon GJ, Ham J, Kang KS. Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell. J Ginseng Res. 2014 Jan;38(1):22-7. doi: 10.1016/j.jgr.2013.11.007. Epub 2013 Dec 11. PMID: 24558306; PMCID: PMC3915326.
[22] Nakhjavani M, Smith E, Palethorpe HM, Tomita Y, Yeo K, Price TJ, Townsend AR, Hardingham JE. Anti-Cancer Effects of an Optimised Combination of Ginsenoside Rg3 Epimers on Triple Negative Breast Cancer Models. Pharmaceuticals (Basel). 2021 Jun 30;14(7):633. doi: 10.3390/ph14070633. PMID: 34208799; PMCID: PMC8308773.
[23] Nakhjavani M, Palethorpe HM, Tomita Y, Smith E, Price TJ, Yool AJ, Pei JV, Townsend AR, Hardingham JE. Stereoselective Anti-Cancer Activities of Ginsenoside Rg3 on Triple Negative Breast Cancer Cell Models. Pharmaceuticals (Basel). 2019 Aug 1;12(3):117. doi: 10.3390/ph12030117. PMID: 31374984; PMCID: PMC6789838.
[24] Zhang B, Fu R, Duan Z, Shen S, Zhu C, Fan D. Ginsenoside CK induces apoptosis in triple-negative breast cancer cells by targeting glutamine metabolism. Biochem Pharmacol. 2022 Aug;202:115101. doi: 10.1016/j.bcp.2022.115101. Epub 2022 May 23. PMID: 35618001.
[25] Siraj FM, SathishKumar N, Kim YJ, Kim SY, Yang DC. Ginsenoside F2 possesses anti-obesity activity via binding with PPARγ and inhibiting adipocyte differentiation in the 3T3-L1 cell line. J Enzyme Inhib Med Chem. 2015 Feb;30(1):9-14. doi: 10.3109/14756366.2013.871006. Epub 2014 Mar 25. PMID: 24666293.
[26] Li C, Gou X, Gao H. Doxorubicin nanomedicine based on ginsenoside Rg1 with alleviated cardiotoxicity and enhanced antitumor activity. Nanomedicine (Lond). 2021 Dec;16(29):2587-2604. doi: 10.2217/nnm-2021-0329. Epub 2021 Nov 1. PMID: 34719938.
[27] Liu S, Huang J, Gao F, Yin Z, Zhang R. Ginsenoside RG1 augments doxorubicin-induced apoptotic cell death in MDA- MB-231 breast cancer cell lines. J Biochem Mol Toxicol. 2022 Jan;36(1):e22945. doi: 10.1002/jbt.22945. Epub 2021 Nov 16. PMID: 34783124.
[28] Chu Y, Zhang W, Kanimozhi G, Brindha GR, Tian D. Ginsenoside Rg1 Induces Apoptotic Cell Death in Triple- Negative Breast Cancer Cell Lines and Prevents Carcinogen- Dean&Francis Induced Breast Tumorigenesis in Sprague Dawley Rats. Evid Based Complement Alternat Med. 2020 Oct 23;2020:8886955. doi: 10.1155/2020/8886955. PMID: 33178325; PMCID: PMC7607905.
[29] Jeon H, Jin Y, Myung CS, Heo KS. Ginsenoside-Rg2 exerts anti-cancer effects through ROS-mediated AMPK activation associated mitochondrial damage and oxidation in MCF-7 cells. Arch Pharm Res. 2021 Jul;44(7):702-712. doi: 10.1007/s12272- 021-01345-3. Epub 2021 Jul 24. PMID: 34302638.
[30] Liu G, Zhang J, Sun F, Ma J, Qi X. Ginsenoside Rg2 Attenuated Trastuzumab-Induced Cardiotoxicity in Rats. Biomed Res Int. 2022 Jan 12;2022:8866660. doi: 10.1155/2022/8866660. PMID: 35071601; PMCID: PMC8769853.
[31] Lahiani MH, Eassa S, Parnell C, Nima Z, Ghosh A, Biris AS, Khodakovskaya MV. Carbon nanotubes as carriers of Panax ginseng metabolites and enhancers of ginsenosides Rb1 and Rg1 anti-cancer activity. Nanotechnology. 2017 Jan 6;28(1):015101. doi: 10.1088/0957-4484/28/1/015101. Epub 2016 Nov 28. PMID: 27893436.
[32] Lu L, Ao H, Fu J, Li M, Guo Y, Guo Y, Han M, Shi R, Wang X. Ginsenoside Rb1 stabilized and paclitaxel / protopanaxadiol co-loaded nanoparticles for synergistic treatment of breast tumor. Biomed Pharmacother. 2023 Jul;163:114870. doi: 10.1016/ j.biopha.2023.114870. Epub 2023 May 13. PMID: 37187019.
[33] Zuo S, Wang J, An X, Wang Z, Zheng X, Zhang Y. Fabrication of Ginsenoside-Based Nanodrugs for Enhanced Antitumor Efficacy on Triple-Negative Breast Cancer. Front Bioeng Biotechnol. 2022 Aug 12;10:945472. doi: 10.3389/ fbioe.2022.945472. PMID: 36032706; PMCID: PMC9412961.
[34] Gu H, Shi R, Xu C, Lv W, Hu X, Xu C, Pan Y, He X, Wu A, Li J. EGFR-Targeted Liposomes Combined with Ginsenoside Rh2 Inhibit Triple-Negative Breast Cancer Growth and Metastasis. Bioconjug Chem. 2023 Jun 21;34(6):1157-1165. doi: 10.1021/acs.bioconjchem.3c00207. Epub 2023 May 26. PMID: 37235785.
[35] Yang C, Qian C, Zheng W, Dong G, Zhang S, Wang F, Wei Z, Xu Y, Wang A, Zhao Y, Lu Y. Ginsenoside Rh2 enhances immune surveillance of natural killer (NK) cells via inhibition of ERp5 in breast cancer. Phytomedicine. 2024 Jan;123:155180. doi: 10.1016/j.phymed.2023.155180. Epub 2023 Nov 10. PMID: 38043385.
[36] Park JE, Kim HW, Yun SH, Kim SJ. Ginsenoside Rh2 upregulates long noncoding RNA STXBP5-AS1 to sponge microRNA-4425 in suppressing breast cancer cell proliferation. J Ginseng Res. 2021 Nov;45(6):754-762. doi: 10.1016/ j.jgr.2021.08.006. Epub 2021 Aug 27. PMID: 34764730; PMCID: PMC8570952.
[37] Kim YJ, Perumalsamy H, Castro-Aceituno V, Kim D, Markus J, Lee S, Kim S, Liu Y, Yang DC. Photoluminescent And Self-Assembled Hyaluronic Acid-Zinc Oxide-Ginsenoside Rh2 Nanoparticles And Their Potential Caspase-9 Apoptotic Mechanism Towards Cancer Cell Lines. Int J Nanomedicine. 2019 Oct 9;14:8195-8208. doi: 10.2147/IJN.S221328. PMID: 31632027; PMCID: PMC6790350.
[38] Hong C, Liang J, Xia J, Zhu Y, Guo Y, Wang A, Lu C, Ren H, Chen C, Li S, Wang D, Zhan H, Wang J. One Stone Four Birds: A Novel Liposomal Delivery System Multi-functionalized with Ginsenoside Rh2 for Tumor Targeting Therapy. Nanomicro Lett. 2020 Jun 16;12(1):129. doi: 10.1007/s40820-020-00472-8. PMID: 34138128; PMCID: PMC7770862.
[39] Jin Y, Huynh DTN, Heo KS. Ginsenoside Rh1 inhibits tumor growth in MDA-MB-231 breast cancer cells via mitochondrial ROS and ER stress-mediated signaling pathway. Arch Pharm Res. 2022 Mar;45(3):174-184. doi: 10.1007/s12272-022-01377- 3. Epub 2022 Mar 24. PMID: 35325393.
[44] Zheng W, Shen P, Yu C, Tang Y, Qian C, Yang C, Gao M, Wu Y, Yu S, Tang W, Wan G, Wang A, Lu Y, Zhao Y. Ginsenoside Rh1, a novel casein kinase II subunit alpha (CK2α) inhibitor, retards metastasis via disrupting HHEX/CCL20 signaling cascade involved in tumor cell extravasation across endothelial barrier. Pharmacol Res. 2023 Dec;198:106986. doi: 10.1016/j.phrs.2023.106986. Epub 2023 Nov 7. PMID: 37944834.
[40] Jin Y, Huynh DTN, Myung CS, Heo KS. Ginsenoside Rh1 Prevents Migration and Invasion through Mitochondrial ROS- Mediated Inhibition of STAT3/NF-κB Signaling in MDA- MB-231 Cells. Int J Mol Sci. 2021 Sep 28;22(19):10458. doi: 10.3390/ijms221910458. PMID: 34638797; PMCID: PMC8508665.
[41] Huynh DTN, Jin Y, Myung CS, Heo KS. Ginsenoside Rh1 Induces MCF-7 Cell Apoptosis and Autophagic Cell Death through ROS-Mediated Akt Signaling. Cancers (Basel). 2021 Apr 15;13(8):1892. doi: 10.3390/cancers13081892. PMID: 33920802; PMCID: PMC8071122.
[42] Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee J, Cho JY. Pharmacological potential of ginseng and its major component ginsenosides. J Ginseng Res. 2021 Mar;45(2):199- 210. doi: 10.1016/j.jgr.2020.02.004. Epub 2020 Mar 25. PMID: 33841000; PMCID: PMC8020288.
[43] Jiang RY, Fang ZR, Zhang HP, Xu JY, Zhu JY, Chen KY, Wang W, Jiang X, Wang XJ. Ginsenosides: changing the basic hallmarks of cancer cells to achieve the purpose of treating breast cancer. Chin Med. 2023 Sep 25;18(1):125. doi: 10.1186/s13020- 023-00822-9. PMID: 37749560; PMCID: PMC10518937.
[44] Jin Y, Huynh DTN, Nguyen TLL, Jeon H, Heo KS. Therapeutic effects of ginsenosides on breast cancer growth and metastasis. Arch Pharm Res. 2020 Aug;43(8):773-787. doi: 10.1007/s12272-020-01265-8. Epub 2020 Aug 24. PMID: 32839835.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 by the authors.
This work is licensed under a Creative Commons Attribution 4.0 International License.
