Anticancer properties of berberine - analysis of the latest reports
DOI:
https://doi.org/10.12775/JEHS.2024.61.005Keywords
berberine, anticancer properties, anticancer medications, cancerAbstract
Introduction and purpose:
Berberine is a plant alkaloid that naturally occurs in the fruits of common barberry (Berberis vulgaris). This alkaloid has long been used in natural medicine. It exhibits a range of bioactivities, such as antioxidant, anti-inflammatory, antidiabetic, anti-edema, and antimicrobial actions. Through the promising therapeutic effects of berberine in metabolic syndrome, as well as its impact on carcinogenesis, this compound is beginning to play a significant role in preventive medicine. Recently, particular attention has been paid to the anticancer properties of berberine, which are based on many biochemical pathways, particularly its pro-apoptotic and anti-inflammatory action. The study aimed to review the anticancer mechanisms of berberine and summarize them about individual cancers.
State of knowledge:
The article reviews the current literature on the anticancer properties of berberine for individual cancers, focusing primarily on its molecular mechanisms of action. In addition, the potential of berberine as a promising candidate forming the basis for drug production and its use in preventive medicine was analyzed.
Summary:
In summary, many studies have shown that berberine exhibits anticancer activity in many types of cancers, including breast, lung, stomach, liver, colorectal, ovarian, cervical, and prostate cancers. Berberine inhibits the growth of cancer cells, limits metastases, induces apoptosis, stimulates autophagy, and enhances the effectiveness of anticancer drugs. Despite its potential as a promising candidate for drug production, there are currently no approved pure berberine preparations for the treatment of specific ailments. Research on its effectiveness and safety is still ongoing.
References
Och A, Podgórski R, Nowak R. Biological Activity of Berberine—A Summary Update. Toxins. 2020;12, 713. doi: 10.3390/toxins12110713.
Rauf A, Abu-Izneid T, Khalil AA, Imran M, Shah ZA, Emran TB, et al. Berberine as a potential anticancer agent: A comprehensive review. Molecules. 2021;26(23):7368. doi: 10.3390/molecules26237368.
Kim JB, Ko E, Han W, Shin I, Park SY, Noh DY. Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells. Planta Med. 2008;74(14):1693-700. doi: 10.1055/s-0028-1088313.
Xiong RG, Huang SY, Wu SX, et al. Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review. Molecules. 2022;27(14):4523. DOI: 10.3390/molecules27144523. PMID: 35889396; PMCID: PMC9316001.
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;25:506.
Lin YS, Chiu YC, Tsai YH, Tsai YF, Wang JY, Tseng LM, Chiu JH. Different mechanisms involved in the berberine-induced antiproliferation effects in triple-negative breast cancer cell lines. J Cell Biochem. 2019;120:13531–13544.
Zhao L, Zhang C. Berberine Inhibits MDA-MB-231 Cells by attenuating their inflammatory responses. BioMed Res Int. 2020;2020:3617514.
Farooqi AA, Qureshi MZ, Khalid S, Attar R, Martinelli C, Sabitaliyevich UY, Nurmurzayevich SB, Taverna S, Poltronieri P, Xu B. Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy. Cancers. 2019;11:478. doi: 10.3390/cancers11040478.
Refaat A, Abdelhamed S, Yagita H, Inoue H, Yokoyama S, Hayakawa Y, Saiki I. Berberine Enhances Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated Apoptosis in Breast Cancer. Oncol Lett. 2013;6:840–844. doi: 10.3892/ol.2013.1434.
Zheng X, Zhao Y, Jia Y, Shao D, Zhang F, Sun M, et al. Biomimetic co-assembled nanodrug of doxorubicin and berberine suppresses chemotherapy-exacerbated breast cancer metastasis. Biomaterials. 2021;271:120716. doi: 10.1016/j.biomaterials.2021.120716.
Chen YX, Gao QY, Zou TH, Wang BM, Liu SD, Sheng JQ, et al. Berberine versus placebo for the prevention of recurrence of colorectal adenoma: A multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol. 2020;5(3):267–75. doi: 10.1016/S2468-1253(19)30409-1.
Yan SH, Hu LM, Hao XH, Liu J, Tan XY, Geng ZR, et al. Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer. iScience. 2022;25(8):104773. doi: 10.1016/j.isci.2022.104773.
Liu X, Ji Q, Ye N, Sui H, Zhou L, Zhu H, et al. Berberine inhibits invasion and metastasis of colorectal cancer cells via COX-2/PGE2 mediated JAK2/STAT3 signaling pathway. PloS One. 2015;10(5):e0123478. doi: 10.1371/journal.pone.0123478.
Dai W, Mu L, Cui Y, Li Y, Chen P, Xie H, Wang X. Berberine promotes apoptosis of colorectal cancer via regulation of the long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2)/AU-binding factor 1 (AUF1)/B-cell CLL/lymphoma 2 (Bcl-2) axis. Med Sci Monitor. 2019;25:730.
Hu S, Zhao R, Liu Y, Chen J, Zheng Z, Wang S. Preventive and therapeutic roles of berberine in gastrointestinal cancers. BioMed Res Int. 2019;2019:6831520.
Liu H, Huang C, Wu L, Wen B. Effect of evodiamine and berberine on miR-429 as an oncogene in human colorectal cancer. Onco Targets Ther. 2016;9:4121.
Lü Y, Han B, Yu H, Cui Z, Li Z, Wang J. Berberine regulates the microRNA-21-ITGΒ4-PDCD4 axis and inhibits colon cancer viability. Oncol Lett. 2018;15:5971–5976.
Akula SM, Candido S, Libra M, Abrams SL, Steelman LS, Lertpiriyapong K, Ramazzotti G, Ratti S, Follo MY, Martelli AM, et al. Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells. Adv Biol Regul. 2019;73:100633.
Pinto-Garcia L, Efferth T, Torres A, Hoheisel JD, Youns M. Berberine inhibits cell growth and mediates caspase-independent cell death in human pancreatic cancer cells. Planta Med. 2010;76:1155–1161.
Zhang C, Yang T, Chen X, Xu J, Liang D, Yi H, Chen S, Huang L, Liu N, Lin S. A preliminary study on the synthetic lethal effect of berberine and olaparib on pancreatic cancer cells and its mechanism. In IE3S Web of Conferences. 2020;130:01013. doi: 10.1051/ie3sconf/202013001013.
Bobbili MR, Mader RM, Grillari J, Dellago H. OncomiR-17-5p: alarm signal in cancer? Oncotarget. 2017;8(41):71206–22. doi: 10.18632/oncotarget.19331.
Liu J, Luo X, Guo R, Jing W, Lu H. Cell metabolomics reveals berberine-inhibited pancreatic cancer cell viability and metastasis by regulating citrate metabolism. J Proteome Res. 2020;19:3825–3836.
Shapiro SD. Matrix metalloproteinase degradation of extracellular matrix: Biological consequences. Curr Opin Cell Biol. 1998;10:602–608.
Lin J, Yang J, Wu C, Lin S, Hsieh W, Lin M, Yu F, Yu C, Chen G, Chang Y, et al. Berberine induced down-regulation of matrix metalloproteinase-1, -2 and -9 in human gastric cancer cells (SNU-5) in vitro. In Vivo. 2008;22:223–230.
Wang J, Yang S, Cai X, Dong J, Chen Z, Wang R, et al. Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer. Oncotarget. 2016;7(46):76076–86. doi: 10.18632/oncotarget.12589.
Kou Y, Tong B, Wu W, Liao X, Zhao M. Berberine improves chemo-sensitivity to cisplatin by enhancing cell apoptosis and repressing PI3K/AKT/mTOR signaling pathway in gastric cancer. Front Pharmacol. 2020;11:616251. doi: 10.3389/fphar.2020.616251.
You HY, Xie XM, Zhang WJ, Zhu HL, Jiang FZ. Berberine modulates cisplatin sensitivity of human gastric cancer cells by upregulation of miR-In Vitro. Cell Dev Biol Anim. 2016;52:857–863.
Zhang Q, Wang X, Cao S, Sun Y, He X, Jiang B, Yu Y, Duan J, Qiu F, Kang N. Berberine represses human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt signaling pathways. Biomed Pharmacother. 2020;128:110245.
Li F, Dong X, Lin P, Jiang J. Regulation of Akt/FoxO3a/Skp2 axis is critically involved in berberine-induced cell cycle arrest in hepatocellular carcinoma cells. Int J Mol Sci. 2018;19:327.
Chuang TY, Wu HL, Min J, Diamond M, Azziz R, Chen YH. Berberine regulates the protein expression of multiple tumorigenesis-related genes in hepatocellular carcinoma cell lines. Cancer Cell Int. 2017;17:1–8.
Huang Y, Wang K, Gu C, Yu G, Zhao D, Mai W, Zhong Y, Liu S, Nie Y, Yang H. Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib. Oncol Rep. 2018;40:1525–1532.
Lin HJ, Ho JH, Tsai LC, Yang FY, Yang LL, Kuo CD, et al. Synthesis and In vitro photocytotoxicity of 9-/13-Lipophilic substituted berberine derivatives as potential anticancer agents. Molecules. 2020;25(3):677. doi: 10.3390/molecules25030677.
Kim JS, Oh D, Yim MJ, Park JJ, Kang KR, Cho IA, Moon SM, Oh JS, You JS, Kim CS. Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells. Oncol Rep. 2015;33:1775–1782.
Jin H, Jin X, Cao B, Wang W. Berberine affects osteosarcoma via downregulating the caspase-1/IL-1β signaling axis. Oncol Rep. 2017;37:729–736.
Hsu HK, Hsu KH, Cheng YM, Suen HY, Peng SF. Development and in vitro evaluation of linear PEI-shelled heparin/berberine nanoparticles in human osteosarcoma U-2 OS cells. Molecules. 2018;23:3121.
Luo X, Gu J, Zhu R, Feng M, Zhu X, Li Y, et al. Integrative analysis of differential miRNA and functional study of miR-21 by seed-targeting inhibition in multiple myeloma cells in response to berberine. BMC Syst Biol. 2014;8:82. doi: 10.1186/1752-0509-8-82.
Wang J, Qi Q, Feng Z, Zhang X, Huang B, Chen A, Prestegarden L, Li X, Wang J. Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway. Oncotarget. 2016;7(41):66944–58. doi: 10.18632/oncotarget.11396. PMID: 27531889; PMCID: PMC5342793.
Nasrollahzadeh E, Razi S, Keshavarz-Fathi M, Mazzone M, Rezaei N. Pro-tumorigenic functions of macrophages at the primary, invasive and metastatic tumor site. Cancer Immunol Immunother. 2020;69:1673–1697.
Tong L, Xie C, Wei Y, Qu Y, Liang H, Zhang Y, Xu T, Qian X, Qiu H, Deng H. Antitumor effects of berberine on gliomas via inactivation of caspase-1-mediated IL-1β and IL-18 release. Front Oncol. 2019;9:364.
Qu H, Song X, Song Z, Jiang X, Gao X, Bai L, et al. Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma. Cancer Cell Int. 2020;20(1):592. doi: 10.1186/s12935-020-01693-y.
Liu JF, Lai KC, Peng SF, Maraming P, Huang YP, Huang AC, Chueh FS, Huang WW, Chung JG. Berberine inhibits human melanoma AS2 cell migration and invasion via affecting the FAK, uPA, and NF-κB signaling pathways and inhibits PLX4032 resistant AS2 cell migration in vitro. Molecules. 2018;23:2019.
Li DX, Zhang J, Zhang Y, Zhao PW, Yang LM. Inhibitory effect of berberine on human skin squamous cell carcinoma A431 cells. Genet Mol Res. 2015;14:10553–10568.
Shah D, Challagundla N, Dave V, Patidar A, Saha B, Nivsarkar M, et al. Berberine mediates tumor cell death by skewing tumor-associated immunosuppressive macrophages to inflammatory macrophages. Phytomedicine. 2022;99:153904. doi: 10.1016/j.phymed.2021.153904.
Wang Y, Zhang S. Berberine suppresses growth and metastasis of endometrial cancer cells via miR-101/COX-2. Biomed Pharmacother. 2018;103:1287–1293.
Kuo HP, Lee YJ, Hsu CY, Lee SL, Hsu SC, Chuang TC, Liu JY, Kuo CL, Ho CT, Kao MC. Growth-suppressive effect of berberine on endometrial carcinoma cells: Role of mitochondrial and PI3K/Akt pathway. J Funct Foods. 2015;17:600–609.
Li Gh, Wang Dl, Hu Y, Pu P, Li Dz, Wang Wd, et al. Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy. Med Oncol. 2010;27(3):919–25. doi: 10.1007/s12032-009-9307-8.
Zhang Q, Zhang C, Yang X, Yang B, Wang J, Kang Y, Wang Z, Li D, Huang G, Ma Z. Berberine inhibits the expression of hypoxia induction factor-1alpha and increases the radiosensitivity of prostate cancer. Diagn Pathol. 2014.
Tian Y, Zhao L, Wang Y, Zhang H, Xu D, Zhao X, Li Y, Li J. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells. Asian J Androl. 2016;18:607.
Liu CH, Tang WC, Sia P, Huang CC, Yang PM, Wu MH, Lai IL, Lee KH. Berberine inhibits the metastatic ability of prostate cancer cells by suppressing epithelial-to-mesenchymal transition (EMT)-associated genes with predictive and prognostic relevance. Int J Biol Med Sci. 2015;12:63.
Park KS, Kim JB, Bae J, Park SY, Jee HG, Lee KE, Youn YK. Berberine inhibited the growth of thyroid cancer cell lines 8505C and TPC. Yonsei Med J. 2012;53:346–351.
Kumarasamy VM, Sun D. Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative. Int J Oncol. 2017;51:145–157.
Bernitsa S, Dayan R, Stephanou A, Tzvetanova ID, Patrikios IS. Natural biomolecules and derivatives as anticancer immunomodulatory agents. Front Immunol. 2023;DOI:10.3389/fimmu.2022.1070367.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Patrycja Rozwadowska, Piotr Bator, Michał Razik, Jan Ramian, Jakub Rybak, Barbara Magiera, Karol Magiera, Wiktor Razik
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 473
Number of citations: 0