|Table of Contents|

The role of berberine in proliferation,migration,apoptosis and autophagy of bladder cancer cells and its mechanism

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 03
Page:
367-374
Research Field:
Publishing date:

Info

Title:
The role of berberine in proliferation,migration,apoptosis and autophagy of bladder cancer cells and its mechanism
Author(s):
ZHAO YuwanGAO ShengMIAO BailiangQIU JingpingZHU LugangLIU Jianjun
Department of Urology,Affiliated Hospital of Guangdong Medical University,Guangdong Zhanjiang 524002,China.
Keywords:
berberinebladder cancerapoptosisautophagy
PACS:
R737.14
DOI:
10.3969/j.issn.1672-4992.2025.03.003
Abstract:
Objective:To explore the anticancer effect of berberine (BBR) in bladder cancer cells and its mechanism.Methods:The inhibitory effect of BBR on the proliferation of bladder cancer cells was analyzed by CCK-8 assay and clonal formation assay,the migration ability of bladder cancer cells was detected by scratch assay and transwell assay,apoptosis detection kit was used to detect the changes of apoptosis,MDC kit and electron microscope were used to detect the changes of intracellular autophagosomes.Western blot was used to analyze the changes of Cleaved-PARP,Bax,Cleaved-caspase 9,Cleaved-caspase 3,and Bcl2,LC3B,Beclin1,P62,P-AKT and P-mTOR protein levels.Results:CCK-8 and clonal formation experiments showed that BBR significantly inhibited the proliferation of bladder cancer cells.Both scratch and Transwell experiments showed that BBR could inhibit the growth of bladder cancer cells by inhibiting their migration ability.BBR could depolarize the mitochondrial membrane of bladder cancer cells and induced apoptosis of bladder cancer cells through Caspase cascade.The intracellular autophagosomes were observed by MDC staining and electron microscopy,and it was found that BBR promoted autophagy in bladder cancer cells.By analyzing the expression levels of autophagy related proteins,it was further confirmed that BBR induced autophagy in bladder cancer cells.The expression levels of P-AKT and P-mTOR decreased in bladder cancer cells treated with BBR,suggesting that BBR can inhibit cell growth by inhibiting the AKT/m-TOR pathway in bladder cancer cells.Conclusion:BBR can significantly inhibit the proliferation and migration of bladder cancer cells,and induce apoptosis and autophagy.Moreover,BBR can inhibit the growth of bladder cancer cells by inhibiting the AKT/mTOR signaling pathway.

References:

[1] BRAY F,LAVERSANNE M,SUNG H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J] .CA Cancer J Clin,2024,74(3):229-263.
[2] LOBO N,SHARIAT SF,GUO CC,et al.What is the significance of variant histology in urothelial carcinoma[J].Eur Urol Focus,2020,6(4):653-663.
[3] BERDIK C.Unlocking bladder cancer[J].Nature,2017,551(7679):S34-S35.
[4] WIGNER P,BIJAK M,SALUK-BIJAK J.The green anti-cancer weapon.The role of natural compounds in bladder cancer treatment[J].Int J Mol Sci,2021,22(15):7787.
[5] LIU D,MENG X,WU D,et al.A natural isoquinoline alkaloid with antitumor activity:Studies of the biological activities of berberine[J] .Front Pharmacol,2019,10:9.
[6] NEAG MA,MOCAN A,ECHEVERRIA J,et al.Berberine:Botanical occurrence,traditional uses,extraction methods,and relevance in cardiovascular,metabolic,hepatic,and renal disorders[J].Front Pharmacol,2018,9:557.
[7] XU Z,FENG W,SHEN Q,et al.Rhizoma coptidis and berberine as a natural drug to combat aging and aging-related diseases via anti-oxidation and AMPK activation[J].Aging Dis,2017,8(6):760-777.
[8] ZHENG X,ZHAO Y,JIA Y,et al.Biomimetic co-assembled nanodrug of doxorubicin and berberine suppresses chemotherapy-exacerbated breast cancer metastasis[J].Biomaterials,2021,271:120716.
[9] QI HW,XIN LY,XU X,et al.Epithelial-to-mesenchymal transition markers to predict response of berberine in suppressing lung cancer invasion and metastasis[J].J Transl Med,2014,12:22.
[10] ZHAO Y,YANG X,ZHAO J,et al.Berberine inhibits chemotherapy-exacerbated ovarian cancer stem cell-like characteristics and metastasis through GLI1[J].Eur J Pharmacol,2021,895:173887.
[11] DU H,GU J,PENG Q,et al.Berberine suppresses EMT in liver and gastric carcinoma cells through combination with TGFβR regulating TGF-β/Smad pathway[J].Oxid Med Cell Longev,2021,2021:2337818.
[12] OKUBO S,UTO T,GOTO A,et al.Berberine induces apoptotic cell death via activation of Caspase-3 and Caspase-8 in HL-60 human leukemia cells:Nuclear localization and structure-activity relationships[J].Am J Chin Med,2017,45(7):1497-1511.
[13] BOCK FJ,TAIT SWG.Mitochondria as multifaceted regulators of cell death[J].Nat Rev Mol Cell Biol,2020,21(2):85-100.
[14] HWANG J,KUO H,TSENG T,et al.Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells[J].Archives of Toxicology,2006,80(2):62-73.
[15] LOPES TZ,DE MORAES FR,TEDESCO AC,et al.Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells[J].Biomed Pharmacother,2020,125:110038.
[16] ZHANG Q,WANG X,CAO S,et al.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[J].Biomed Pharmacother,2020,128:110245.
[17] WANG R,LU X,YU R.Lycopene inhibits epithelial-mesenchymal transition and promotes apoptosis in oral cancer via PI3K/AKT/m-TOR signal pathway[J].Drug Des Devel Ther,2020,14:2461-2471.
[18] ZHANG DM,LIU JS,DENG LJ,et al.Arenobufagin,a natural bufadienolide from toad venom,induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway[J].Carcinogenesis,2013,34(6):1331-1342.
[19] LENIS AT,LEC PM,CHAMIE K,et al.Bladder cancer:A review[J].JAMA,2020,324(19):1980-1991.
[20] CARNEIRO BA,EL-DEIRY WS.Targeting apoptosis in cancer therapy[J].Nat Rev Clin Oncol,2020 17(7):395-417.
[21] GALLUZZI L,VITALEI I,AARONSON SA,et al.Molecular mechanisms of cell death:recommendations of the nomenclature committee on cell death 2018[J].Cell Death Differ,2018,25(3):486-541.
[22] LIU X,KIM CN,YANG J,et al.Induction of apoptotic program in cell-free extracts:requirement for dATP and cytochrome c[J].Cell,1996,86(1):147-157.
[23] KASHYAP D,GARG VK,GOEL N.Intrinsic and extrinsic pathways of apoptosis:Role in cancer development and prognosis[J].Adv Protein Chem Struct Biol,2021,125:73-120.
[24] LEVY JMM,TOWERS CG,THORBURN A.Targeting autophagy in cancer[J].Nat Rev Cancer,2017,17(9):528-542.
[25] PATEL NH,BLOUKH S,ALWOHOSH E,et al.Autophagy and senescence in cancer therapy[J].Adv Cancer Res,2021,150:1-74.
[26] FENG Y,HE D,YAO Z,et al.The machinery of macroautophagy[J].Cell Res,2014,24(1):24-41.
[27] GLICK D,BARTH S,MACLEOD KF.Autophagy:cellular and molecular mechanisms[J].J Pathol,2010,221(1):3-12.
[28] MIJALJICA D,PRESCOTT M,DEVENISH RJ.Microautophagy in mammalian cells:revisiting a 40-year-old conundrum[J].Autophagy,2011,7(7):673-682.
[29] WANG Y,LIU Y,DU X,et al.The anti-cancer mechanisms of berberine:A review[J].Cancer Manag Res,2020,12:695-702.
[30]JANEV A,RAMUTA TZ,JERMAN UD,et al.Human amniotic membrane inhibits migration and invasion of muscle-invasive bladder cancer urothelial cells by downregulating the FAK/PI3K/Akt/mTOR signalling pathway[J].Sci Rep,2023,13(1):19227.
[31] LUO S,HUANG X,LI S,et al.Homogeneous polyporus polysaccharide exerts anti-bladder cancer effects via autophagy induction[J].Pharm Biol,2024,62(1):214-221.

Memo

Memo:
-
Last Update: 1900-01-01