Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Berbamine Inhibits the Biological Activities of Prostate Cancer Cells by Modulating the ROS/NF-κB Axis

Author(s): Wanli Zhao, Yuqing Jiang, Xiaopeng Jia, Xiuli Wang and Yuexian Guo*

Volume 23, Issue 14, 2023

Published on: 01 June, 2023

Page: [1626 - 1633] Pages: 8

DOI: 10.2174/1871520623666230503094540

Price: $65

Abstract

Background/Introduction: Prostate cancer ranks as the second leading cause of cancer death. No effective pharmacological agent is available for prostate cancer treatment. Berbamine is an alkaloid extracted from the Chinese herb berberis, which exerts an effect on inhibiting cancer cell proliferation.

Objective: This study aimed to explore the mechanism of berbamine in inhibiting prostate cancer.

Methods: Prostate cancer cell lines PC-3 and DU145 cells were used to evaluate the effects of berbamine. Cell viability was determined using cell-counting kit 8. The intracellular reactive oxygen species (ROS) levels were measured using a ROS assay kit. Cell apoptosis rate was examined using flow cytometry. The protein levels associated with cell proliferation, NF-κB pathway, and apoptosis were determined using western blot.

Results: It was found that berbamine induced cell cycle arrest in the S phase and inhibited prostate cancer cell growth and proliferation. Berbamine inhibited prostate cancer cells by inhibiting the activation of the NF-κB pathway in vitro. Berbamine increased ROS as an upstream molecule that inhibited the NF-κB pathway.

Conclusion: Our results demonstrated that berbamine can effectively reduce the proliferation of prostate cancer cells. The ROS/NF-κB axis plays a crucial role in berbamine-mediated anti-prostate cancer cell proliferation.

« Previous Next »
Graphical Abstract

[1]
Gandaglia, G.; Leni, R.; Bray, F.; Fleshner, N.; Freedland, S.J.; Kibel, A.; Stattin, P.; Van Poppel, H.; La Vecchia, C. Epidemiology and prevention of prostate cancer. Eur. Urol. Oncol., 2021, 4(6), 877-892.
[http://dx.doi.org/10.1016/j.euo.2021.09.006] [PMID: 34716119]
[2]
Giona, S. The Epidemiology of Prostate Cancer. In: Prostate Cancer, Bott, S. R. J.; Ng, K. L., Eds. Exon publications: Brisbane (AU), 2021.
[3]
Michaelson, M.D.; Cotter, S.E.; Gargollo, P.C.; Zietman, A.L.; Dahl, D.M.; Smith, M.R. Management of complications of prostate cancer treatment. CA Cancer J. Clin., 2008, 58(4), 196-213.
[http://dx.doi.org/10.3322/CA.2008.0002] [PMID: 18502900]
[4]
Trewartha, D.; Carter, K. Advances in prostate cancer treatment. Nat. Rev. Drug Discov., 2013, 12(11), 823-824.
[http://dx.doi.org/10.1038/nrd4068] [PMID: 24172327]
[5]
Farooqi, A.A.; Wen, R.; Attar, R.; Taverna, S.; Butt, G.; Xu, B. Regulation of cell-signaling pathways by berbamine in different cancers. Int. J. Mol. Sci., 2022, 23(5), 2758.
[http://dx.doi.org/10.3390/ijms23052758] [PMID: 35269900]
[6]
Duan, H.; Luan, J.; Liu, Q.; Yagasaki, K.; Zhang, G. Suppression of human lung cancer cell growth and migration by berbamine. Cytotechnology, 2010, 62(4), 341-348.
[http://dx.doi.org/10.1007/s10616-009-9240-x] [PMID: 19967402]
[7]
Zhao, X.; He, Z.; Wu, D.; Xu, R. Berbamine selectively induces apoptosis of human acute promyelocytic leukemia cells via survivin-mediated pathway. Chin. Med. J., 2007, 120(9), 802-806.
[http://dx.doi.org/10.1097/00029330-200705010-00012] [PMID: 17531122]
[8]
Zhao, Y.; Tan, Y.; Wu, G.; Liu, L.; Wang, Y.; Luo, Y.; Shi, J.; Huang, H. Berbamine overcomes imatinib-induced neutropenia and permits cytogenetic responses in Chinese patients with chronic-phase chronic myeloid leukemia. Int. J. Hematol., 2011, 94(2), 156-162.
[http://dx.doi.org/10.1007/s12185-011-0887-7] [PMID: 21728004]
[9]
Nam, S.; Xie, J.; Perkins, A.; Ma, Y.; Yang, F.; Wu, J.; Wang, Y.; Xu, R.; Huang, W.; Horne, D.A.; Jove, R. Novel synthetic derivatives of the natural product berbamine inhibit Jak2/Stat3 signaling and induce apoptosis of human melanoma cells. Mol. Oncol., 2012, 6(5), 484-493.
[http://dx.doi.org/10.1016/j.molonc.2012.05.002] [PMID: 22717603]
[10]
Meng, Z.; Li, T.; Ma, X.; Wang, X.; Van Ness, C.; Gan, Y.; Zhou, H.; Tang, J.; Lou, G.; Wang, Y.; Wu, J.; Yen, Y.; Xu, R.; Huang, W. Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca2/calmodulin-dependent protein kinase II. Mol. Cancer Ther., 2013, 12(10), 2067-2077.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0314] [PMID: 23960096]
[11]
Wang, S.; Liu, Q.; Zhang, Y.; Liu, K.; Yu, P.; Liu, K.; Luan, J.; Duan, H.; Lu, Z.; Wang, F.; Wu, E.; Yagasaki, K.; Zhang, G. Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action. Mol. Cancer, 2009, 8(1), 81.
[http://dx.doi.org/10.1186/1476-4598-8-81] [PMID: 19796390]
[12]
Zhang, H.; Jiao, Y.; Shi, C.; Song, X.; Chang, Y.; Ren, Y.; Shi, X. Berbamine suppresses cell viability and induces apoptosis in colorectal cancer via activating p53-dependent apoptotic signaling pathway. Cytotechnology, 2018, 70(1), 321-329.
[http://dx.doi.org/10.1007/s10616-017-0146-8] [PMID: 28965196]
[13]
D’Autréaux, B.; Toledano, M.B. ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis. Nat. Rev. Mol. Cell Biol., 2007, 8(10), 813-824.
[http://dx.doi.org/10.1038/nrm2256] [PMID: 17848967]
[14]
Ingham, M.; Schwartz, G.K. Cell-cycle therapeutics come of age. J. Clin. Oncol., 2017, 35(25), 2949-2959.
[http://dx.doi.org/10.1200/JCO.2016.69.0032] [PMID: 28580868]
[15]
McLaughlin, F.; Finn, P.; La Thangue, N.B. The cell cycle, chromatin and cancer: Mechanism-based therapeutics come of age. Drug Discov. Today, 2003, 8(17), 793-802.
[http://dx.doi.org/10.1016/S1359-6446(03)02792-2] [PMID: 12946642]
[16]
Stein, S.J. Baldwin, A.S. NF-κB suppresses ROS levels in BCR-ABL+ cells to prevent activation of JNK and cell death. Oncogene, 2011, 30(45), 4557-4566.
[http://dx.doi.org/10.1038/onc.2011.156] [PMID: 21625221]
[17]
Liu, J.Y.; Zeng, Q.H.; Cao, P.G.; Xie, D.; Chen, X.; Yang, F.; He, L.Y.; Dai, Y.B.; Li, J.J.; Liu, X.M.; Zeng, H.L.; Zhu, Y.X.; Gong, L.; Cheng, Y.; Zhou, J.D.; Hu, J.; Bo, H.; Xu, Z.Z.; Cao, K. RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway. Br. J. Cancer, 2018, 118(12), 1617-1627.
[http://dx.doi.org/10.1038/s41416-018-0116-8] [PMID: 29867225]
[18]
Wei, Y.L.; Liang, Y.; Xu, L.; Zhao, X.Y. The antiproliferation effect of berbamine on k562 resistant cells by inhibiting NF-kappaB pathway. Anat. Rec., 2009, 292(7), 945-950.
[http://dx.doi.org/10.1002/ar.20924] [PMID: 19548306]
[19]
Liang, Y.; Xu, R.; Zhang, L.; Zhao, X. Berbamine, a novel nuclear factor κB inhibitor, inhibits growth and induces apoptosis in human myeloma cells. Acta Pharmacol. Sin., 2009, 30(12), 1659-1665.
[http://dx.doi.org/10.1038/aps.2009.167] [PMID: 19960011]
[20]
Liang, Y.; He, X.; Li, X.; Zhang, X.; Zhang, X.; Zhang, L.; Qiu, X.; Zhao, X.; Xu, R. 4-Chlorbenzoyl berbamine, a novel derivative of the natural product berbamine, potently inhibits the growth of human myeloma cells by modulating the NF-κB and JNK signalling pathways. Cancer Invest., 2016, 34(10), 496-505.
[http://dx.doi.org/10.1080/07357907.2016.1235709] [PMID: 27768381]
[21]
Kleih, M.; Böpple, K.; Dong, M.; Gaißler, A.; Heine, S.; Olayioye, M.A.; Aulitzky, W.E.; Essmann, F. Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis., 2019, 10(11), 851.
[http://dx.doi.org/10.1038/s41419-019-2081-4] [PMID: 31699970]
[22]
Reshetnikov, V.; Daum, S.; Janko, C.; Karawacka, W.; Tietze, R.; Alexiou, C.; Paryzhak, S.; Dumych, T.; Bilyy, R.; Tripal, P.; Schmid, B.; Palmisano, R.; Mokhir, A. ROS-Responsive N-Alkylaminoferrocenes for cancer-cell-specific targeting of mitochondria. Angew. Chem. Int. Ed., 2018, 57(37), 11943-11946.
[http://dx.doi.org/10.1002/anie.201805955] [PMID: 30035345]
[23]
Zeng, L.; Li, Y.; Li, T.; Cao, W.; Yi, Y.; Geng, W.; Sun, Z.; Xu, H. Selenium-platinum coordination compounds as novel anticancer drugs: selectively killing cancer cells via a reactive oxygen species (ROS)-mediated apoptosis route. Chem. Asian J., 2014, 9(8), 2295-2302.
[http://dx.doi.org/10.1002/asia.201402256] [PMID: 24844800]
[24]
Kirkwood, N.K.; O’Reilly, M.; Derudas, M.; Kenyon, E.J.; Huckvale, R.; van Netten, S.M.; Ward, S.E.; Richardson, G.P.; Kros, C.J. d-tubocurarine and berbamine: Alkaloids that are permeant blockers of the hair cell’s mechano-electrical transducer channel and protect from aminoglycoside toxicity. Front. Cell. Neurosci., 2017, 11, 262.
[http://dx.doi.org/10.3389/fncel.2017.00262] [PMID: 28928635]
[25]
He, Z.W.; Zhao, X.Y.; Xu, R.Z.; Wu, D. Effects of berbamine on growth of leukemia cell line NB4 and its mechanism. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2006, 35(2), 209-214.
[PMID: 16610091]
[26]
Wei, Y.L.; Xu, L.; Zhao, X.Y. Mechanism related to inhibition of leukemia K562 cells by berbamine. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2009, 38(4), 387-391.
[PMID: 19693977]
[27]
Yu, B.; Liu, L.; Yan, J.; Cao, J.; Cao, Y. Effect of berbamine on invasion and metastasis of human liver cancer SMMC-7721 cells and its possible mechanism. Anticancer Drugs, 2022, 33(1), e178-e185.
[http://dx.doi.org/10.1097/CAD.0000000000001179] [PMID: 34321418]
[28]
Zhang, C.M.; Gao, L.; Zheng, Y.J.; Yang, H.T. Berbamine increases myocardial contractility via a Ca2+-independent mechanism. J. Cardiovasc. Pharmacol., 2011, 58(1), 40-48.
[http://dx.doi.org/10.1097/FJC.0b013e31821b70d1] [PMID: 21753257]
[29]
Liu, L.; Xu, Z.; Yu, B.; Tao, L.; Cao, Y. Berbamine inhibits cell proliferation and migration and induces cell death of lung cancer cells via regulating c-Maf, PI3K/Akt, and MDM2-P53 pathways. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-20.
[http://dx.doi.org/10.1155/2021/5517143] [PMID: 34306137]
[30]
Wang, G.Y.; Lv, Q.H.; Dong, Q.; Xu, R.Z.; Dong, Q.H. Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice. J. Asian Nat. Prod. Res., 2009, 11(3), 219-228.
[http://dx.doi.org/10.1080/10286020802675076] [PMID: 19408145]
[31]
Wang, Z.; Guo, H.Y.; Huang, Y.L. Escopoletin treatment induces apoptosis and arrests cell cycle at G0/G1 phase in the oral squamous cancer cell lines. Int. J. Clin. Exp. Med., 2015, 8(7), 11496-11501.
[PMID: 26379969]
[32]
Yamamoto, T.; Nishita, T.; Taga, A. Dark colored maple syrup treatment induces S phase cell cycle arrest via reduced proliferating cell nuclear antigen expression in colorectal cancer cells. Oncol. Lett., 2019, 17(3), 2713-2720.
[http://dx.doi.org/10.3892/ol.2019.9928] [PMID: 30854045]
[33]
Izzo, J.G.; Wu, X.; Wu, T.T.; Huang, P.; Lee, J.S.; Liao, Z.; Lee, J.H.; Bhutani, M.S.; Hofstetter, W.; Maru, D.; Hung, M.C.; Ajani, J.A. Therapy-induced expression of NF-κB portends poor prognosis in patients with localized esophageal cancer undergoing preoperative chemoradiation. Dis. Esophagus, 2009, 22(2), 127-132.
[http://dx.doi.org/10.1111/j.1442-2050.2008.00884.x] [PMID: 19021681]
[34]
Kuo, S.H.; Yang, S.H.; Wei, M.F.; Lee, H.W.; Tien, Y.W.; Cheng, A.L.; Yeh, K.H. Contribution of nuclear BCL10 expression to tumor progression and poor prognosis of advanced and/or metastatic pancreatic ductal adenocarcinoma by activating NF-κB-related signaling. Cancer Cell Int., 2021, 21(1), 436.
[http://dx.doi.org/10.1186/s12935-021-02143-z] [PMID: 34412631]
[35]
Lin, G.; Zheng, X.; Li, C.; Chen, Q.; Ye, Y. KRAS mutation and NF-κB activation indicates tolerance of chemotherapy and poor prognosis in colorectal cancer. Dig. Dis. Sci., 2012, 57(9), 2325-2333.
[http://dx.doi.org/10.1007/s10620-012-2172-x] [PMID: 22526587]
[36]
Lee, S.H.; Son, S.M.; Son, D.J.; Kim, S.M.; Kim, T.J.; Song, S.; Moon, D.C.; Lee, H.W.; Ryu, J.C.; Yoon, D.Y.; Hong, J.T. Epothilones induce human colon cancer SW620 cell apoptosis via the tubulin polymerization-independent activation of the nuclear factor-κB/IκB kinase signal pathway. Mol. Cancer Ther., 2007, 6(10), 2786-2797.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-0002] [PMID: 17938270]
[37]
Péant, B.; Diallo, J.S.; Dufour, F.; Le Page, C.; Delvoye, N.; Saad, F.; Mes-Masson, A.M. Over-expression of IκB-kinase-ε (IKKε/IKKi) induces secretion of inflammatory cytokines in prostate cancer cell lines. Prostate, 2009, 69(7), 706-718.
[http://dx.doi.org/10.1002/pros.20912] [PMID: 19170126]
[38]
Parrondo, R. Pozas, A.; Reiner, T.; Rai, P.; Perez-Stable, C. NF-κB activation enhances cell death by antimitotic drugs in human prostate cancer cells. Mol. Cancer, 2010, 9(1), 182.
[http://dx.doi.org/10.1186/1476-4598-9-182] [PMID: 20618955]
[39]
Yu, J.; Jin, J.; Li, Y. The physiological functions of IKK-selective substrate identification and their critical roles in diseases. STEMedicine, 2020, 1(4)e49
[http://dx.doi.org/10.37175/stemedicine.v1i4.49]
[40]
Liu, L.; Yin, S.; Brobbey, C.; Gan, W. Ubiquitination in cancer stem cell: Roles and targeted cancer therapy. STEMedicine, 2020, 1(3)e37
[http://dx.doi.org/10.37175/stemedicine.v1i3.37]
[41]
Misra, U.K.; Deedwania, R.; Pizzo, S.V. Activation and cross-talk between Akt, NF-kappaB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78. J. Biol. Chem., 2006, 281(19), 13694-13707.
[http://dx.doi.org/10.1074/jbc.M511694200] [PMID: 16543232]
[42]
Zhao, Y.; Lv, J.J.; Chen, J.; Jin, X.B.; Wang, M.W.; Su, Z.H.; Wang, L.Y.; Zhang, H.Y. Berbamine inhibited the growth of prostate cancer cells in vivo and in vitro via triggering intrinsic pathway of apoptosis. Prostate Cancer Prostatic Dis., 2016, 19(4), 358-366.
[http://dx.doi.org/10.1038/pcan.2016.29] [PMID: 27431500]
[43]
Kang, S.W.; Lee, S.; Lee, E.K. ROS and energy metabolism in cancer cells: Alliance for fast growth. Arch. Pharm. Res., 2015, 38(3), 338-345.
[http://dx.doi.org/10.1007/s12272-015-0550-6] [PMID: 25599615]
[44]
Al-Oqail, M.M. Anticancer efficacies of Krameria lappacea extracts against human breast cancer cell line (MCF-7): Role of oxidative stress and ROS generation. Saudi Pharm. J., 2021, 29(3), 244-251.
[http://dx.doi.org/10.1016/j.jsps.2021.01.008] [PMID: 33981173]
[45]
Qiao, L.; Liu, J.; Kuang, S.; Liao, X.; Kou, J.; Ji, L.; Chao, H. A mitochondrion-targeted BODIPY-Ir(III) conjugate as a photoinduced ROS generator for the oxidative destruction of triple-negative breast cancer cells. Dalton Trans., 2021, 50(40), 14332-14341.
[http://dx.doi.org/10.1039/D1DT01460A] [PMID: 34558567]
[46]
Ulker, O.C.; Panieri, E.; Suzen, S.; Jaganjac, M.; Zarkovic, N.; Saso, L. Short overview on the relevance of microRNA-reactive oxygen species (ROS) interactions and lipid peroxidation for modulation of oxidative stress-mediated signalling pathways in cancer treatment. J. Pharm. Pharmacol., 2022, 74(4), 503-515.
[PMID: 33769543]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy