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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Aloperine Prevents Migration, Invasion, and Adhesion by Upregulating TIMP-4 in Human Bladder Cancer Cells

Author(s): Mingning Qiu, Liming Yu, Jinglan Liang, Juan Xia, Xuguang Wang* and Jie Liu*

Volume 30, Issue 3, 2023

Published on: 03 February, 2023

Page: [250 - 259] Pages: 10

DOI: 10.2174/0929866530666230124112754

Price: $65

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Abstract

Background: Aloperine (ALO) is an important active component of quinolizidine alkaloids in Sophora flavescens A and Sophora alopecuroides L, and has effective anticancer activity against multiple cancers. However, the influence and mechanism of ALO on migration, invasion, and adhesion in bladder cancer cells remain unclear.

Objective: The aim of this study is to determine the anticancer effect of ALO on migration, invasion, and adhesion in bladder cancer cells and to investigate its potential TIMP-4-related mechanism.

Methods: Cell viability, cytotoxicity, wound healing, Transwell invasion, cell adhesion, real-time qPCR, western blot, and ELISA assays were performed to analyze the effect of ALO on migration, invasion, and adhesion in bladder cancer 5637 and UM-UC-3 cells. Furthermore, the anti-TIMP-4 antibody was used to explore the potential effect on ALO-inhibited bladder cancer cells.

Results: We have found that ALO significantly suppressed migration, invasion, and adhesion in bladder cancer cells. Furthermore, ALO could downregulate the expression of MMP-2 and MMP-9 mRNAs and proteins, and increase the expression of TIMP-4 mRNA and protein. Moreover, the anti- TIMP-4 antibody reversed the prevention of migration, invasion, and adhesion in ALO-treated bladder cancer cells.

Conclusion: The data in this study suggest that ALO suppressed migration, invasion, and adhesion in bladder cancer cells by upregulating the expression of TIMP-4.

Keywords: Migration, invasion, adhesion, TIMP-4, aloperine, bladder cancer cells.

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[1]
He, X.; Fang, J.; Huang, L.; Wang, J.; Huang, X. Sophora flave-scens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine. J. Ethnopharmacol., 2015, 172, 10-29.
[http://dx.doi.org/10.1016/j.jep.2015.06.010] [PMID: 26087234]
[2]
Wang, R.; Deng, X.; Gao, Q.; Wu, X.; Han, L.; Gao, X.; Zhao, S.; Chen, W.; Zhou, R.; Li, Z.; Bai, C. Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review. J. Ethnopharmacol., 2020, 248, 112172.
[http://dx.doi.org/10.1016/j.jep.2019.112172] [PMID: 31442619]
[3]
Han, W.; Kong, D.; Lu, Q.; Zhang, W.; Fan, Z. Aloperine inhibits proliferation and promotes apoptosis in colorectal cancer cells by regulating the circNSUN2/miR-296-5p/STAT3 pathway. Drug Des. Devel. Ther., 2021, 15, 857-870.
[http://dx.doi.org/10.2147/DDDT.S288473] [PMID: 33664565]
[4]
Han, W.; Kong, D.; Lu, Q.; Zhang, W.; Fan, Z. Aloperine inhibits colorectal cancer cell proliferation and metastasis progress via regulating miR-296-5p/STAT3 axis. Tissue Cell, 2022, 74, 101706.
[http://dx.doi.org/10.1016/j.tice.2021.101706] [PMID: 34883316]
[5]
Chen, Y.D.; Cai, F.Y.; Mao, Y.Z.; Yang, Y.S.; Xu, K.; Liu, X.F.; Fan, W.W.; Chen, W.; Jiang, F.Q.; Zhang, H. The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop. Chin. J. Nat. Med., 2021, 19(11), 815-824.
[http://dx.doi.org/10.1016/S1875-5364(21)60106-1] [PMID: 34844720]
[6]
Qiu, M.; Liu, J.; Su, Y.; Liu, J.; Wu, C.; Zhao, B. Aloperine induces apoptosis by a reactive oxygen species activation mechanism in human ovarian cancer cells. Protein Pept. Lett., 2020, 27(9), 860-869.
[http://dx.doi.org/10.2174/0929866527666200320094313] [PMID: 32196436]
[7]
Zhang, L.; Liang, J.; Liu, X.; Wu, J.; Tan, D.; Hu, W. Aloperine exerts antitumor effects on bladder cancer in vitro. OncoTargets Ther., 2020, 13, 10351-10360.
[http://dx.doi.org/10.2147/OTT.S260215] [PMID: 33116615]
[8]
Ozdemir, K.; Zengin, I.; Guney Eskiler, G.; Kocer, H.B.; Ozkan, A.D.; Demiray, T.; Sahin, E.O. The predictive role of MMP-2, MMP-9, TIMP-1 and TIMP-2 serum levels in the complete response of the tumor to chemotherapy in breast cancer patients. J. Invest. Surg., 2022, 35(7), 1544-1550.
[http://dx.doi.org/10.1080/08941939.2022.2080308] [PMID: 35636767]
[9]
Eckfeld, C.; Haussler, D.; Schoeps, B.; Hermann, C.D.; Kruger, A. Functional disparities within the TIMP family in cancer: Hints from molecular divergence. Cancer Metastasis Rev., 2019, 38(3), 469-481.
[http://dx.doi.org/10.1007/s10555-019-09812-6] [PMID: 31529339]
[10]
Tian, D.; Li, Y.; Li, X.; Tian, Z. Aloperine inhibits proliferation, migration and invasion and induces apoptosis by blocking the Ras signaling pathway in human breast cancer cells. Mol. Med. Rep., 2018, 18(4), 3699-3710.
[http://dx.doi.org/10.3892/mmr.2018.9419] [PMID: 30132540]
[11]
Qiu, M.; Chen, L.; Tan, G.; Ke, L.; Zhang, S.; Chen, H.; Liu, J. A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells. Sci. Rep., 2015, 5(1), 15104.
[http://dx.doi.org/10.1038/srep15104] [PMID: 26458509]
[12]
Liu, J.; Wen, X.; Liu, B.; Zhang, Q.; Zhang, J.; Miao, H.; Zhu, R. Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP-2 and MMP-9. Mol. Med. Rep., 2016, 13(3), 2401-2408.
[http://dx.doi.org/10.3892/mmr.2016.4872] [PMID: 26847170]
[13]
Li, J.; Qiu, M.; Chen, L.; Liu, L.; Tan, G.; Liu, J. Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism. Oncol. Lett., 2017, 13(2), 613-620.
[http://dx.doi.org/10.3892/ol.2016.5519] [PMID: 28356937]
[14]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin., 2022, 72(1), 7-33.
[http://dx.doi.org/10.3322/caac.21708] [PMID: 35020204]
[15]
Miller, K.D.; Nogueira, L.; Devasia, T.; Mariotto, A.B.; Yabroff, K.R.; Jemal, A.; Kramer, J.; Siegel, R.L. Cancer treatment and survivorship statistics, 2022. CA Cancer J. Clin., 2022, 72(5), 409-436.
[http://dx.doi.org/10.3322/caac.21731] [PMID: 35736631]
[16]
Xia, C.; Dong, X.; Li, H.; Cao, M.; Sun, D.; He, S.; Yang, F.; Yan, X.; Zhang, S.; Li, N.; Chen, W. Cancer statistics in China and United States, 2022: Profiles, trends, and determinants. Chin. Med. J. , 2022, 135(5), 584-590.
[http://dx.doi.org/10.1097/CM9.0000000000002108] [PMID: 35143424]
[17]
Li, Y.; Wang, G.; Liu, J.; Ouyang, L. Quinolizidine alkaloids derivatives from Sophora alopecuroides linn: Bioactivities, structure-activity relationships and preliminary molecular mechanisms. Eur. J. Med. Chem., 2020, 188, 111972.
[http://dx.doi.org/10.1016/j.ejmech.2019.111972] [PMID: 31884408]
[18]
Augusciak-Duma, A.; Stepien, K.L.; Lesiak, M.; Gutmajster, E.; Fus-Kujawa, A.; Botor, M.; Sieron, A.L. Expression gradient of metalloproteinases and their inhibitors from proximal to distal segments of abdominal aortic aneurysm. J. Appl. Genet., 2021, 62(3), 499-506.
[http://dx.doi.org/10.1007/s13353-021-00642-3] [PMID: 34091862]
[19]
Huang, C.; Xu, S.; Luo, Z.; Li, D.; Wang, R.; Wang, T. Epidemiological evidence between variants in matrix metalloproteinases-2, -7, and -9 and cancer risk. Front. Oncol., 2022, 12, 856831.
[http://dx.doi.org/10.3389/fonc.2022.856831] [PMID: 35574300]
[20]
Fouad, H.; Salem, H.; Ellakwa, D.E.S.; Abdel-Hamid, M. MMP-2 and MMP-9 as prognostic markers for the early detection of urinary bladder cancer. J. Biochem. Mol. Toxicol., 2019, 33(4), e22275.
[http://dx.doi.org/10.1002/jbt.22275] [PMID: 30548095]
[21]
Escalona, R.M.; Kannourakis, G.; Findlay, J.K.; Ahmed, N. Expression of TIMPs and MMPs in ovarian tumors, ascites, ascites-derived cells, and cancer cell lines: Characteristic modulatory response before and after chemotherapy treatment. Front. Oncol., 2022, 11, 796588.
[http://dx.doi.org/10.3389/fonc.2021.796588] [PMID: 35047406]
[22]
Lu, S.; Xiao, X.; Cheng, M. Matrine inhibits IL-1β-induced expression of matrix metalloproteinases by suppressing the activation of MAPK and NF-κB in human chondrocytes in vitro. Int. J. Clin. Exp. Pathol., 2015, 8(5), 4764-4772.
[PMID: 26191166]
[23]
Zhang, S.; Kan, Q.C.; Xu, Y.; Zhang, G.X.; Zhu, L. Inhibitory effect of matrine on blood-brain barrier disruption for the treatment of experimental autoimmune encephalomyelitis. Mediators Inflamm., 2013, 2013, 736085.
[http://dx.doi.org/10.1155/2013/736085] [PMID: 24194630]
[24]
Lizarraga, F.; Espinosa, M.; Ceballos-Cancino, G.; Vazquez-Santillan, K.; Bahena-Ocampo, I.; Schwarz-Cruz y Celis, A.; Vega-Gordillo, M.; Garcia Lopez, P.; Maldonado, V.; Melendez-Zajgla, J. Tissue inhibitor of metalloproteinases-4 (TIMP-4) regulates stemness in cervical cancer cells. Mol. Carcinog., 2016, 55(12), 1952-1961.
[http://dx.doi.org/10.1002/mc.22442] [PMID: 26618609]

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