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Anti-Cancer Agents in Medicinal Chemistry

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

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Research Article

Anti-Tumor and Anti-Metastasis Effects of Berbamine-Loaded Lipid Nanoparticles on Pancreatic Cancer

Author(s): Zhiyi Tang, Yichun Niu, Zhiyuan Xu, Yanmei Shi, Yaqiong Liu, Wen Fu, Mengyao Zheng, Haiyu He* and Tao Wu*

Volume 22, Issue 18, 2022

Published on: 18 July, 2022

Page: [3097 - 3106] Pages: 10

DOI: 10.2174/1871520622666220501161636

Price: $65

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Abstract

Objective: The aim of the study was to investigate the therapeutic potential of Berbamine-loaded lipid nanoparticles (BBM-NPs) in pancreatic cancer.

Methods: Dopamine polymerization-polylactide-TPGS nanoparticles were synthesized to prepare BBM-NPs, and the change in particle size of BBM-NPs was measured. Cell Counting Kit-8 (CCK8) assay, plate cloning experiment, and apoptosis analysis were performed to evaluate the cytotoxicity of BBM-NPs against the pancreatic cancer cells (PANC-1 and AsPC-1). Migration and invasion abilities of the tumor cells were determined by Transwell and wound healing assays. The intracellular level of ROS and expression of tumor progression-related proteins were measured using ROS-kit and western blot assay. Besides, an in vivo study was performed in the Balb/c nude mice to analyze the function of BBM-NPs in tumor growth.

Results: The in vitro studies showed that BBM-NPs with stable particle size and sustained drug release effectively inhibited the viability, proliferation, migration, and invasion of pancreatic cancer cells, while promoting cell apoptosis. Moreover, the in vivo experiments revealed that compared to Free BBM, BBM-NPs exhibited a stronger inhibitory effect on the growth of xenograft tumors derived from PANC-1 cells in mice. In addition, increased expressions of ROS, Bax, Cleaved Caspase-3, and γ-H2AX, as well as decreased expressions of MMP2, MMP9 and Bcl-2 were identified in both Free BBM and BBM-NPs groups, while BBM-NPs exhibited a stronger effect on protein expression than Free BBM.

Conclusion: In summary, BBM-loaded lipid nanoparticles enhanced the therapeutic effects of BBM on pancreatic cancer, providing a promising strategy for targeted cancer therapy.

Keywords: Berbamine, berbamine-loaded lipid nanoparticles, pancreatic cancer, anti-metastasis, anti-tumor, tumor progression related proteins.

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[1]
The Lancet Gastroenterology Hepatology. Pancreatic cancer: A state of emergency? Lancet Gastroenterol. Hepatol., 2021, 6(2), 81.
[http://dx.doi.org/10.1016/S2468-1253(20)30397-6] [PMID: 33444531]
[2]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN Esti-mates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Tempero, M.A. NCCN guidelines updates: Pancreatic cancer. J Natl Compr Canc Netw, 2019, 17(5.5), 603-605.
[4]
Hu, C.; Hart, S.N.; Polley, E.C.; Gnanaolivu, R.; Shimelis, H.; Lee, K.Y.; Lilyquist, J.; Na, J.; Moore, R.; Antwi, S.O.; Bamlet, W.R.; Chaffee, K.G.; DiCarlo, J.; Wu, Z.; Samara, R.; Kasi, P.M.; McWilliams, R.R.; Petersen, G.M.; Couch, F.J. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA, 2018, 319(23), 2401-2409.
[http://dx.doi.org/10.1001/jama.2018.6228] [PMID: 29922827]
[5]
Zeng, S.; Pöttler, M.; Lan, B.; Grützmann, R.; Pilarsky, C.; Yang, H. Chemoresistance in pancreatic cancer. Int. J. Mol. Sci., 2019, 20(18), 4504.
[http://dx.doi.org/10.3390/ijms20184504] [PMID: 31514451]
[6]
Tuorkey, M.J. Cancer therapy with phytochemicals: Present and future perspectives. Biomed. Environ. Sci., 2015, 28(11), 808-819.
[http://dx.doi.org/10.1016/S0895-3988(15)30111-2] [PMID: 26695359]
[7]
Hou, Z.B.; Lu, K.J.; Wu, X.L.; Chen, C.; Huang, X.E.; Yin, H.T. In vitro and in vivo antitumor evaluation of berbamine for lung cancer treatment. Asian Pac. J. Cancer Prev., 2014, 15(4), 1767-1769.
[http://dx.doi.org/10.7314/APJCP.2014.15.4.1767] [PMID: 24641406]
[8]
Zhang, H.; Jiao, Y.; Shi, C.; Song, X.; Chang, Y.; Ren, Y.; Shi, X. Berbamine suppresses cell proliferation and promotes apoptosis in ovar-ian cancer partially via the inhibition of Wnt/β-catenin signaling. Acta Biochim. Biophys. Sin. (Shanghai), 2018, 50(6), 532-539.
[http://dx.doi.org/10.1093/abbs/gmy036] [PMID: 29701777]
[9]
Han, C.; Wang, Z.; Chen, S.; Li, L.; Xu, Y.; Kang, W.; Wei, C.; Ma, H.; Wang, M.; Jin, X. Berbamine suppresses the progression of bladder cancer by modulating the ROS/NF-κB axis. Oxid. Med. Cell. Longev., 2021, 2021, 8851763.
[http://dx.doi.org/10.1155/2021/8851763] [PMID: 33520087]
[10]
Jin, X.; Wu, Y. Berbamine enhances the antineoplastic activity of gemcitabine in pancreatic cancer cells by activating transforming growth factor-β/Smad signaling. Anat. Rec. (Hoboken), 2014, 297(5), 802-809.
[http://dx.doi.org/10.1002/ar.22897] [PMID: 24619961]
[11]
Hu, B.; Cai, H.; Yang, S.; Tu, J.; Huang, X.; Chen, G. Berbamine enhances the efficacy of gefitinib by suppressing STAT3 signaling in pancreatic cancer cells. OncoTargets Ther., 2019, 12, 11437-11451.
[http://dx.doi.org/10.2147/OTT.S223242] [PMID: 31920333]
[12]
Löhr, M.; van der Wijngaart, W.; Fagerberg, B. Nanoparticles for cancer therapy. Lakartidningen, 2017, 114. EIAC.
[13]
Chaturvedi, V.K.; Singh, A.; Singh, V.K.; Singh, M.P. Cancer nanotechnology: A new revolution for cancer diagnosis and therapy. Curr. Drug Metab., 2019, 20(6), 416-429.
[http://dx.doi.org/10.2174/1389200219666180918111528] [PMID: 30227814]
[14]
Wang-Gillam, A.; Li, C-P.; Bodoky, G.; Dean, A.; Shan, Y-S.; Jameson, G.; Macarulla, T.; Lee, K-H.; Cunningham, D.; Blanc, J.F.; Hubner, R.A.; Chiu, C-F.; Schwartsmann, G.; Siveke, J.T.; Braiteh, F.; Moyo, V.; Belanger, B.; Dhindsa, N.; Bayever, E.; Von Hoff, D.D.; Chen, L-T.; Adoo, C.; Anderson, T.; Asselah, J.; Azambuja, A.; Bampton, C.; Barrios, C.H.; Bekaii-Saab, T.; Bohuslav, M.; Chang, D.; Chen, J-S.; Chen, Y-C.; Choi, H.J.; Chung, I.J.; Chung, V.; Csoszi, T.; Cubillo, A.; DeMarco, L.; de Wit, M.; Dragovich, T.; Edenfield, W.; Fein, L.E.; Franke, F.; Fuchs, M.; Gonzales-Cruz, V.; Gozza, A.; Fernando, R.H.; Iaffaioli, R.; Jakesova, J.; Kahan, Z.; Karimi, M.; Kim, J.S.; Korben-feld, E.; Lang, I.; Lee, F-C.; Lee, K-D.; Lipton, L.; Ma, W.W.; Mangel, L.; Mena, R.; Palmer, D.; Pant, S.; Park, J.O.; Piacentini, P.; Pelzer, U.; Plazas, J.G.; Prasad, C.; Rau, K-M.; Raoul, J-L.; Richards, D.; Ross, P.; Schlittler, L.; Smakal, M.; Stahalova, V.; Sternberg, C.; Seuffer-lein, T.; Tebbutt, N.; Vinholes, J.J.; Wadlow, R.; Wenczl, M.; Wong, M. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): A global, randomised, open-label, phase 3 trial. Lancet, 2016, 387(10018), 545-557.
[http://dx.doi.org/10.1016/S0140-6736(15)00986-1] [PMID: 26615328]
[15]
Parhi, P.; Suklabaidya, S.; Kumar Sahoo, S. Enhanced anti-metastatic and anti-tumorigenic efficacy of Berbamine loaded lipid nanoparti-cles in vivo. Sci. Rep., 2017, 7(1), 5806.
[http://dx.doi.org/10.1038/s41598-017-05296-y] [PMID: 28724926]
[16]
Jiang, Z.M.; Dai, S.P.; Xu, Y.Q.; Li, T.; Xie, J.; Li, C.; Zhang, Z.H. Crizotinib-loaded polymeric nanoparticles in lung cancer chemotherapy. Med. Oncol., 2015, 32(7), 193.
[http://dx.doi.org/10.1007/s12032-015-0636-5] [PMID: 26025486]
[17]
Wang, Y.R.; Yang, S.Y.; Chen, G.X.; Wei, P. Barbaloin loaded polydopamine-polylactide-TPGS (PLA-TPGS) nanoparticles against gastric cancer as a targeted drug delivery system: Studies in vitro and in vivo. Biochem. Biophys. Res. Commun., 2018, 499(1), 8-16.
[http://dx.doi.org/10.1016/j.bbrc.2018.03.069] [PMID: 29534962]
[18]
Mizrahi, J.D.; Surana, R.; Valle, J.W.; Shroff, R.T. Pancreatic cancer. Lancet, 2020, 395(10242), 2008-2020.
[http://dx.doi.org/10.1016/S0140-6736(20)30974-0] [PMID: 32593337]
[19]
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, 5517143.
[http://dx.doi.org/10.1155/2021/5517143] [PMID: 34306137]
[20]
Liu, L.; Yan, J.; Cao, Y.; Yan, Y.; Shen, X.; Yu, B.; Tao, L.; Wang, S. Proliferation, migration and invasion of triple negative breast cancer cells are suppressed by berbamine via the PI3K/Akt/MDM2/p53 and PI3K/Akt/mTOR signaling pathways. Oncol. Lett., 2021, 21(1), 70.
[http://dx.doi.org/10.3892/ol.2020.12331] [PMID: 33365081]
[21]
Alavi, M.; Hamidi, M. Passive and active targeting in cancer therapy by liposomes and lipid nanoparticles. Drug Metab. Pers. Ther., 2019, 34(1)
[http://dx.doi.org/10.1515/dmpt-2018-0032] [PMID: 30707682]
[22]
Javed Iqbal, M.; Quispe, C.; Javed, Z.; Sadia, H.; Qadri, Q.R.; Raza, S.; Salehi, B.; Cruz-Martins, N.; Abdulwanis Mohamed, Z.; Sani Jaafaru, M.; Abdull Razis, A.F.; Sharifi-Rad, J. Nanotechnology-based strategies for berberine delivery system in cancer treatment: Pulling strings to keep berberine in power. Front. Mol. Biosci., 2021, 7, 624494.
[http://dx.doi.org/10.3389/fmolb.2020.624494] [PMID: 33521059]
[23]
Li, G.; Zhao, M.; Xu, F.; Yang, B.; Li, X.; Meng, X.; Teng, L.; Sun, F.; Li, Y. Synthesis and biological application of polylactic acid. Molecules, 2020, 25(21), E5023.
[http://dx.doi.org/10.3390/molecules25215023] [PMID: 33138232]
[24]
Yang, C.; Wu, T.; Qi, Y.; Zhang, Z. Recent advances in the application of vitamin E TPGS for drug delivery. Theranostics, 2018, 8(2), 464-485.
[http://dx.doi.org/10.7150/thno.22711] [PMID: 29290821]
[25]
Zhu, D.; Tao, W.; Zhang, H.; Liu, G.; Wang, T.; Zhang, L.; Zeng, X.; Mei, L. Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Acta Biomater., 2016, 30, 144-154.
[http://dx.doi.org/10.1016/j.actbio.2015.11.031] [PMID: 26602819]
[26]
Kalyane, D.; Raval, N.; Maheshwari, R.; Tambe, V.; Kalia, K.; Tekade, R.K. Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Mater. Sci. Eng. C, 2019, 98, 1252-1276.
[http://dx.doi.org/10.1016/j.msec.2019.01.066] [PMID: 30813007]
[27]
Edlich, F. BCL-2 proteins and apoptosis: Recent insights and unknowns. Biochem. Biophys. Res. Commun., 2018, 500(1), 26-34.
[http://dx.doi.org/10.1016/j.bbrc.2017.06.190] [PMID: 28676391]
[28]
Moloney, J.N.; Cotter, T.G. ROS signalling in the biology of cancer. Semin. Cell Dev. Biol., 2018, 80, 50-64.
[http://dx.doi.org/10.1016/j.semcdb.2017.05.023] [PMID: 28587975]
[29]
Srinivas, U.S.; Tan, B.W.Q.; Vellayappan, B.A.; Jeyasekharan, A.D. ROS and the DNA damage response in cancer. Redox Biol., 2019, 25, 101084.
[http://dx.doi.org/10.1016/j.redox.2018.101084] [PMID: 30612957]
[30]
Kuo, L.J.; Yang, L.X. Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo, 2008, 22(3), 305-309.
[PMID: 18610740]

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