Generic placeholder image

Current Pharmaceutical Design

Author(s): Kai Zhao*, Yun Cai, Faisal Raza, Hajra Zafar, Liang Pan, Xifeng Zheng, Wenjie Xu, Ran Li, Feng Shi* and Yongbin Ma*

DOI: 10.2174/0113816128306477240625101849

DownloadDownload PDF Flyer Cite As
Matrine-loaded Nano-liposome Induces Apoptosis in Human Esophageal-squamous Carcinoma KYSE-150 Cells

Page: [2303 - 2312] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Introduction: Esophageal-Squamous Cell Carcinoma (ESCC) is often diagnosed at the middle or late stage, thus requiring more effective therapeutic strategies. Pharmacologically, the anti-tumor activity of the principal active constituent of Sophora flavescens, matrine (MA), has been explored widely. Notwithstanding, it is significant to nanotechnologically enhance the anti-tumor activity of MA in view of its potential to distribute non-tumor cells.

Methods: Herein, MA-loaded Nano-Liposomes (MNLs) were prepared to enhance the effect of anti-ESCC. The MNL showed a smaller sized particle (25.95 ± 1.02 nm) with a low polydispersed index (PDI = 0.130 ± 0.054), uniform spherical morphology, good solution stability, and encapsulated efficiency (65.55% ± 2.47). Furthermore, we determined the characteristics of KYSE-150 cells by cell viability assay, IC50, Mitochondrial Membrane Potential (MMP), Western blot, and apoptotic analysis, which indicated that MNLs down-regulated the cell viability and IC50 in a concentration-dependent manner and induced a significant change in JC-1 fluorescence from red to green.

Results: The above observations resulted in increased Bax and Caspase-3 levels, coupled with a substantial decrease in Bcl-2 and apoptotic promotion at the advanced stage compared with MA.

Conclusion: Based on these results, MNLs may serve as a more effective and promising therapeutic option for ESCC.

[1]
Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet 2013; 381(9864): 400-12.
[http://dx.doi.org/10.1016/S0140-6736(12)60643-6] [PMID: 23374478]
[2]
Watanabe M, Otake R, Kozuki R, et al. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg Today 2020; 50(1): 12-20.
[http://dx.doi.org/10.1007/s00595-019-01878-7] [PMID: 31535225]
[3]
Abnet CC, Arnold M, Wei WQ. Epidemiology of Esophageal squamous cell carcinoma. Gastroenterology 2018; 154(2): 360-73.
[http://dx.doi.org/10.1053/j.gastro.2017.08.023] [PMID: 28823862]
[4]
Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin 2019; 69(5): 363-85.
[http://dx.doi.org/10.3322/caac.21565] [PMID: 31184787]
[5]
Cao L, Wang X, Zhu G, et al. Traditional Chinese medicine therapy for esophageal cancer: A literature review. Integr Cancer Ther 2021; 20: 15347354211061720.
[http://dx.doi.org/10.1177/15347354211061720] [PMID: 34825600]
[6]
Hu C, Zhang X, Wei W, et al. Matrine attenuates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via maintaining AMPKα/UCP2 pathway. Acta Pharm Sin B 2019; 9(4): 690-701.
[http://dx.doi.org/10.1016/j.apsb.2019.03.003] [PMID: 31384530]
[7]
Zhaowu Z, Xiaoli W, Yangde Z, Nianfeng L. Preparation of matrine ethosome, its percutaneous permeation in vitro and anti-inflammatory activity in vivo in rats. J Liposome Res 2009; 19(2): 155-62.
[http://dx.doi.org/10.1080/08982100902722381] [PMID: 19241204]
[8]
Ma W, Xu J, Zhang Y, et al. Matrine pre-treatment suppresses AGEs- induced HCSMCs fibrotic responses by regulating Poldip2/mTOR pathway. Eur J Pharmacol 2019; 865: 172746.
[http://dx.doi.org/10.1016/j.ejphar.2019.172746] [PMID: 31634459]
[9]
Wang W, You R, Qin W, et al. Anti-tumor activities of active ingredients in compound kushen injection. Acta Pharmacol Sin 2015; 36(6): 676-9.
[http://dx.doi.org/10.1038/aps.2015.24] [PMID: 25982630]
[10]
Chi G, Xu D, Zhang B, Yang F. Matrine induces apoptosis and autophagy of glioma cell line U251 by regulation of circRNA-104075/BCL-9. Chem Biol Interact 2019; 308: 198-205.
[http://dx.doi.org/10.1016/j.cbi.2019.05.030] [PMID: 31112718]
[11]
Wang M, Liu G, Li H. Extraction of matrine from Sophora flavescens Ait. and evaluation of its inhibitory effects on human nasopharyngeal carcinoma CNE-2 cells. Food Sci Technol 2018; 38 (Suppl. 1): 333-7.
[http://dx.doi.org/10.1590/fst.24117]
[12]
Zhou Y, Feng J, You L, Meng H, Qian W. Matrine and CYC116 synergistically inhibit growth and induce apoptosis in multiple myeloma cells. Chin J Integr Med 2015; 21(8): 635-9.
[http://dx.doi.org/10.1007/s11655-015-1975-y] [PMID: 25804197]
[13]
Zhang JQ, Li YM, Liu T, et al. Antitumor effect of matrine in human hepatoma G2 cells by inducing apoptosis and autophagy. World J Gastroenterol 2010; 16(34): 4281-90.
[http://dx.doi.org/10.3748/wjg.v16.i34.4281] [PMID: 20818811]
[14]
Yang A, Zhu J, Xu F, et al. Anticancer effect of a combination of cisplatin and matrine on cervical cancer U14 cells and U14 tumor-bearing mice, and possible mechanism of action involved. Trop J Pharm Res 2022; 20(8): 1631-8.
[http://dx.doi.org/10.4314/tjpr.v20i8.12]
[15]
Jin H, Sun Y, Wang S, Cheng X. Matrine activates PTEN to induce growth inhibition and apoptosis in V600EBRAF harboring melanoma cells. Int J Mol Sci 2013; 14(8): 16040-57.
[http://dx.doi.org/10.3390/ijms140816040] [PMID: 23912239]
[16]
Zhang S, Cheng B, Li H, et al. Matrine inhibits proliferation and induces apoptosis of human colon cancer LoVo cells by inactivating Akt pathway. Mol Biol Rep 2014; 41(4): 2101-8.
[http://dx.doi.org/10.1007/s11033-014-3059-z] [PMID: 24452711]
[17]
Li Y, Lin H, Deng N, Xie L, Luo R. Matrine from Vietnamese sophora root inhibits the growth of oral squamous cell carcinoma cells in vitro and in vivo. Food Sci Technol 2019; 39(4): 855-8.
[http://dx.doi.org/10.1590/fst.11518]
[18]
Gu J, Wang X, Zhang L, et al. Matrine suppresses cell growth of diffuse large B-cell lymphoma via inhibiting CaMKIIγ/c-Myc/CDK6 signaling pathway. BMC Complement Med Ther 2021; 21(1): 163.
[http://dx.doi.org/10.1186/s12906-021-03315-0] [PMID: 34088288]
[19]
Shao H, Yang B, Hu R, Wang Y. Matrine effectively inhibits the proliferation of breast cancer cells through a mechanism related to the NF-κB signaling pathway. Oncol Lett 2013; 6(2): 517-20.
[http://dx.doi.org/10.3892/ol.2013.1399] [PMID: 24137358]
[20]
Luo C, Zhu Y, Jiang T, et al. Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family. Toxicology 2007; 229(3): 245-52.
[http://dx.doi.org/10.1016/j.tox.2006.10.020] [PMID: 17134813]
[21]
Jiang JH, Pi J, Jin H, Yang F, Cai JY. Chinese herb medicine matrine induce apoptosis in human esophageal squamous cancer KYSE-150 cells through increasing reactive oxygen species and inhibiting mitochondrial function. Pathol Res Pract 2018; 214(5): 691-9.
[http://dx.doi.org/10.1016/j.prp.2018.03.015] [PMID: 29567333]
[22]
Gabizon AA, Shmeeda H, Zalipsky S. Pros and cons of the liposome platform in cancer drug targeting. J Liposome Res 2006; 16(3): 175-83.
[http://dx.doi.org/10.1080/08982100600848769] [PMID: 16952872]
[23]
Nikpoor AR, Tavakkol-Afshari J, Gholizadeh Z, et al. Nanoliposome-mediated targeting of antibodies to tumors: IVIG antibodies as a model. Int J Pharm 2015; 495(1): 162-70.
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.048] [PMID: 26302860]
[24]
Funaya N, Haginaka J. Matrine and oxymatrine-imprinted monodisperse polymers prepared by precipitation polymerization and their applications for the selective extraction of matrine-type alkaloids from Sophora flavescens Aiton. J Chromatogr A 2012; 1248: 18-23.
[http://dx.doi.org/10.1016/j.chroma.2012.05.081] [PMID: 22695694]
[25]
Wu G, Zhou W, Zhao J, et al. Matrine alleviates lipopolysaccharide-induced intestinal inflammation and oxidative stress via CCR7 signal. Oncotarget 2017; 8(7): 11621-8.
[http://dx.doi.org/10.18632/oncotarget.14598] [PMID: 28086227]
[26]
You L, Yang C, Du Y, et al. A systematic review of the pharmacology, toxicology and pharmacokinetics of matrine. Front Pharmacol 2020; 11: 01067.
[http://dx.doi.org/10.3389/fphar.2020.01067] [PMID: 33041782]
[27]
Liang CZ, Zhang JK, Shi Z, Liu B, Shen CQ, Tao HM. Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro and in vivo through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2. Cancer Chemother Pharmacol 2012; 69(2): 317-31.
[http://dx.doi.org/10.1007/s00280-011-1699-4] [PMID: 21717192]
[28]
Niu H, Zhang Y, Wu B, Zhang Y, Jiang H, He P. Matrine induces the apoptosis of lung cancer cells through downregulation of inhibitor of apoptosis proteins and the Akt signaling pathway. Oncol Rep 2014; 32(3): 1087-93.
[http://dx.doi.org/10.3892/or.2014.3273] [PMID: 24969052]
[29]
Li H, Li X, Bai M, Suo Y, Zhang G, Cao X. Matrine inhibited proliferation and increased apoptosis in human breast cancer MCF-7 cells via upregulation of Bax and downregulation of Bcl-2. Int J Clin Exp Pathol 2015; 8(11): 14793-9.
[PMID: 26823806]
[30]
Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J Control Release 2000; 65(1-2): 271-84.
[http://dx.doi.org/10.1016/S0168-3659(99)00248-5] [PMID: 10699287]
[31]
Sawant RR, Torchilin VP. Challenges in development of targeted liposomal therapeutics. AAPS J 2012; 14(2): 303-15.
[http://dx.doi.org/10.1208/s12248-012-9330-0] [PMID: 22415612]
[32]
Wang D, Veena MS, Stevenson K, et al. Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibition of nuclear factor kappaB by an AKT-independent pathway. Clin Cancer Res 2008; 14(19): 6228-36.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5177] [PMID: 18829502]
[33]
Jung H, Bae J, Ko SK, Sohn UD. Ultrasonication processed Panax ginseng berry extract induces apoptosis through an intrinsic apoptosis pathway in HepG2 cells. Arch Pharm Res 2016; 39(6): 855-62.
[http://dx.doi.org/10.1007/s12272-016-0760-6] [PMID: 27233905]
[34]
Wasim L, Chopra M. Synergistic anticancer effect of panobinostat and topoisomerase inhibitors through ROS generation and intrinsic apoptotic pathway induction in cervical cancer cells. Cell Oncol 2018; 41(2): 201-12.
[http://dx.doi.org/10.1007/s13402-017-0366-0] [PMID: 29260509]
[35]
Ma ZJ, Lu L, Yang JJ, et al. Lariciresinol induces apoptosis in HepG2 cells via mitochondrial-mediated apoptosis pathway. Eur J Pharmacol 2018; 821: 1-10.
[http://dx.doi.org/10.1016/j.ejphar.2017.12.027] [PMID: 29247613]