Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

The Effect of Beta-lactoglobulin Nanocapsules Containing Astaxanthin and 5-fluorouracil on the Antioxidant Enzymes Activity of Superoxide Dismutase, Catalase and Glutathione Peroxidase in HCT116 Colorectal Cancer Cell Line

Author(s): Hamid Gholami, Roghayeh Abbasalipourkabir, Nasrin Ziamajidi, Adeleh Divsalar, Maryam Saeidifar and Sadegh Zarei*

Volume 18, Issue 5, 2023

Published on: 28 April, 2023

Page: [407 - 414] Pages: 8

DOI: 10.2174/1574885518666230403111101

Price: $65

Abstract

Background: The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anticancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and antiapoptotic properties used to prevent and treat some cancers.

Objectives: In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined.

Methods: In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group in which HCT116 cells were not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT, and GPX was measured by a colorimetric method in HCT116 cells.

Results: Different treatments reduced the cell viability and increased apoptotic cells in a timedependent manner, which was significant for beta-lactoglobulin nanocapsules treatment (P <0.05). It means receiving more 5-FU or ATX in the encapsulated form by HCT116 cells. The antioxidant enzyme activity of SOD, CAT, and GPX in HCT116 cells treated with beta-lactoglobulin nanocapsule treatment significantly increased compared to the control group (P <0.001). Moreover, the antioxidant activity of these enzymes in different treatments containing ATX (free or encapsulation) was significantly higher than in other treatments (P <0.05). The most increase in the activity of antioxidant enzymes is recorded in the treatment of nanocapsules containing ATX and 5-FU simultaneously.

Conclusion: Increased activity of antioxidant enzymes in addition to the induction of apoptosis in colorectal cancer cells by various treatments of beta-lactoglobulin nanocapsules indicates more effective drug administration in encapsulated form as well as synergistic thera[peutic effects of ATX and 5-FU. Moreover, the main increase in antioxidant enzyme activity may be related to ATX.

Graphical Abstract

[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Curado M-P, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M. Cancer incidence in five continents. IARC Press, International Agency for Research on Cancer 2007; IX..
[3]
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66(4): 683-91.
[http://dx.doi.org/10.1136/gutjnl-2015-310912] [PMID: 26818619]
[4]
Ganji A, Safavi M, Nouraie S, et al. Digestive and liver diseases statistics in several referral centers in Tehran, 2000-2004. Govaresh 2006; 11(1): 33-8.
[5]
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 2006; 160(1): 1-40.
[http://dx.doi.org/10.1016/j.cbi.2005.12.009] [PMID: 16430879]
[6]
Gomes EC, Silva AN, Oliveira MR. Oxidants, antioxidants, and the beneficial roles of exercise-induced production of reactive species. Oxid Med Cell Longev 2012; 2012: 1-12.
[http://dx.doi.org/10.1155/2012/756132] [PMID: 22701757]
[7]
Zarei S, Hosseiniara SM. Selenium as a mineral with anti-cancer properties. Novel Clin Med 2022; 1(1): 4-25.
[http://dx.doi.org/10.22034/ncm.2022.140283]
[8]
Hasani D, Bahrami M, Ghasemifard L. Food pyramid according to persian medicine’s point of view and its comparison with modern medicine. Novel Clin Med 2022; 1(3): 163-5.
[http://dx.doi.org/10.22034/ncm.2022.327031.1008]
[9]
Higuera-Ciapara I, Félix-Valenzuela L, Goycoolea FM. Astaxanthin: A review of its chemistry and applications. Crit Rev Food Sci Nutr 2006; 46(2): 185-96.
[http://dx.doi.org/10.1080/10408690590957188] [PMID: 16431409]
[10]
Fassett RG, Coombes JS. Astaxanthin: A potential therapeutic agent in cardiovascular disease. Mar Drugs 2011; 9(3): 447-65.
[http://dx.doi.org/10.3390/md9030447] [PMID: 21556169]
[11]
Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nat Rev Cancer 2003; 3(5): 330-8.
[http://dx.doi.org/10.1038/nrc1074] [PMID: 12724731]
[12]
Letchford K, Burt H. A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: Micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 2007; 65(3): 259-69.
[http://dx.doi.org/10.1016/j.ejpb.2006.11.009] [PMID: 17196803]
[13]
Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 2012; 64: 24-36.
[http://dx.doi.org/10.1016/j.addr.2012.09.006] [PMID: 12204596]
[14]
Cho K, Wang X, Nie S, Chen ZG, Shin DM. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 2008; 14(5): 1310-6.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1441] [PMID: 18316549]
[15]
Gholami H, Divsalar A, Abbasalipourkabir R, Ziamajidi N, Saeidifar M. The simultaneous carrier ability of natural antioxidant of astaxanthin and chemotherapeutic drug of 5-fluorouracil by whey protein of β lactoglobulin: Spectroscopic and molecular docking study. J Biomol Struct Dyn 2021; 39(3): 1004-16.
[http://dx.doi.org/10.1080/07391102.2020.1733091] [PMID: 32081089]
[16]
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72(1-2): 248-54.
[http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]
[17]
Hadwan MH, Abed HN. Data supporting the spectrophotometric method for the estimation of catalase activity. Data Brief 2016; 6: 194-9.
[http://dx.doi.org/10.1016/j.dib.2015.12.012] [PMID: 26862558]
[18]
Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70(1): 158-69.
[PMID: 6066618]
[19]
Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974; 47(3): 469-74.
[http://dx.doi.org/10.1111/j.1432-1033.1974.tb03714.x] [PMID: 4215654]
[20]
Liu X, Song M, Gao Z, et al. Stereoisomers of astaxanthin inhibit human colon cancer cell growth by inducing G2/M cell cycle arrest and apoptosis. J Agric Food Chem 2016; 64(41): 7750-9.
[http://dx.doi.org/10.1021/acs.jafc.6b03636] [PMID: 27726394]
[21]
Hormozi M, Ghoreishi S, Baharvand P. Astaxanthin induces apoptosis and increases activity of antioxidant enzymes in LS-180 cells. Artif Cells Nanomed Biotechnol 2019; 47(1): 891-5.
[http://dx.doi.org/10.1080/21691401.2019.1580286] [PMID: 30873887]
[22]
Tang G, Yang J, Minemoto Y, Lin A. Blocking caspase-3-mediated proteolysis of IKKbeta suppresses TNF-α induced apoptosis. Mol Cell 2001; 8(5): 1005-16.
[http://dx.doi.org/10.1016/S1097-2765(01)00380-X] [PMID: 11741536]
[23]
Tanaka T, Makita H, Ohnishi M, Mori H, Satoh K, Hara A. Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls, astaxanthin and canthaxanthin. Cancer Res 1995; 55(18): 4059-64.
[PMID: 7664280]
[24]
Muto Y, Fujii J, Shidoji Y, Moriwaki H, Kawaguchi T, Noda T. Growth retardation in human cervical dysplasia-derived cell lines by beta-carotene through down-regulation of epidermal growth factor receptor. Am J Clin Nutr 1995; 62(6) (Suppl.): S1535-40.
[http://dx.doi.org/10.1093/ajcn/62.6.1535S] [PMID: 7495256]
[25]
Teng Z, Xu R, Wang Q. Beta-lactoglobulin-based encapsulating systems as emerging bioavailability enhancers for nutraceuticals: A review. RSC Advances 2015; 5(44): 35138-54.
[http://dx.doi.org/10.1039/C5RA01814E]
[26]
Ekpe L, Inaku K, Ekpe V. Antioxidant effects of astaxanthin in various diseases— A review. J Mol Pathophysiol 2018; 7(1): 1-6.
[http://dx.doi.org/10.5455/jmp.20180627120817]
[27]
Zhang L, Wang H. Multiple mechanisms of anti-cancer effects exerted by astaxanthin. Mar Drugs 2015; 13(7): 4310-30.
[http://dx.doi.org/10.3390/md13074310] [PMID: 26184238]
[28]
Genç Y, Bardakci H, Yücel Ç,. Oxidative stress and marine carotenoids: Application by using nanoformulations. Mar Drugs 2020; 18(8): 423.
[http://dx.doi.org/10.3390/md18080423] [PMID: 32823595]
[29]
Wu D, Xu H, Chen J, Zhang L. Effects of astaxanthin supplementation on oxidative stress. Int J Vitam Nutr Res 2020; 90(1-2): 179-94.
[http://dx.doi.org/10.1024/0300-9831/a000497] [PMID: 30982442]
[30]
Ogasawara M, Matsunaga T, Suzuki H. Differential effects of antioxidants on the in vitro invasion, growth and lung metastasis of murine colon cancer cells. Biol Pharm Bull 2007; 30(1): 200-4.
[http://dx.doi.org/10.1248/bpb.30.200] [PMID: 17202688]

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