Volume 36, Issue 3 (9-2025)                   Studies in Medical Sciences 2025, 36(3): 186-194 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Torabi P, Rostami Motamed H, Ebadi M. Investigation of the Effects of 5-Fluorouracil and Green Synthesized Silver Chloride Nanoparticles on Embryonic Kidney Cells (HEK293). Studies in Medical Sciences 2025; 36 (3) :186-194
URL: http://umj.umsu.ac.ir/article-1-6443-en.html
Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran , aic.intl.conferences@gmail.com
Abstract:   (57 Views)
 Abstract
Background & Aim:
Despite its anticancer efficacy, 5-Fluorouracil exhibits toxicity toward normal cells. Similarly, silver chloride nanoparticles (AgCl NPs), although known for their anticancer potential, raise safety concerns. Due to limited data on the combined effects of these two agents on normal renal cells, this study aimed to evaluate the individual and combined cytotoxic effects of 5-Fluorouracil and AgCl NPs on HEK293 cells.
Materials & Methods:
HEK293 cells were treated with various concentrations of 5-Fluorouracil, AgCl NPs, and their combination. Cell viability was assessed using the MTT assay, and IC₅₀ values were calculated. Statistical analysis was performed using one-way ANOVA and Tukey’s post hoc test.
Results:
All treatments reduced cell viability in a dose-dependent manner. IC₅₀ values were calculated as 125 µg/ml for AgCl NPs, 174 µg/ml for 5FU, and 181 µg/ml for the combination. The combined treatment exhibited a higher IC₅₀ than either single agent, suggesting potential protective interactions.
Conclusion:
Co-treatment with 5-Fluorouracil and AgCl NPs may reduce cytotoxicity to normal cells while maintaining therapeutic efficacy. These findings highlight the need for further in vivo studies and mechanistic investigations to optimize safe and effective nanoformulation-based therapies.
 
Full-Text [PDF 916 kb]   (27 Downloads)    
Type of Study: Research | Subject: فیزیولوژی

References
1. Ghafouri-Fard S, Abak A, Tondro Anamag F, Shoorei H, Fattahi F, Javadinia SA, et al. 5-Fluorouracil: A Narrative Review on the Role of Regulatory Mechanisms in Driving Resistance to This Chemotherapeutic Agent. Front Oncol. 2021;11:658636. doi: 10.3389/fonc.2021.658636 [DOI:10.3389/fonc.2021.658636] [PMID] []
2. Moutabian H MM, Ghahramani-Asl R, Yadollahi M, Gharepapagh E, Ataei G, et al. A systematic review of the therapeutic effects of resveratrol in combination with 5-fluorouracil during colorectal cancer treatment: with a special focus on the oxidant, apoptotic, and anti-inflammatory activities. Cancer Cell Int. 2022;22(1):142. doi: 10.1186/s12935-022-02561-7 [DOI:10.1186/s12935-022-02561-7] [PMID] []
3. Vidyasagar, Patel RR, Singh SK, Singh M. Green synthesis of silver nanoparticles: methods, biological applications, delivery and toxicity. Mater Adv. 2023;4(8):1831-49. doi: 10.1039/D2MA01105K [DOI:10.1039/D2MA01105K]
4. Durán N, Nakazato G, Seabra AB. Antimicrobial activity of biogenic silver nanoparticles, and silver chloride nanoparticles: an overview and comments. Appl Microbiol Biotechnol. 2016;100(15):6555-70. doi: 10.1007/s00253-016-7657-7 [DOI:10.1007/s00253-016-7657-7] [PMID]
5. Ahmad A, Haneef M, Ahmad N, Kamal A, Jaswani S, Khan F. Biological synthesis of silver nanoparticles and their medical applications. World Academy of Sciences Journal. 2024;20;6(3):22. doi: 10.3892/wasj.2024.237 [DOI:10.3892/wasj.2024.237]
6. Stepanenko AA, Dmitrenko VV. HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution. Gene. 2015;569(2):182-90. doi: 10.1016/j.gene.2015.05.065 [DOI:10.1016/j.gene.2015.05.065] [PMID] []
7. Tan E, Chin CSH, Lim ZFS, Ng SK. HEK293 Cell Line as a Platform to Produce Recombinant Proteins and Viral Vectors. Front Bioeng Biotechnol. 2021;9:796991. doi: 10.3389/fbioe.2021.796991 [DOI:10.3389/fbioe.2021.796991] [PMID] []
8. Arabnezhad S, Mani H, Gordi P, Ahmadi R. The Cytotoxic Effects of 5FU on Hek293 and HeLa Cells in vitro. International Journal of BioLife Sciences (IJBLS). 2022;1(3):128-33. [GOOGLE SCHOLAR]
9. Bigdeli R, Shahnazari M, Panahnejad E, Cohan RA, Dashbolaghi A, Asgary V. Cytotoxic and apoptotic properties of silver chloride nanoparticles synthesized using Escherichia coli cell-free supernatant on human breast cancer MCF 7 cell line. Artif Cells Nanomed Biotechnol. 2019;47(1):1603-9. doi: 10.1080/21691401.2019.1604533 [DOI:10.1080/21691401.2019.1604533] [PMID]
10. Salman G, Pehlivanoglu S, Aydin Acar C, Yesilot S. Anticancer Effects of Vitis vinifera L. Mediated Biosynthesized Silver Nanoparticles and Cotreatment with 5 Fluorouracil on HT-29 Cell Line. Biol Trace Elem Res. 2022;200(7):3159-70. doi: 10.1007/s12011-021-02923-8 [DOI:10.1007/s12011-021-02923-8] [PMID]
11. Muhamad M ARN, Wan Omar WA, Nik Mohamed Kamal NN. . Cytotoxicity and Genotoxicity of Biogenic Silver Nanoparticles in A549 and BEAS‐2B Cell Lines. . Bioinorg Chem Appl. 2022;2022(1):8546079. doi: 10.1155/2022/8546079 [DOI:10.1155/2022/8546079] [PMID] []
12. Danışman-Kalındemirtaş F, Kariper İA, Üstündağ H, Özsoy C, Erdem-Kuruca S. Antiproliferative effects of 5FU-AgNPs on different breast cancer cells. Journal of Taibah University for Science. 2024;18(1):2354573. doi: 10.1080/16583655.2024.2354573 [DOI:10.1080/16583655.2024.2354573]
13. Pereira M, Vale N. Repurposing Alone and in Combination of the Antiviral Saquinavir with 5-Fluorouracil in Prostate and Lung Cancer Cells. Int J Mol Sci. 2022;23(20):12240. doi: 10.3390/ijms232012240 [DOI:10.3390/ijms232012240] [PMID] []
14. Yusefi M SK, Jahangirian H, Teow SY, Umakoshi H, Saleh B, Rafiee-Moghaddam R, Webster TJ. The potential anticancer activity of 5-fluorouracil loaded in cellulose fibers isolated from rice straw. Int J Nanomedicine. 2020;29:5417-32. doi: 10.2147/IJN.S250047 [DOI:10.2147/IJN.S250047] [PMID] []
15. ABD ELATY FT, El-Amir YO, ABDEL RAHMAN MK, Hassan AS. Histopathological and biochemical evaluation of hepatotoxicity and nephrotoxicity induced by 5-fluorouracil in rats. Assiut Veterinary Medical Journal. 2023;69(178):145-54. doi: 10.21608/avmj.2023.213997.1148 [DOI:10.21608/avmj.2023.213997.1148]
16. Lamberti M, Porto S, Zappavigna S, Stiuso P, Tirino V, Desiderio V, et al. Levofolene modulates apoptosis induced by 5-fluorouracil through autophagy inhibition: Clinical and occupational implications. Int J Oncol. 2015;46(5):1893-900. doi: 10.3892/ijo.2015.2904 [DOI:10.3892/ijo.2015.2904] [PMID] []
17. Francipane MG, Bulanin D, Lagasse E. Establishment and Characterization of 5-Fluorouracil-Resistant Human Colorectal Cancer Stem-Like Cells: Tumor Dynamics under Selection Pressure. Int J Mol Sci. 2019;20(8):1817. doi: 10.3390/ijms20081817 [DOI:10.3390/ijms20081817] [PMID] []
18. Focaccetti C, Bruno A, Magnani E, Bartolini D, Principi E, Dallaglio K, et al. Effects of 5-Fluorouracil on Morphology, Cell Cycle, Proliferation, Apoptosis, Autophagy and ROS Production in Endothelial Cells and Cardiomyocytes. PLoS One. 2015;10(2):e0115686. doi: 10.1371/journal.pone.0115686 [DOI:10.1371/journal.pone.0115686] [PMID] []
19. Midena E, Lazzarini D, Catania AG, Moretto E, Fregona I, Parrozzani R. Cytostatic and Cytotoxic Effects of 5-Fluorouracil on Human Corneal Epithelial Cells and Keratocytes. Cornea. 2013;32(3):338-44. doi: 10.1097/ICO.0b013e31825d56c1 [DOI:10.1097/ICO.0b013e31825d56c1] [PMID]
20. Jiang X, Lu C, Tang M, Yang Z, Jia W, Ma Y, et al. Nanotoxicity of Silver Nanoparticles on HEK293T Cells: A Combined Study Using Biomechanical and Biological Techniques. ACS Omega. 2018;3(6):6770-8. doi: 10.1021/acsomega.8b00608 [DOI:10.1021/acsomega.8b00608] [PMID] []
21. Ardalani S, Ahmadi R, Torabi P. The cytotoxic effects of green synthesized AgCl2 nanoparticles on gastric cancer (AGS) cells. Journal of Biological Studies. 2022;5(3):673-6. doi: 10.62400/jbs.v5i3.7089 [DOI:10.62400/jbs.v5i3.7089]
22. Jafari M. The Effects of Green Synthesized Silver Nano-Particles on Mesenchymal Stem Cells Apoptosis. International Journal of BioLife Sciences. 2023;2(1):90. [GOOGLE SCHOLAR]
23. Shali R, Neamati A, Ardalan P. Investigating the Cytotoxic Effect and Antioxidant Properties of Green Synthesized Silver Nanoparticles from the Root of Persicaria Bistorta on Human Liver Cancer Cell Line (Hep G2). Journal of Ilam University of Medical Sciences. 2018;26(6):133-42. doi: 10.29252/sjimu.26.6.133 [DOI:10.29252/sjimu.26.6.133]
24. Onodera A, Nishiumi F, Kakiguchi K, Tanaka A, Tanabe N, Honma A, et al. Short-term changes in intracellular ROS localisation after the silver nanoparticles exposure depending on particle size. Toxicol Rep. 2015;2:574-9. doi: 10.1016/j.toxrep.2015.03.004 [DOI:10.1016/j.toxrep.2015.03.004] [PMID] []
25. Zhang J, Wang F, Yalamarty SSK, Filipczak N, Jin Y, Li X. Nano Silver-Induced Toxicity and Associated Mechanisms. Int J Nanomedicine. 2022;17:1851-64. doi: 10.2147/IJN.S355131 [DOI:10.2147/IJN.S355131] [PMID] []
26. Güzel D, Güneş M, Yalçın B, Akarsu E, Rencüzoğulları E, Kaya B. Genotoxic potential of different nano-silver halides in cultured human lymphocyte cells. Drug Chem Toxicol. 2023;46(4):768-80. doi: 10.1080/01480545.2022.2096056 [DOI:10.1080/01480545.2022.2096056] [PMID]
27. Gavamukulya Y, Maina EN, El-Shemy HA, Meroka AM, Kangogo GK, Magoma G, et al. Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through the regulation of CASP9 and the CXCL1/CXCR2 genes axis. Tumour Biol. 2021;43(1):37-55. doi: 10.3233/TUB-200058 [DOI:10.3233/TUB-200058] [PMID]
28. Tawfeeq AT, Jodou AS, Hamad BS. Comparative Assessment of Silver Nanoparticles Impact on Normal and Cancer Cells in Vitro. 2024. doi: 10.2139/ssrn.4874449 [DOI:10.2139/ssrn.4874449]
29. Yuan J, Khan SU, Luo J, Jiang Y, Yang Y, Yan J, et al. Biosynthetic Silver Nanoparticles Inhibit the Malignant Behavior of Gastric Cancer Cells and Enhance the Therapeutic Effect of 5-Fluorouracil by Promoting Intracellular ROS Generation and Apoptosis. Pharmaceutics. 2022;14(10):2109. doi: 10.3390/pharmaceutics14102109 [DOI:10.3390/pharmaceutics14102109] [PMID] []
30. Kaya MM. Silver nanoparticles stimulate 5‐Fluorouracil‐induced colorectal cancer cells to kill through the upregulation TRPV1‐mediated calcium signaling pathways. Cell Biol Int. 2024;48(5):712-25. doi: 10.1002/cbin.12141 [DOI:10.1002/cbin.12141] [PMID]
31. Matai I, Sachdev A, Gopinath P. Multicomponent 5-fluorouracil loaded PAMAM stabilized-silver nanocomposites synergistically induce apoptosis in human cancer cells. Biomater Sci. 2015;3(3):457-68. doi: 10.1039/C4BM00360H [DOI:10.1039/C4BM00360H] [PMID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.