Evaluation of antitumor efficacy of Cerium oxide nanoparticle on Ehrlich tumour cells in mice
Main Article Content
Keywords
CeNPs-cisplatin. Ehrlich tumour. P-53- K-Ras- antioxidant enzymes
Abstract
The goal of the current study was to assess the anticancer effects of cisplatin and cerium oxide nanoparticles on tumours caused by Ehrlich tumour cells in the skeletal muscles of female mice. The Ehrlich solid carcinoma bearing female mice were divided into 5 groups, control group Ehrlich solid carcinoma bearing mice were administered deionized dist. water for two weeks, Group 2 orally administered with ( 5%CeNPs) Group 3: orally administered with ( 10%CeNPs) Group 4: orally administered with ( 20%CeNPs) Group 5: Ehrlich solid carcinoma bearing mice were injected intra-peritoneal with Cisplatin (1 mg/kg) daily for two weeks. Antioxidant parameters, comet assay, histopathology, and mRNA expression of (P53 and K-ras ) genes were evaluated. The tumour mass was consisted of sheets and clusters of neoplastic cells with small areas of necrosis. The addition of cerium oxide nanoparticles lead to diminished the tumour masses and appearance of apoptotic holes. In the first group, the present study found higher levels of malondialdehyde (MDA) and decreased activity of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). The addition of 20% CeNPs resulted in a drop in MDA and an increase in SOD, while the activity of the GPx enzymes increased. The K-Ras gene was up-regulated by the CeNPs, but the P53 gene was down-regulated. Cisplatin also showed similar results to cerium oxide nanoparticles but less prominent. The cerium oxide nanoparticle had antitumor efficacy as that of the cisplatin with low side effects on the tissues.
References
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7. Park E.J., J. Choi, Y.K. Park, K. Park,Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells, Toxicology 245 (2008) 90–100. DOI: 10.1016/j.tox.2007.12.022
8. Hamrahi-Michak M, S.A. Sadeghi, H. Haghighi, Y. Ghanbari-Kakavandi, S.A. Razavi-sheshdeh, M. Torkamani Noughabi, M. Negahdary, The toxicity effect of cerium oxide nanoparticles on blood cells of male rat, Ann. Biol. Res. 3 (2012) 2859–2866. DOI: 10.1016/j.cbi.2015.03.013
9. Asati A, S. Santra, C. Kaittanis, J.M. Perez, Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles, ACS Nano 4 (2010) 5321–5331. DOI: 10.1021/nn100816s
10. Ying Gao, Kan Chen, Jin-lu Ma, and Fei Gao, Cerium oxide nanoparticles in cancer. Onco Targets Ther. 2014; 7: 835–840. doi: 10.2147/OTT.S62057
11. Rosenberg, B, In Nucleic Acid-Metal Ion Interactions; Spiro, T.G., Ed.; John Wiley & Sons, Inc.: New York, NY, USA, 1980; Volume1, pp. 1–29.
12. Desoize, B.; Madoulet, C, Particular aspects of platinum compounds used at present in cancer treatment. Crit. Rev. Oncol. Hematol. 2002, 42, 317–325. DOI: 10.1016/s1040-8428(01)00219-0
13. Shaloam Dasari 1, Paul Bernard Tchounwou, Cisplatin in cancer therapy: molecular mechanisms of action j.ejphar.2014.07.025. Epub 2014 Jul 21.DOI: 10.1016/j.ejphar.2014.07.025
14. Sumit Ghosh, Cisplatin: The first metal based anticancer drug. j.bioorg.2019.102925. Epub 2019 Apr 11. DOI: 10.1016/j.bioorg.2019.102925
15. Ana-Maria Florea and Dietrich Büsselberg, Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects. Cancers 2011, 3, 1351-1371; doi:10.3390/cancers3011351
16. Chen, Y., Han, F., Cao, L. H., Li, C., Wang, J. W., Li, Q.& Zhou, J. H, Dose-response relationship in cisplatin-treated breast cancer xenografts monitored with dynamic contrast-enhanced ultrasound. BMC cancer, 2015.15(1), 1-9. doi: 10.1186/s12885-015-1170-8
17. Tice, R. R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., & Sasaki, Y. F, Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environmental and molecular mutagenesis, 2000.35(3), 206-221. doi: 10.1002/(sici)1098-2280(2000)35:3<206::aid-em8>3.0.co;2-j.
18. Bancroft, J. D., and Layton, C, The hematoxylin and eosin, connective and mesenchymal tissues with their stains,” in Bancroft s Theory and Practice of Histological Techniques, eds K. S. Suvarna, C. Layton, and J. D. Bancroft (Philadelphia, PA: Churchill Livingstone),2013. 173–186.
19. Ohkawa, H., Ohishi, N., & Yagi, K,Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry,1979. 95(2), 351-358.
20. Abdel-Mawla, M. Y., Nofal, E., Khalifa, N., Abdel-Shakoor, R., & Nasr, Role of oxidative stress in psoriasis: An evaluation study. J Am Sci, 2013. 9, 151-5. http://www.jofamericanscience.org.
21. Paglia, D. E., & Valentine, W. N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. The Journal of laboratory and clinical medicine, 70(1), 158-169. PMID: 6066618
22. Farahmandjou, M., Zarinkamar, M. , Firoozabadi, T. P, Synthesis of Cerium Oxide (CeO2) nanoparticles using simple CO-precipitation method. Rev. Mex. Fis.2016. 62, 496–499
23. Paolino D, Fresta M, Sinha P, Ferrari M,Drug delivery systems. In: Webester JG, editor. Encyclopedia of medical devices and
instrumentation. 2nd ed. John Wiley and Sons; 2006. p. 437–95.
24. Gutteridge, J. M., and Halliwell, B, Free radicals and antioxidants in the year 2000: a historical look to the future. Ann. N. Y. Acad. Sci. 899, 136–147. doi: 10.1111/j.1749-6632.2000.tb06182.x
25. Ighodaro, O., and Akinloye, O, First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria J. Med. 54, 2018.287–293. doi: 10.1016/j.ajme.2017.09.001
26. Chen, Q., Niu, Y., Zhang, R., Guo, H., Gao, Y., Li, Y., et al, The toxic influence of paraquat on hippocampus of mice: involvement of oxidative stress. Neurotoxicology 31, 310–316. doi: 10.1016/j.neuro.2010.02.006
27. Elshony Norhan , Atef M. K. Nassar, Yasser S. El-Sayed, Dalia Samak,
28. Ahmed Noreldin, Lamiaa Wasef, Hamida Saleh, Yaser H. A. Elewa,Shereen E. Tawfeek, Abdullah A. Saati, Gaber, Ameliorative Role of Cerium Oxide Nanoparticles Against Fipronil Impact on Brain Function, Oxidative Stress, and Apoptotic Cascades in Albino Rats. Frontiers in Neuroscience | www.frontiersin.org 2 May 2021 | Volume 15 . DOI: 10.3389/fnins.2021.651471
29. Dasari, S., and Tchounwou, P. B, Cisplatin in cancer therapy: molecular mechanisms of action. Eur. J. Pharmacol. 740, 364–378. doi:10.1016/j.ejphar. 2014.07.025
30. Prasad R and SB Prasad,Histoprotective effect of rutin against cisplatin-induced toxicities in tumor-bearing mice: Rutin lessens cisplatin-induced toxicities. Human and Experimental Toxicology 2021, Vol. 40(2) 245–258. DOI: 10.1177/0960327120947793
31. Barabas, K., Milner, R., Lurie, D., and Adin, C, Cisplatin: a review of toxicities and therapeutic applications. Vet. Comp. Oncol.,2008. 6 (1), 1. doi:10.1111/ j.1476-5829.2007.00142.x
32. Omar, H. A.,Mohamed,W. R., Arab, H. H., and Arafa, E.-S. A,Tangeretin alleviates cisplatin-induced acute hepatic injury in rats: targeting MAPKs and apoptosis. PLoS One 2016. 11 (3), doi:10.1371/journal.pone.0151649
33. Qi, L., Luo, Q., Zhang, Y., Jia, F., Zhao, Y., and Wang, F, Advances in toxicological research of the anticancer drug cisplatin. Chem. Res. Toxicol. 2019.32 (8), 1469–1486. DOI: 10.1021/acs.chemrestox.9b00204
34. Abouzeinab, N. S, Antioxidant effect of silymarin on cisplatin-induced renal oxidative stress in rats. J Pharmacol Toxicol, 2015. 10(1), 1-19. DOI: 10.3923/jpt.2015.1.19
35. Karakoc, H. T., Altintas, R., Parlakpinar, H., Polat, A., Samdanci, E., Sagir, M., & Duran, Z. R, Protective Effects of Molsidomine Against Cisplatin-Induced Nephrotoxicity. Advances inclinical and experimental medicine: official organ Wroclaw Medical University, 2015.24(4), 585-593. doi: 10.17219/acem/47742
36. Colon J, N. Hsieh, A. Ferguson, P. Kupelian, S. Seal, D.W. Jenkins, C.H. Baker , Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2, Nanomedicine 6 (2010) 698–705. DOI: 10.1016/j.nano.2010.01.010
37. Kong L, Cai X, Zhou X, Wong LL, Karakoti AS, Seal S, et al, Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis/survival signaling pathways. Neurobiol Dis 2011; 42(3): 514-23. DOI: 10.1016/j.nbd.2011.03.004
38. Giri S, Karakoti A, Graham RP, Maguire JL, Reilly CM, Seal S, et al, Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer. PloS One 2013; 8(1). https://doi.org/10.1371/journal.pone.0054578
39. Waris G, H. Ahsan, Reactive oxygen species: role in the development of cancer and various chronic conditions, J. Carcinog. 5 (2006) 14. doi: 10.1186/1477-3163-5-14
40. Elswaifi S.F., J.R. Palmieri, K.S. Hockey, B.A. Rzigalinski, Antioxidant nanoparticles for control of infectious disease, Infect. Disord. Drug Targets 9 (2009) 445–452. DOI: 10.2174/187152609788922528
41. Alili L, M. Sack, A.S. Karakoti, S. Teuber, K. Puschmann, S.M. Hirst, C.M. Reilly, K. Zanger, W. Stahl, S. Das, S. Seal, P. Brenneisen, Combined cytotoxic and anti-invasive properties of redox active nanoparticles in tumor–stroma interactions, Biomaterials 32 (2011) 2918–2929. DOI: 10.1016/j.biomaterials.2010.12.056
42. Wason M.S, J. Colon, S. Das, S. Seal, J. Turkson, J. Zhao, C.H. Baker, Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production, Nanomedicine 9 (2013) 558–569. DOI: 10.1016/j.nano.2012.10.010
43. Madero-Visbal R.A, B.E. Alvarado, J.F. Colon, C.H. Baker, M.S. Wason, B. Isley, S.Seal, C.M. Lee, S. Das, R. Manon, Harnessing nanoparticles to improve toxicity after head and neck radiation, Nanomedicine 8 (2012) 1223–1231. DOI: 10.1016/j.nano.2011.12.011
44. Milica Pešic´ , Ana Podolski-Renic´ , Sonja Stojkovic´ , Branko Matovic´ , Danica Zmejkoski , Vesna Kojic´ , Gordana Bogdanovic´ , Aleksandra Pavic´evic´ , Miloš Mojovic´ , Aleksandar Savic´ , Ivana Milenkovic´ , Aleksandar Kalauzi , Ksenija Radotic , Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. Chemico-Biological Interactions 232 (2015) 85–93. https://www.researchgate.net/deref/http%3A%2F%2Fdx.doi.org%2F10.1016%2Fj.cbi.2015.03.013
45. Wang, J., Yang, W., He, X., Zhang, Z., & Zheng, X, Assembling p53 activating peptide with CeO2 nanoparticle to construct a metallo-organic supermolecule toward the synergistic ferroptosis of tumor. Frontiers in Bioengineering and Biotechnology, 2022.10. https://doi.org/10.3389/fbioe.2022.929536
46. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B 1997. A model for p53-induced apoptosis. Nature (Lond.) 1997;389:300 –5. DOI: 10.1038/38525
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Mar 29, 2023
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S.M. AbdEl-Aziz, A.A. Baiomy, A. B. Mansour, R. H. Hanan, S. A. Ali, H. F. Attia, & Gehan B. A. Youssef. (2023). Evaluation of antitumor efficacy of Cerium oxide nanoparticle on Ehrlich tumour cells in mice. Journal of Population Therapeutics and Clinical Pharmacology, 30(5), 378–390. https://doi.org/10.47750/jptcp.2023.30.05.039
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