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Assessment of mechanism involved in the apoptotic and anti-cancer activity of Quercetin and Quercetin-loaded chitosan nanoparticles

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Abstract

In prior studies, Quercetin was revealed to exhibit anti-cancer features in a variety of cancer cell lines. However, the impact of Quercetin on neuroblastoma is unknown. This study looked into the potential cytotoxic effects of Quercetin and Quercetin-loaded chitosan nanoparticles (NPs) on the SH-SY5Y cell line. In this study, NPs containing Quercetin was prepared and characterization studies were performed. The vitality of the cells was measured using the XTT test after 24 h of treatment with various concentrations of Quercetin (0.5, 1, 2, 4, and 8 µg/mL). ELISA kits were used to detect the amounts of cleaved PARP, BCL-2, 8-Hydroxy-deoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant status, and total antioxidant status in the cells. The results of the chitosan NPs characterization investigation revealed that the particle size, encapsulation effectiveness, and drug release profile of NPs were all appropriate for cell culture studies. Quercetin and Quercetin-loaded chitosan NPs significantly reduced cell viability in SH-SY5Y cells at different concentrations (**p < 0.05). 2 µg/mL Quercetin and Quercetin-loaded chitosan NPs significantly enhanced the levels of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP, and total oxidant in ELISA testing. However, treatment with 2 µg/mL of Quercetin and Quercetin-loaded chitosan NPs did not affect the amount of BCL-2 protein. Overall, Quercetin and Quercetin-loaded chitosan NPs caused significant cytotoxicity in SH-SY5Y cells via producing oxidative stress, DNA damage, and eventually apoptosis.

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References

  1. Docea AO, Mitrut P, Grigore D, Pirici D, Calina DC, Gofita E. Immunohistochemical expression of TGF beta (TGF-beta), TGF beta receptor 1 (TGFBR1), and Ki67 in intestinal variant of gastric adenocarcinomas. Rom J Morphol Embryol. 2012;53(3):683–92.

    PubMed  Google Scholar 

  2. Salehi B, Jornet PL, Lopez EPF, Calina D, Sharifi-Rad M, Ramirez-Alarcon K, Forman K, Fernandez M, Martorell M, Setzer WN, et al. Plant-derived bioactives in oral mucosal lesions: a key emphasis to curcumin, lycopene, chamomile, aloe vera green tea and coffee properties. Biomolecules. 2019;9(3):1–23.

    Article  Google Scholar 

  3. Sharifi-Rad M, Kumar NVA, Zucca P, Varoni EM, Dini L, Panzarini E, Rajkovic J, Fokou PVT, Azzini E, Peluso I, et al. Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Front Physiol. 2020;11:1–21.

    Article  Google Scholar 

  4. Ghad A, Mahjoub S, Tabandeh F, Talebnia F. Synthesis and optimization of chitosan nanoparticles: potential applications in nanomedicine and biomedical engineering. Caspian J Intern Med. 2014;5:156–61.

    Google Scholar 

  5. Park W, Heo YJ, Han DK. New opportunities for nanoparticles in cancer immunotherapy. Biomater Res. 2018;22:24–33. https://doi.org/10.1186/s40824-018-0133-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jovčevska I, Muyldermans S. The therapeutic potential of nanobodies. BioDrugs Clin Immunotherap Biopharm Gene Therapy. 2020;34(1):11–26. https://doi.org/10.1007/s40259-019-00392-z.

    Article  CAS  Google Scholar 

  7. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8(1):59–73. https://doi.org/10.1038/nri2216.

    Article  CAS  PubMed  Google Scholar 

  8. Wang R, Billone PS, Mullett WM. Nanomedicine in action: an overview of cancer nanomedicine on the market and in clinical trials. J Nanomater. 2013;2013:1–12.

    Google Scholar 

  9. Adair JH, Parette MP, Altinoglu EI, Kester M. Nanoparticulate alternatives for drug delivery. ACS Nano. 2010;4(9):4967–70.

    Article  CAS  Google Scholar 

  10. Altinoglu EI, Adair JH. Near infrared imaging with nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010;2(5):461–77.

    Article  CAS  Google Scholar 

  11. Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Drug Resist. 2019;2:141–60.

    Google Scholar 

  12. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: a brief review. Tabriz Univ Med Sci. 2017;7:339–48.

    CAS  Google Scholar 

  13. Longacre M, Snyder N, Sarkar S. Drug resistance in cancer: an overview. Cancers (Basel). 2014;6:1769–92.

    Article  Google Scholar 

  14. Xue X, Liang XJ. Overcoming drug efflux-based multidrug resistance in cancer with nanotechnology. Chin J Cancer. 2012;31:100–9.

    Article  CAS  Google Scholar 

  15. Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of efflux pumps in multidrug-resistant cancer. Nat Rev Cancer. 2018;18:452–64.

    Article  CAS  Google Scholar 

  16. Singh A, Benjakul S, Prodpran T. Ultrasound assisted extraction of chitosan from squid pen: molecular characterization and fat binding capacity. J Food Sci. 2019;84:224–34.

    Article  CAS  Google Scholar 

  17. Mittal A, Singh A, Benjakul S, Prodpran T, Nilsuwan K, Huda N, Caba KDL. Composite films based on chitosan and epigallocatechin gallate grafted chitosan: characterization, antioxidant and antimicrobial activities. Food Hydrocol. 2020;111:1–10.

    Google Scholar 

  18. Singh A, Benjakul S, Prodpran T. Chitooligosaccharides from squid pen prepared using different enzymes: characteristics and the effect on quality of surimi gel during refrigerated storage. Food Prod Process Nutri. 2019;1:1–10.

    Article  Google Scholar 

  19. Li J, Cai C, Ja L. Chitosan-based nanomaterials for drug delivery. Molecules. 2018;23:2661. https://doi.org/10.3390/molecules23102661.

    Article  CAS  PubMed Central  Google Scholar 

  20. Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev. 2010;62(1):83–99. https://doi.org/10.1016/j.addr.2009.07.019.

    Article  CAS  PubMed  Google Scholar 

  21. Torabi N, Dobakhti F, Faghihzadeh S, Haniloo A. In vitro and in vivo effects of chitosan-praziquantel and chitosan-albendazole nanoparticles on Echinococcus granulosus Metacestodes. Parasitol Res. 2018;117:2015–23. https://doi.org/10.1007/s00436.

    Article  PubMed  Google Scholar 

  22. Jhaveri J, Raichura Z, Khan T, Momin M, Omri A. Chitosan nanoparticles-insight into properties, functionalization and applications in drug delivery and theranostics. Molecules. 2021;26:272. https://doi.org/10.3390/molecules26020272.

    Article  CAS  PubMed Central  Google Scholar 

  23. Cheimonidi C, Samara P, Polychronopoulos P, et al. Selective cytotoxicity of the herbal substance acteoside against tumor cells and its mechanistic insights. Redox Biol. 2018;16:169–78.

    Article  CAS  Google Scholar 

  24. Tavana E, Mollazadeh H, Mohtashami E, et al. Quercetin: A promising phytochemical for the treatment of glioblastoma multiforme. BioFactors. 2020;46:356–66.

    Article  CAS  Google Scholar 

  25. Taskin T, Dogan M, Yilmaz BN, Senkardes I. Phytochemical screening and evaluation of antioxidant, enzyme inhibition, anti-proliferative and calcium oxalate anti-crystallization activities of Micromeria fruticosa spp. brachycalyx and Rhus coriaria. Biocatal Agric Biotechnol. 2020;27:1–7.

    Article  Google Scholar 

  26. Calvo P, Remunan-Lopez C, Vila-Jato JL, Alonso MJ. Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J Appl Polym Sci. 1997;63(1):125–32.

    Article  CAS  Google Scholar 

  27. Wikanta T, Erizal T, Tjahyono T, Sugiyono T. Synthesis of polyvinyl alcohol-chitosan hydrogel and study of its swelling and antibacterial properties. Squalen Bull Mar Fish Postharvest Biotechnol. 2012;7(1):1–10.

    Google Scholar 

  28. Purbowatiningrum N, Ismiyarto EF. Cinnamomum casia extract encapsulated nanochitosan as antihypercholesterol. IOP Conf Ser: Mater Sci Eng. 2017;172:012035.

    Article  Google Scholar 

  29. Han HJ, Lee JS, Park SA, Ahn JB, Lee HG. Extraction optimization and nanoencapsulation of jujube pulp and seed for enhancing antioxidant activity. Colloids Surf B. 2015;130:93–100.

    Article  CAS  Google Scholar 

  30. Keawchaoon L, Yoksan R. Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles. Colloids Surf B Biointerfaces. 2011;84:163–71.

    Article  CAS  Google Scholar 

  31. Mohammadi A, Hashemi M, Hosseini S. Chitosan nanoparticles loaded with Cinnamomum zeylanicum essential oil enhance the shelf life of cucumber during cold storage. Postharvest Biol Technol. 2015;110:203–13.

    Article  CAS  Google Scholar 

  32. Taşkın D, Doğan M, Ermanoğlu M, Arabaci T. Achillea goniocephala extract loaded into nanochitosan: in vitro cytotoxic and antioxidant activity. Clin Exp Health Sci. 2021;11(4):659–66.

    Google Scholar 

  33. Doğan M, Karademir M. Effect of captopril on the oxidative damage caused by pentylenetetrazole in the SHSY-5Y human neuroblastoma cell line. Cumhuriyet Med J. 2020;42(4):479–83.

    Google Scholar 

  34. Tang H, Zhang Y, Li D, et al. Discovery and synthesis of novel magnolol derivatives with potent anticancer activity in non-small cell lung cancer. Eur J Med Chem. 2018;156:190–205.

    Article  CAS  Google Scholar 

  35. Chen J. Recent advance in the studies of β-glucans for cancer therapy. Anticancer Agents Med Chem. 2013;13:679–80.

    Article  CAS  Google Scholar 

  36. Sachdev E, Tabatabai R, Roy V, Rimel BJ, Mita MM. PARP Inhibition in cancer: An update on clinical development. Target Oncol. 2019;14:657–79.

    Article  Google Scholar 

  37. Sima P, Richter J, Vetvicka V. Glucans as new anticancer agents. Anticancer Res. 2019;39:3373–8.

    Article  CAS  Google Scholar 

  38. Guo C, Li X, Wang R, et al. Association between oxidative DNA damage and risk of colorectal cancer: sensitive determination of urinary 8-hydroxy-2′-deoxyguanosine by UPLC-MS/MS analysis. Sci Rep. 2016;6:1–9. https://doi.org/10.1038/srep32581.

    Article  CAS  Google Scholar 

  39. Chen Z, Zhang B, Gao F, Shi R. Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts. Oncol Lett. 2018;15:1559–65. https://doi.org/10.3892/ol.2017.7475.

    Article  CAS  PubMed  Google Scholar 

  40. Lee SI, Jeong YJ, Yu AR, Kwak HJ, Cha JY, Kang I, Yeo EJ. Carfilzomib enhances cisplatin-induced apoptosis in SK-NBE(2)-M17 human neuroblastoma cells. Sci Rep. 2019;9:1–14.

    Article  Google Scholar 

  41. Filiz AK, Joha Z, Yulak F. Mechanism of anti-cancer effect of β-glucan on SH-SY5Y cell line. Bangladesh J Pharmacol. 2021;16(4):122–8.

    Article  Google Scholar 

Download references

Acknowledgements

This study was performed by own expense in Cumhuriyet University Faculty of Pharmacy Laboratory of Pharmaceutical Biotechnology and Cumhuriyet University Faculty of Medicine Research Center.

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  1. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Murat Dogan

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  1. Murat Dogan
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MD performed experiments and analyzed data. MD supervised the entire project and designed the experiments. MD wrote the paper and read and approved the final manuscript.

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Correspondence to Murat Dogan.

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Dogan, M. Assessment of mechanism involved in the apoptotic and anti-cancer activity of Quercetin and Quercetin-loaded chitosan nanoparticles. Med Oncol 39, 176 (2022). https://doi.org/10.1007/s12032-022-01820-x

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