Investigating the Anticancer Properties of Zinc Oxide Nanoparticles Conjugated with Thiosemicarbazide on Gastric Cancer Cells and Evaluation the Expression Level of CASP8 and HULC Genes

Beigi, Sadaf; Salehzadeh, Ali; Habibollahi, Hadi; Sadat Shandiz, Seyed Ataollah; Safa, Fariba

[Home ] [Archive]

[ فارسی ]

Journal of Ilam University of Medical Sciences

Main Menu

Home

Journal Information

Articles archive

Publication Ethics

Peer Review Process

Indexing Databases

For Authors

For Reviewers

Subscription

Contact us

Site Facilities

Google Scholar Metrics

	All	Since 2020
Citations	6809	3459
h-index	27	19
i10-index	196	77

Search in website

Receive site information

Registered in

Volume 32, Issue 6 (2-2025)

Journal of Ilam University of Medical Sciences 2025, 32(6): 109-127

Back to browse issues page

Investigating the Anticancer Properties of Zinc Oxide Nanoparticles Conjugated with Thiosemicarbazide on Gastric Cancer Cells and Evaluation the Expression Level of CASP8 and HULC Genes

Sadaf Beigi¹

, Ali Salehzadeh ^*

², Hadi Habibollahi¹

, Seyed Ataollah Sadat Shandiz³

, Fariba Safa⁴

1- Dept of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran
2- Dept of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran , salehzadehmb@yahoo.com
3- Dept of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
4- Dept of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran

Abstract: (282 Views)

Introduction: Nanotechnology The invention has significantly enhanced the treatment of stomach cancer. Thiosemicarbazones, a novel class of medicines that can be complexed with nanoparticles. Thus, the aim of this study was to synthesize zinc oxide nanoparticles functionalized with glutamine and conjugated with thiosmecarbazone and their cytotoxicity and their effect on the expression of CASP8 and HULC Lnc-RNA genes.
Materials & Methods: In this experimental study, zinc oxide (ZnO) nanoparticles were first synthesized and functionalized with glutamine (ZnO@Gln) and conjugated with thiosimicarbazide (ZnO@Gln-TSC). FTIR, XRD, DLS, SEM, TEM analyses were performed to investigate the synthesis of nanoparticles. The cytotoxicity of nanoparticles on AGS cells was investigated by MTT test under different concentrations. The expression level of CASP8 and HULC genes under the influence of IC50 concentration of nanoparticles were investigated by the real-time PCR method. Data analysis was conducted using SPSS Version 16, using ANOVA and T-tests, with a P-value threshold of less than 0.05 deemed significant.
Results: FT-IR and XRD tests confirmed what the particles were made of, and the nanoparticles were found to be between 30 and 70 nm in size. DLS showed the size of nanoparticles to be 296 nm. The MTT test showed that the IC50 value of nanoparticles was 10 µg/mL. Nanoparticles turned AGS cells into a test group where the CASP8 gene went up by 6.79 and the HULC gene went down by 0.65 compared to the control group (P < 0.05).
Conclusion: Nanoparticles of ZnO@Gln-TSC had an effect on AGS cancer cells by increasing the amount of CASP8 and decreasing the expression of the HULC gene. This stopped cell growth and caused apoptosis, which could be further studied as a drug for treating cancer.

Keywords: Thiosimicarbazide, Gastric Cancer, Nanoparticles zinc oxide, CASP3, HULC

Full-Text [PDF 1439 kb] (102 Downloads)

Type of Study: Research | Subject: biology
Received: 2024/05/11 | Accepted: 2024/07/24 | Published: 2025/02/3

References

1. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. The Lancet. 2020; Aug 29;396(10251):635-648. doi: 10.1016/S0140-6736(20)31288-5.

2. 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 CA: a cancer journal for clinicians. 2018; Nov;68(6):394-424. doi: 10.3322/caac.21492.

3. Wydra RJ, Oliver CE, Anderson KW, Dziubla TD, Hilt JZ. Accelerated generation of free radicals by iron oxide nanoparticles in the presence of an alternating magnetic field. RSC Adv RSC advances. 2015;;5(24):18888-18893. doi: 10.1039/C4RA13564D. [DOI:10.1039/C4RA13564D]

4. Mokwena MG, Kruger CA, Ivan MT, Heidi A. A review of nanoparticle photosensitizer drug delivery uptake systems for photodynamic treatment of lung cancer. Photodiagnosis Photodyn Ther Photodiagnosis and photodynamic therapy.2018; Jun 1;22:147-54. doi: 10.1016/j.pdpdt.2018.03.006.

5. Jayarambabu N, Kumari BS, Rao KV, Prabhu YT. Beneficial role of zinc oxide nanoparticles on green crop production. Int J Multidiscip Adv. Res. Trends. 2015;;2(1):273-82.

6. Han N, Xu L, Zheng H, Yang Y, Fan W. In vivo co-delivery of paclitaxel and herceptin for Her2/Neu+ breast cancer treatment using micellar nanoparticles. Nanomed: Nanotechnol Biol MedNanomedicine: Nanotechnology, Biology and Medicine. 2016; 2(12):513-4. doi: 10.1016/j.nano.2015.12.191.

7. Altman BJ, Stine ZE, Dang CV. From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev CancerNature Reviews Cancer. 2016; Oct;16(10): 619-34. doi: 10.1038/nrc.2016.71.

8. Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: metabolism and immune function, supplementation and clinical translation. Nutrients. 2018; Oct 23;10(11):1564. doi: 10.3390/nu10111564.

9. Pelosi G. Thiosemicarbazone metal complexes: from structure to activity. The Open CrystallogrCrystallography Journal. 2010; Mar 25;3: 16-28. doi: 10.2174/1874846501003010016.

10. Sadat Shandiz SA, Montazeri A, Abdolhosseini M, Hadad Shahrestani S, Hedayati M, Moradi-Shoeili Z, Salehzadeh Aet al. Functionalization of Ag nanoparticles by glutamic acid and conjugation of Ag@ Glu by thiosemicarbazide enhances the apoptosis of human breast cancer MCF-7 cells. J Clust SciJournal of Cluster Science. 2018;29 Nov;29:1107-14. doi:10.1007/s10876-018-1424-0.

11. Ma ZY, Shao J, Bao WG, Qiang ZY, Xu JY. A thiosemicarbazone copper (II) complex as a potential anticancer agent. Journal of Coordination Chemistry. 2015; Jan 17;68(2): 277-94. doi:10.1080/00958972.2014.979811.

12. Paul-Samojedny M, Kokocińska D, Samojedny A, Mazurek U, Partyka R, Lorenz Z, et al. Expression of cell survival/death genes: Bcl-2 and Bax at the rate of colon cancer prognosis. Biochim Biophys Acta Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease.2005; Jun 30;1741(1-2):25-29. doi: 10.1016/j.bbadis.2004.11.021.

13. Rofeal M, El-Malek FA. Valorization of lipopeptides biosurfactants as anticancer agents. Int J Pept Res TherInternational Journal of Peptide Research and Therapeutics. 2021; Mar;27:447-55. doi:10.1007/s10989-020-10105-8.

14. Peng W, Gao W, Feng J. Long noncoding RNA HULC is a novel biomarker of poor prognosis in patients with pancreatic cancer. Clin OncolMedical oncology. 2014; Dec;31:1-7. doi: 10.1007/s12032-014-0346-4.

15. Gonzalez I, Munita R, Agirre E, Dittmer TA, Gysling K, Misteli T, Luco RFet al. A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nat Struct Mol BiolNature structural & molecular biology. 2015; May;22(5):370-6. doi: 10.1038/nsmb.3005.

16. Zhao Y, Guo Q, Chen J, Hu J, Wang S, Sun Y. Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: a clinical and in vitro investigation. Oncol Rep 2014; Jan 1;31(1):358-64. doi:10.3892/or.2013.2850.

17. Nejabatdoust A, Salehzadeh A, Zamani H, Moradi-Shoeili Z. Synthesis, characterization and functionalization of ZnO nanoparticles by glutamic acid (Glu) and conjugation of ZnO@ Glu by thiosemicarbazide and its synergistic activity with ciprofloxacin against multi-drug resistant Staphylococcus aureus. J Clust SciJournal of Cluster Science. 2019; Mar 15;30:329-36. doi:10.1007/s10876-018-01487-3.

18. Taati H, Sangani H, Davoudi A, Safabakhsh Kouchesfahani S, Hedayati M, et al. Silver nanoparticle functionalized by glutamine and conjugated with thiosemicarbazide induces apoptosis in colon cancer cell line. Sci Rep 2024; 14:3809. Taati, H., Sangani, H., Davoudi, A., Safabakhsh Kouchesfahani, S., Hedayati, M., Tarashandeh Hemmati, S., Ghasemipour, T., Aghajani, S., Farah Andooz, M., Amanollahi, M. and Kalavari, F., 2024. Silver nanoparticle functionalized by glutamine and conjugated with thiosemicarbazide induces apoptosis in colon cancer cell line. Scientific Reports, 14(1), p.3809. doi: 10.1038/s41598-024-54344-x. Ramesh P, Saravanan K, Manogar P, Johnson J, Vinoth E, Mayakannan Met al. Green synthesis and characterization of biocompatible zinc oxide nanoparticles and evaluation of its antibacterial potential. Sens Bio Sens Res Sensing and Bio-Sensing Research. 2021; Feb 1;31:100399. doi: 10.1016/j.sbsr.2021.100399.

19. Senthilkumar SR, Sivakumar T. Green tea (Camellia sinensis) mediated synthesis of zinc oxide (ZnO) nanoparticles and studies on their antimicrobial activities. Int. J. Pharm.. Sci. 2014; Jun 6;6(6): 461-5.

20. Pawlukojć A, Hołderna-Natkaniec K, Bator G, Natkaniec I. L-glutamine: Dynamical properties investigation by means of INS, IR, RAMAN, 1H NMR and DFT techniques. Chem Phys Chemical physics. 2014; Oct 31;443:17-25. doi: 10.1016/j.chemphys.2014.08.003.

21. Khurana N, Arora P, Pente AS, Pancholi KC, Kumar V, Kaushik CP, Rattan Set al. Surface modification of zinc oxide nanoparticles by vinyltriethoxy silane (VTES). Inorg Chem Commun Inorganic Chemistry Communications. 2021; Feb 1;124:108347. doi: 10.1016/j.inoche.2020.108347.

22. Barrak H, Saied T, Chevallier P, Laroche G, M’nif A, Hamzaoui AH. Synthesis, characterization, and functionalization of ZnO nanoparticles by N-(trimethoxysilylpropyl) ethylenediamine triacetic acid (TMSEDTA): Investigation of the interactions between Phloroglucinol and ZnO@ TMSEDTA. Arab J ChemArabian Journal of Chemistry. 2019; Dec 1;12(8):4340-7. doi: 10.1016/j.arabjc.2016.04.019.

23. Dehkaei AA, Khalatbari K, Emamifar A, Taramsari SM, Balkhi S, Ghezeljeh SM, Gorji S, Gholipoor S, Noveiri MJ, Hedayati M, Salehzadeh Aet al. Cytotoxicity effect of nickel hydroxide nanoparticles functionalized by glutamine and conjugated by thiosemicarbazide on human lung cancer cell line (A549) and evaluation of bax and bcl-2 genes expression. Gene Reports. 2022; Dec 1;29:101700. doi: 10.1016/j.genrep.2022.101700.

24. Jamdagni P, Khatri P, Rana JS. Green synthesis of zinc oxide nanoparticles using flower extract of Nyctanthes arbor-tristis and their antifungal activity. J King Saud Univ SciJournal of King Saud University-Science. 2018; Apr 1;30(2):168-75. doi: 10.1016/j.jksus.2016.10.002.

25. Wang MS, Chen L, Xiong YQ, Xu J, Wang JP, Meng ZLet al. Iron oxide magnetic nanoparticles combined with actein suppress non-small-cell lung cancer growth in a p53-dependent manner. Int J NanomedicineInternational Journal of Nanomedicine. 2017; Oct 17:7627-51. doi: 10.2147/IJN.S127549.

26. Akhtar MJ, Ahamed M, Kumar S, Khan MM, Ahmad J, Alrokayan Saet al. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int J Nanomedicine International journal of nanomedicine. 2012; Feb 21:845-57. doi: 10.2147/IJN.S29129.

27. Pandurangan M, Enkhtaivan G, Kim DH. Anticancer studies of synthesized ZnO nanoparticles against human cervical carcinoma cells. J Photochem Photobiol BJournal of Photochemistry and Photobiology B: Biology. 2016; May 1;158:206-11. doi: 10.1016/j.jphotobiol.2016.03.002.

28. Antonio J, Street C. Glutamine: a potentially useful supplement for athletes. Can J Appl PhysiolCanadian Journal of Applied Physiology. 1999; Feb 1;24:1-4. doi: 10.1139/h99-001.

29. Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin InvestThe Journal of clinical investigation. 2013; Sep 3;123(9):3678-84. doi: 10.1172/JCI69600.

30. Hamrayev H, Shameli K, Yusefi M. Preparation of zinc oxide nanoparticles and its cancer treatment effects: A review paper. Journal of Advanced Research in Micro and Nano Engineering. 2020;;2(1):1-1.

31. Ma ZY, Shao J, Bao WG, Qiang ZY, Xu JY. A thiosemicarbazone copper (II) complex as a potential anticancer agent. Journal of Coordination Chemistry. 2015; Jan 17;68(2): 277-94. Doi:10.1080/00958972.2014.979811.

32. Yildirim H, Guler E, Yavuz M, Ozturk N, Yaman PK, Subasi E, Sahin E, Timur Set al. Ruthenium (II) complexes of thiosemicarbazone: Synthesis, biosensor applications and evaluation as antimicrobial agents. Mater Sci Eng C Mater Biol Appl 2014; Nov 1;44:1-8. doi: 10.1016/j.msec.2014.08.007.

33. Gou Y, Wang J, Chen S, Zhang Z, Zhang Y, Zhang W, Yang Fet al. α− N− heterocyclic thiosemicarbazone Fe (III) complex: Characterization of its antitumor activity and identification of anticancer mechanism. Eur J Med ChemEuropean Journal of Medicinal Chemistry. 2016; Nov 10;123:354-64. doi: 10.1016/j.ejmech.2016.07.041.

34. Goya GF, Grazu V, Ibarra MR. Magnetic nanoparticles for cancer therapy. Curr NanosciCurrent nanoscience. 2008; Feb 1;4(1):1-6. doi:10.2174/157341308783591861.

35. Jarestan M, Khalatbari K, Pouraei A, Sadat Shandiz SA, Beigi S, Hedayati M, Majlesi A, Akbari F, Salehzadeh Aet al. Preparation, characterization, and anticancer efficacy of novel cobalt oxide nanoparticles conjugated with thiosemicarbazide. 3 Biotech. 2020; May;10:1-9. doi: 10.1007/s13205-020-02230-4.

36. Habibzadeh SZ, Salehzadeh A, Moradi-Shoeili Z, Shandiz SA. A novel bioactive nanoparticle synthesized by conjugation of 3-chloropropyl trimethoxy silane functionalized Fe3O4 and 1-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl) methylene)-2-(4-phenylthiazol-2-yl) hydrazine: assessment on anti-cancer against gastric AGS cancer cells. Molecular Biology Reports. 2020; Mar;47(3):1637-47. doi:10.1007/s11033-020-05251-7.

37. Hosseinkhah M, Ghasemian R, Shokrollahi F, Mojdehi SR, Noveiri MJ, Hedayati M, Rezaei M, Salehzadeh Aet al. Cytotoxic potential of nickel oxide nanoparticles functionalized with glutamic acid and conjugated with thiosemicarbazide (NiO@ Glu/TSC) against human gastric cancer cells. J Clust SciJournal of Cluster Science. 2022; Sep;33(5):2045-53. doi:10.1007/s10876-021-02124-2.

38. Badrooh M, Shokrollahi F, Javan S, Ghasemipour T, Rezaei Mojdehi S, Farahnak H, Jahani Sayyad Noveiri M, Hedayati M, Salehzadeh Aet al. Trigger of apoptosis in adenocarcinoma gastric cell line (AGS) by a complex of thiosemicarbazone and copper nanoparticles. Molecular Biology Reports. 2022; Jan 49:2217-26. doi: 10.1007/s11033-021-07043-z.

39. Dong Y, Wei MH, Lu JG, Bi CY. Long non-coding RNA HULC interacts with miR-613 to regulate colon cancer growth and metastasis through targeting RTKN. Biomed PharmacotherBiomedicine & pharmacotherapy= Biomedecine & pharmacotherapie. 2018; Nov 26;109:2035-42. doi: 10.1016/j.biopha.2023.115370.

40. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nature Reviews Cancer. 2006; Apr 1;6(4):259-69. doi:10.1038/nrc1840.

Send email to the article author

Add your comments about this article

Ethics code: مطالعه بر روی انسان نبوده است

Mendeley

Zotero

RefWorks

Beigi S, Salehzadeh A, Habibollahi H, Sadat Shandiz S A, Safa F. Investigating the Anticancer Properties of Zinc Oxide Nanoparticles Conjugated with Thiosemicarbazide on Gastric Cancer Cells and Evaluation the Expression Level of CASP8 and HULC Genes. J. Ilam Uni. Med. Sci. 2025; 32 (6) :109-127
URL: http://sjimu.medilam.ac.ir/article-1-8285-en.html

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

Volume 32, Issue 6 (2-2025)

Back to browse issues page

Persian site map - English site map - Created in 0.16 seconds with 41 queries by YEKTAWEB 4680