The effect of copper oxide nanoparticle conjugated with lapatinib on breast cancer cell line and evaluating the effect of this nanoparticle on caspase 8 gene expression

Valizadeh Talarposhti, Masoumeh; Salehzadeh, Ali; Jalali, Amir

[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	6898	3526
h-index	29	19
i10-index	199	78

Search in website

Receive site information

Registered in

Volume 33, Issue 1 (4-2025)

Journal of Ilam University of Medical Sciences 2025, 33(1): 55-70

Back to browse issues page

The effect of copper oxide nanoparticle conjugated with lapatinib on breast cancer cell line and evaluating the effect of this nanoparticle on caspase 8 gene expression

Masoumeh Valizadeh Talarposhti¹

, Ali Salehzadeh ^*²

, Amir Jalali³

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, Faculty of Science, Arak University, Arak, Iran

Abstract: (123 Views)

Introduction: Breast cancer is a significant global cause of cancer-related mortality, highlighting the urgent need for new drugs to combat this prevalent disease. This study was designed to investigate the anticancer effect of copper oxide nanoparticles conjugated with lapatinib and its effect on the expression of the caspase-8 gene in a breast cancer cell line.
Materials & Methods: Copper oxide nanoparticles were synthesized from a CuCl₂ solution, treated with D-glucose, and then linked to lapatinib. The physicochemical properties of the nanoparticles were analyzed using FT-IR, XRD, EDS, DLS, zeta potential measurement, and electron microscope imaging. The effect of the nanoparticles on the viability of breast cancer (MDA-MB-231) and normal (MRC-5) cells was evaluated using the MTT test, while the expression of the caspase-8 gene was measured via real-time PCR. Statistical differences were analyzed using one-way ANOVA in SPSS V.22, with a p-value less than 0.05 considered statistically significant.
Results: The study found that copper oxide nanoparticles conjugated with lapatinib had a spherical morphology, a surface charge of -14 mV, and a particle size of 426.3 nm in aqueous medium. These nanoparticles had concentration-dependent inhibitory effects on cancer and normal cell lines, with a 50% inhibitory concentration of 75 and 120 μg/ml, respectively, and a 3.24-fold increase in caspase-8 gene expression.
Conclusion: Copper oxide nanoparticles linked with lapatinib were more effective at stopping cancer cells than normal cells, and by boosting the levels of caspase-8, they trigger the external pathway of cell death in cancer cells.

Keywords: Apoptosis, Breast Cancer, Copper Oxide Nanoparticle, Lapatinib

Full-Text [PDF 1381 kb] (41 Downloads)

Type of Study: Research | Subject: biology
Received: 2024/08/9 | Accepted: 2025/01/18 | Published: 2025/04/16

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71:209-49 doi: 10.3322/caac.21660.

2. Fang X, Cao J, Shen A. Advances in anti-breast cancer drugs and the application of nano-drug delivery systems in breast cancer therapy. J Drug Deliv Sci Technol. 2020;57:101662. doi:10.1016/j.jddst.2020.101662.

3. Kim GJ, Nie S. Targeted cancer nanotherapy. Mater Today. 2005; 8:28-33. doi:10.1016/S1369-7021(05)71034-8.

4. Waris A, Din M, Ali A, Ali M, Afridi S, Baset A, et al. A comprehensive review of green synthesis of copper oxide nanoparticles and their diverse biomedical applications. Inorg Chem Commun. 2021; 123:108369. doi:10.1016/j.inoche.2020.108369.

5. Verma N, Kumar N. Synthesis and biomedical applications of copper oxide nanoparticles: an expanding horizon. Verma N, Kumar N. Synthesis and biomedical applications of copper oxide nanoparticles: an expanding horizon. ACS Biomater Sci Eng. 2019; 5:1170-88. doi:10.1021/acsbiomaterials.8b01092.

6. Szymański P, Frączek T, Markowicz M, Mikiciuk-Olasik E. Development of copper based drugs, radiopharmaceuticals and medical materials. Biometals. 2012; 25:1089-112. doi:10.1007/s10534-012-9578-y.

7. Chandrakala V, Aruna V, Angajala G. Review on metal nanoparticles as nanocarriers: Current challenges and perspectives in drug delivery systems. Emerg Mater. 2022; 5:1593-615. doi:10.1007/s1001841722004867.

8. Rahnama A, Gharagozlou M. Preparation and properties of semiconductor CuO nanoparticles via a simple precipitation method at different reaction temperatures. Opt Quantum Electron. 2012; 44:313-22. doi:10.1007/s11082-011-9540-1.

9. Hosseinkhah M, Ghasemian R, Shokrollahi F, Mojdehi SR, Noveiri MJ, Hedayati M, et 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 Sci. 2022; 33:2045-53. doi:10.1007/s10876-021-02124-2.

10. Kumari R, Saini AK, Kumar A, Saini RV. Apoptosis induction in lung and prostate cancer cells through silver nanoparticles synthesized from Pinus roxburghii bioactive fraction. J Biol Inorg Chem. 2020; 25:23-37. doi: 10.1007/s00775-019-01729-3.

11. Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res. 2001; 29:e45. doi: 10.1093/nar/29.9. e45.

12. Talarposhti MV, Salehzadeh A, Jalali A. Comparing the toxicity effects of copper oxide nanoparticles conjugated with Lapatinib on breast (MDA-MB-231) and lung (A549) cancer cell lines. Naunyn Schmiedebergs Arch Pharmacol. 2024: 397 :6855-6866. doi: 10.1007/s00210-024-03071-1.

13. Bouazizi N, Bargougui R, Oueslati A, Benslama R. Effect of synthesis time on structural, optical and electrical properties of CuO nanoparticles synthesized by reflux condensation method. Adv Mater Lett. 2015; 6:158-64. doi: 10.5185/amlett.2015.5656.

14. Varlashkin P. X-ray powder diffraction data of lapatinib ditosylate monohydrate. Powder Diffr. 2009; 24:250-3. doi:10.1154/1.3187152.

15. Yang Q, Wang YE, Yang Q, Gao Y, Duan X, Fu Q, et al. Cuprous oxide nanoparticles trigger ER stress-induced apoptosis by regulating copper trafficking and overcoming resistance to sunitinib therapy in renal cancer. Biomaterials. 2017; 146:72-85. doi:10.1016/j.biomaterials.2017.09.008.

16. Zughaibi TA, Mirza AA, Suhail M, Jabir NR, Zaidi SK, Wasi S, et al. Evaluation of anticancer potential of biogenic copper oxide nanoparticles (CuO NPs) against breast cancer. J Nanomater. 2022;2022:5326355. doi:10.1155/2022/5326355.

17. Shafiei I, Tavassoli SP, Rahmatollahi HR, Ghasemian R, Salehzadeh A. A novel copper oxide nanoparticle conjugated by thiosemicarbazone promote apoptosis in human breast cancer Cell line. J Clust Sci. 2022;33:2697-706. doi:10.1007/s10876-021-02187-1.

18. Segovia-Mendoza M, González-González ME, Barrera D, Díaz L, García-Becerra R. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: preclinical and clinical evidence. Am J Cancer Res. 2015;5:2531.

19. Xuhong JC, Qi XW, Zhang Y, Jiang J. Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer. Am J Cancer Res. 2019; 9:2103-19.

20. Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016; 1863:2977-92. doi: 10.1016/j.bbamcr.2016.09.012.

21. Mandal R, Barrón JC, Kostova I, Becker S, Strebhardt K. Caspase-8: The double-edged sword. Biochim Biophys Acta Rev Cancer. 2020; 1873:188357. doi: 10.1016/j.bbcan.2020.188357.

22. Mahmood RI, Kadhim AA, Ibraheem S, Albukhaty S, Mohammed-Salih HS, Abbas RH, et al. Biosynthesis of copper oxide nanoparticles mediated Annona muricata as cytotoxic and apoptosis inducer factor in breast cancer cell lines. Sci Rep. 2022; 12: 16165. doi:10.1038/s41598-022-20360-y.

23. Li YT, Qian XJ, Yu Y, Li ZH, Wu RY, Ji J, et al. EGFR tyrosine kinase inhibitors promote pro-caspase-8 dimerization that sensitizes cancer cells to DNA-damaging therapy. Oncotarget. 2015;6:17491. doi: 10.18632/oncotarget.3959.

24. Tajmehri H, Mousavi FS, heydarnezhad M, Golrokh FJ, Nezami PV, Khanpour P, et al. Evaluation of the cytotoxic effect of cobalt oxide nanoparticles functionalized by glucose and conjugated with lapatinib (Co3O4@ Glu-Lapatinib) on a lung cancer cell line and evaluation of the expression of CASP8, mTOR1, and MAPK1 genes. BioNanoScience. 2024;14:999-1010. doi:10.1007/s12668-024-01348-6.

Send email to the article author

Add your comments about this article

Ethics code: نیاز به کد اخلاق نبوده است.

Mendeley

Zotero

RefWorks

Valizadeh Talarposhti M, Salehzadeh A, Jalali A. The effect of copper oxide nanoparticle conjugated with lapatinib on breast cancer cell line and evaluating the effect of this nanoparticle on caspase 8 gene expression. J. Ilam Uni. Med. Sci. 2025; 33 (1) :55-70
URL: http://sjimu.medilam.ac.ir/article-1-8352-en.html

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

Volume 33, Issue 1 (4-2025)

Back to browse issues page

Persian site map - English site map - Created in 0.15 seconds with 39 queries by YEKTAWEB 4701