Skip to main content

Zinc-Phosphate Nanoparticles as a Novel Anticancer Agent: An In Vitro Evaluation of Their Ability to Induce Apoptosis

Biological Trace Element Research volume 198, pages 109–117 (2020)Cite this article

Abstract

In the current study, zinc-phosphate nanoparticles (ZnPNPs) were investigated for the first time due to their anticancer activity against breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line. The modification of such nanoparticles (NPs) was further examined for physicochemical characterization using various techniques such as powder X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential calculation, field emission scanning electron microscopy (FESEM), energy-dispersed spectroscopy (EDS), and Fourier transform infrared (FTIR) spectroscopy. Then, the newly fabricated ZnPNPs were tested for their in vitro cell cytotoxicity against breast cancer MCF-7 cells and noncancerous human embryonic kidney HEK293 cells, using MTT assay as a colorimetric one to assess cell metabolic activity for 24 h. The apoptotic efficacy of the NPs was subsequently confirmed through data obtained from Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining kit and cell cycle analysis. Determination of reactive oxygen species (ROS) generation was further performed via flow cytometry. Additionally, the expression of tumor suppressor genes p53 was analyzed using real-time polymerase chain reaction (PCR). Also, the prepared NPs showed a mean particle size of 38 nm. The measurements correspondingly showed that the cytotoxicity of MCF-7 cells depends on the concentration of NPs (IC50 = 80.112 μg/mL). MCF-7 cells were associated with initiation of apoptotic pathway in cells. Additionally, flow cytometry revealed cell cycle arrest in sub-G1 phase. ROS production was also obtained after treatment with IC50 concentration. According to annexin V-FITC/PI staining kit data, the percentage of early and late apoptotic cells was 78.2% in those treated with ZnPNPs. Moreover, the real-time PCR results demonstrated the ability of NPs in upregulating p53 gene expression. In summary, the data demonstrated that fabricated ZnPNPs had prominence to act as antitumor agents in breast cancer therapy.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

References

  1. Thun MJ, JO DL, Center MM et al (2010) The global burden of cancer: priorities for prevention. Carcinogenesis 31:100–110

    CAS  Article  Google Scholar 

  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  3. Mitra S, Dash R (2018) Natural products for the management and prevention of breast Cancer. Evid Based Complement Alternat Med 2018:8324696. https://doi.org/10.1155/2018/8324696

    Article  PubMed  PubMed Central  Google Scholar 

  4. Palacio J, Agudelo NA, Lopez BL (2016) PEGylation of PLA nanoparticles to improve mucus-penetration and colloidal stability for oral delivery systems. Curr Opin Chem Eng 11:14–19

    Article  Google Scholar 

  5. Singh R, Lillard JW Jr (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86:215–223

    CAS  Article  Google Scholar 

  6. Romagnoli BDAR, Vetere VF, Hernandez LS (1998) Study of the anticorrosive properties of zinc phosphate in vinyl paints. Prog Org Coat 33:28–35

    Article  Google Scholar 

  7. Wang JD, Li D, Liu JK, Yang XH, He JL, Lu Y (2011) One-step preparation and characterization of zinc phosphate Nanocrystals with modified surface soft. Nano Lett 1:81–85

    Google Scholar 

  8. Ghanbar F, Mirzaie A, Ashrafi F, Noorbazargan H, Dalirsaber Jalali M, Salehi S, Shandiz SAS (2017) Antioxidant, antibacterial and anticancer properties of phyto-synthesised Artemisia quttensis Podlech extract mediated AgNPs. IET Nanobiotechnol 11:485–492

    Article  Google Scholar 

  9. Baghbani-Arani F, Movagharnia R, Sharifian A, Salehi S, Shandiz SAS (2017) Photo-catalytic, anti-bacterial, and anti-cancer properties of phyto-mediated synthesis of silver nanoparticles from Artemisia tournefortiana Rchb extract. J Photochem Photobiol Biol 173:640–649

    CAS  Article  Google Scholar 

  10. Jain N, Vergish S, Khurana JP (2018) Validation of house-keeping genes for normalization of gene expression data during diurnal/circadian studies in rice by RT-qPCR. Sci Rep 8:3203

    Article  Google Scholar 

  11. Bigdeli R, Shahnazari M, Panahnejad E, Ahangari Cohan R, Dashbolaghi A, Asgary V (2019) Cytotoxic and apoptotic properties of silver chloride nanoparticles synthesized using Escherichia-coli cell-free supernatant on human breast cancer MCF 7 cell line. Artificial Cells, Nanomed Biotechnol 47:1603–1609

    CAS  Article  Google Scholar 

  12. Du J, Singh H, Yi T-H (2016) Antibacterial, anti-biofilm and anticancer potentials of green synthesized silver nanoparticles using benzoin gum (Styrax benzoin) extract. Bioprocess Biosyst Eng 39:1923–1931

    CAS  Article  Google Scholar 

  13. Foldbjerg R, Olesen P, Hougaard M, Dang DA, Hoffmann HJ, Autrup H (2009) PVP-coated silver nanoparticles and silver ions induce reactive oxygen species, apoptosis and necrosis in THP-1 monocytes. Toxicol Lett 190:156–162

    CAS  Article  Google Scholar 

  14. Asare N, Instanes C, Sandberg WJ, Refsnes M, Schwarze P, Kruszewski M, Brunborg G (2012) Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicol 291:65–72

    CAS  Article  Google Scholar 

  15. Taccola L, Raffa V, Riggio C, Vittorio O, Iorio MC, Vanacore R, Pietrabissa A, Cuschieri A (2011) Zinc oxide nanoparticles as selective killers of proliferating cells. Int J Nanomedicine 6:1129–1140

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Green DR, Walczak H (2013) Apoptotic therapy: driving cancers down the road to ruin. Nat Med 19:131–133

    CAS  Article  Google Scholar 

  17. Whitaker RH, Placzek WJ (2019) Regulating the BCL2 family to improve sensitivity to microtubule targeting agents. Cells 8:346

    CAS  Article  Google Scholar 

  18. George BPA, Kumar N, Abrahamse H, Ray SS (2018) Apoptotic efficacy of multifaceted biosynthesized silver nanoparticles on human adenocarcinoma cells. Sci Rep 8:14368

    Article  Google Scholar 

  19. Li B, Gao Y, Rankin GO, Rojanasakul Y, Cutler SJ, Tu Y, Chen YC (2015) Chaetoglobosin K induces apoptosis and G2 cell cycle arrest through p53-dependent pathway in cisplatin-resistant ovarian cancer cells. Cancer Lett 356:418–433

    CAS  Article  Google Scholar 

  20. Sirelkhatim A, Mahmud S, Seeni A, Kaus NHM (2016) Preferential cytotoxicity of ZnO nanoparticle towards cervical cancer cells induced by ROS-mediated apoptosis and cell cycle arrest for cancer therapy. J Nanopart Res 18:219

    Article  Google Scholar 

  21. Moghaddam AB, Moniri M, Azizi S, Abdul Rahim R, Ariff AB, Navaderi M, Mohamad R (2017) Eco-friendly formulated zinc oxide nanoparticles: induction of cell cycle arrest and apoptosis in the MCF-7 Cancer cell line. Genes (Basel) 8:281

    Article  Google Scholar 

  22. Pati R, Das I, Mehta RK, Sahu R, Sonawane A (2016) Zinc-oxide nanoparticles exhibit genotoxic, clastogenic, cytotoxic and actin depolymerization effects by inducing oxidative stress responses in macrophages and adult mice. Toxicol Sci 150:454–472

    CAS  Article  Google Scholar 

  23. Yang H, Liu C, Yang D, Zhang H, Xi Z (2009) Comparative study of cytotoxicity, oxidative stress and geno-toxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol 29:69–78

    Article  Google Scholar 

  24. Hou J, Wu YZ, Li X, Wei BB, Li SG, Wang XK (2018) Toxic effects of different types of zinc oxide nanoparticles on algae, plants, invertebrates, vertebrates and microorganisms. Chemosphere 193:852–860

    CAS  Article  Google Scholar 

  25. Horky P, Skalickova S, Urbankova L, Baholet D, Kociova S, Bytesnikova Z (2019) Zinc phosphate-based nanoparticles as a novel antibacterial agent: in vivo study on rats after dietary exposure. J Animal Sci Biotechnol 10:17

    Article  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran

    Sedigheh Vafaei, Seyed Ataollah Sadat Shandiz & Zeinab Piravar

Authors
  1. Sedigheh Vafaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seyed Ataollah Sadat Shandiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zeinab Piravar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seyed Ataollah Sadat Shandiz.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vafaei, S., Sadat Shandiz, S.A. & Piravar, Z. Zinc-Phosphate Nanoparticles as a Novel Anticancer Agent: An In Vitro Evaluation of Their Ability to Induce Apoptosis. Biol Trace Elem Res 198, 109–117 (2020). https://doi.org/10.1007/s12011-020-02054-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02054-6

Keywords

  • Zinc-phosphate nanoparticles
  • Apoptosis
  • Cytotoxic
  • MCF-7
  • P53