Skip to main content
Log in

Evaluation of Induced Apoptosis by Biosynthesized Zinc Oxide Nanoparticles in MCF-7 Breast Cancer Cells Using Bak1 and Bclx Expression

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
  • Published:
Doklady Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Zinc oxide nanoparticles (ZnO NPs) have peaked interests in many researches in these recent years due to their advantageous application in modern health care applications. Therefore, we successfully synthesized ZnO NPs by Acacia luciana flower extract as stabilizing, reducing and capping agent, to investigate the antiproliferative potential and apoptosis induction in breast cancer cell lines. The involvements of Acacia luciana bioactive compounds in the stabilization of the ZnO NPs were confirmed by FTIR analysis. FESEM and EDS instruments confirmed that biosynthesized nanoparticles have an irregular morphology and mostly composed of Zn, C, and O respectively. The TEM and zeta potential instruments confirmed that biosynthesized nanoparticles have slight negative charges with particle size of 40 nm. The survivorship of MCF-7 cells were examined by MTT assay and revealed that ZnO NPs inhibited cell viability in a dose- and time-dependent effect with IC50 value of 3.1 µg/mL after 72 h exposure. Also, as a novel work onto ZnO NPs obtained by Acacia extracts, the Bak1/Bclx expression ratio was elucidated utilizing RT-PCR technique. The results demonstrated that ZnO NPs could enhance the expression ratio; therefore they have the potential to induce apoptosis in breast cancer cells via mitochondria-mediated apoptotic pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

Notes

  1. Abbreviations: FESEM, field emission scanning electron microscopy; EDS, energy-dispersive X-ray spectroscopy; TEM, transmission electron microscopy; PCR, polymerase chain reaction; ZnO NPs, zinc oxide nanoparticles.

REFERENCES

  1. Anand, G.T., Renuka, D., Ramesh, R., Anandaraj, L., Sundaram S.J., Ramalingam, G., Magdalane, C.M., Bashir, A., Maaza, M., and Kaviyarasu, K., Green synthesis of ZnO nanoparticle using Prunus dulcis (Almond Gum) for antimicrobial and supercapacitor applications, Surfaces Interfaces, 2019, vol. 17, p. 100376.

    Article  Google Scholar 

  2. Jang, S.J., Yang, I.J., Tettey, C.O., Kim, K.M., and Shin, H.M., In-vitro anticancer activity of green synthesized silver nanoparticles on MCF-7 human breast cancer cells, Mater. Sci. Eng. C, 2016, vol. 68, pp. 430–435.

    Article  CAS  Google Scholar 

  3. Aziz, R.A..A., anak Bronny, B.G., and Alam, S., Zinc oxide nanoparticle synthesis with banana peel extract from jackfruit banana: effects of temperature, Int. J. Technol. Res. Eng., 2019.

  4. Vanaja, M., Paulkumar, K., Baburaja, M., Rajeshkumar, S., Gnanajobitha, G., Malarkodi, C., Sivakavinesan, M., and Annadurai, G., Degradation of methylene blue using biologically synthesized silver nanoparticles, Bioinorg. Chem. Appl., 2014, vol. 2014, no. 1, art. 742346.

  5. Manna, J., Begum, G., Kumar, K.P., Misra, S., and Rana, R.K., Enabling antibacterial coating via bioinspired mineralization of nanostructured ZnO on fabrics under mild conditions, ACS Appl. Mater. Interfaces, 2013, vol. 5, no. 10, pp. 4457–4463.

    Article  CAS  Google Scholar 

  6. Boroumand Moghaddam, A., Moniri, M., Azizi, S., Abdul Rahim, R., Bin Ariff, A., Navaderi, M., and Mohamad, R., Eco-friendly formulated zinc oxide nanoparticles: induction of cell cycle arrest and apoptosis in the MCF-7 cancer cell line, Genes, 2017, vol. 8, no. 10, p. 281.

    Article  Google Scholar 

  7. Sardashti, A.R., Valizadeh, J., and Majd, M.H., Chemical constituents of the flower oil of Acacia luciana from Iran, Int. J. Agricult. Crop Sci., 2015, vol. 8, no. 3, p. 395.

    Google Scholar 

  8. Barsaiya, M. and Singh, D.P., Green synthesis of zinc oxide nanoparticles by Pseudomonas aeruginosa and their broad-spectrum antimicrobial effects, J. Pure Appl. Microbiol., 2018, vol. 12, no. 4, pp. 2123–2134.

    Article  Google Scholar 

  9. Alarifi, S., Ali, H., and Saad Alkahtani, M.S.A., Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage by nano-sized gadolinium oxide, Int. J. Nanomed., 2017, vol. 12, no. 4, p. 541.

    Article  Google Scholar 

  10. Sargazi, A., Barani, A., and Heidari Majd, M., Synthesis and apoptotic efficacy of biosynthesized silver nanoparticles using Аcacia luciana flower extract in MCF-7 breast cancer cells: activation of Bak1 and Bclx for cancer therapy, BioNanoScience, 2020, vol. 10, no. 3, pp. 683–689.

    Article  Google Scholar 

  11. Khan, S.A., Noreen, F., Kanwal, S., Iqbal, A., and Hussain, G., Green synthesis of ZnO and Cu-doped ZnO nanoparticles from leaf extracts of Abutilon indicum, Clerodendrum infortunatum, Clerodendrum inerme, and investigation of their biological and photocatalytic activities, Mater. Sci. Eng. C, 2018, vol. 8, pp. 46–59.

    Article  Google Scholar 

  12. Miri, A., Mahdinejad, N., Ebrahimy, O., Khatami, M., and Sarani, M., Zinc oxide nanoparticles: Biosynthesis, characterization, antifungal and cytotoxic activity, Mater. Sci. Eng. C, 2019, vol. 104, p. 109981.

    Article  CAS  Google Scholar 

  13. Sargazi, A., Kamali, N., Shiri, F., and Heidari Majd, M., Hyaluronic acid/polyethylene glycol nanoparticles for controlled delivery of mitoxantrone, Artificial Cells, Nanomed. Biotechnol., 2018, vol. 46, no. 3, pp. 500–509.

    Article  CAS  Google Scholar 

  14. Mansouri-Torshizi, H., Zareian-Jahromi, S., Gha-hghaei, A., Shahraki, S., Khosravi, F., and Heidari Majd, M., Palladium(II) complexes of biorelevant ligands. Synthesis, structures, cytotoxicity and rich DNA/HSA interaction studies, J. Biomol. Struct. Dynam., 2018, vol. 36, no. 11, pp. 2787–2806.

    Article  CAS  Google Scholar 

  15. Sargazi, A., Azhoogh, M., Allahdad, S., and Heidari Majd, M., Evaluation of supramolecule conjugated magnetic nanoparticles as a simultaneous carrier for methotrexate and tamoxifen, J. Drug Deliv. Sci. Technol., 2018, vol. 47, pp. 115–122.

    Article  CAS  Google Scholar 

  16. Shahraki, S., Shiri, F., Majd, M.H., and Razmara, Z., Comparative study on the anticancer activities and binding properties of a hetero metal binuclear complex [Co(dipic)2Ni(OH2)5] · 2H2O (dipic = dipicolinate) with two carrier proteins, J. Pharm. Biomed. Anal., 2017, vol. 145, pp. 273–282.

    Article  CAS  Google Scholar 

  17. Sargazi, A., Shiri, F., Keikha, S., and Majd, M.H., Hyaluronan magnetic nanoparticle for mitoxantrone delivery toward CD44-positive cancer cells, Colloids Surf. B: Biointerfaces, 2018, vol. 171, pp. 150–158.

    Article  CAS  Google Scholar 

  18. Shahraki, S., Majd, M.H., and Heydari, A., Novel tetradentate Schiff base zinc(II) complex as a potential antioxidant and cancer chemotherapeutic agent: Insights from the photophysical and computational approach, J. Mol. Struct., 2019, vol. 1177, pp. 536–544.

    Article  CAS  Google Scholar 

  19. Barar, J., Kafil, V., Majd, M.H., Barzegari, A., Khani, S., Johari-Ahar, M., Asgari, D., Cokous, G., and Omidi, Y., Multifunctional mitoxantrone-conjugated magnetic nanosystem for targeted therapy of folate receptor-overexpressing malignant cells, J. Nanobiotechnol., 2015, vol. 13, no. 1.

  20. Akhtar, M.J., Ahamed, M., Kumar, S., Khan, M.M., Ahmad, J., and Alrokayan, S.A., Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species, Int. J. Nanomed., 2012, vol. 7, p. 85.

    Google Scholar 

  21. Yip, N., Fombon, I., Liu, P., Brown, S., Kannappan, V., Armesilla, A., Xu, B., Cassidy, J., Darling, J., and Wang, W., Disulfiram modulated ROS–MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties, Br. J. Cancer, 2011, vol. 104, no. 10, p. 1564.

    Article  CAS  Google Scholar 

  22. Alsammarraie, F.K., Wang, W., Zhou, P., Mustapha, A., and Lin, M., Green synthesis of silver nanoparticles using turmeric extracts and investigation of their antibacterial activities, Colloids Surf. B: Biointerfaces, 2018, vol. 171, pp. 398–405.

    Article  CAS  Google Scholar 

  23. Umar, H., Kavaz, D., and Rizaner, N., Biosynthesis of zinc oxide nanoparticles using Albizia lebbeck stem bark, and evaluation of its antimicrobial, antioxidant, and cytotoxic activities on human breast cancer cell lines, Int. J. Nanomed., 2019, vol. 14, p. 87.

    Article  CAS  Google Scholar 

  24. Barsaiya, M. and Singh, D.P., Green synthesis of zinc oxide nanoparticles by Pseudomonas aeruginosa and their broad-spectrum antimicrobial effects, J. Pure Appl. Microbiol., 2018, vol. 12, no. 4, pp. 2123–2134.

    Article  Google Scholar 

  25. Pung, S., Ong, C., Isha, K.M., and Othman, M., Synthesis and characterization of Cu-doped ZnO nanorods, Sains Malaysiana, 2014, vol. 43, no. 2, pp. 273–281.

    CAS  Google Scholar 

  26. Yuan, Y.-G., Zhang, S., Hwang, J.-Y., and Kong, I.-K., Silver nanoparticles potentiates cytotoxicity and apoptotic potential of camptothecin in human cervical cancer cells, Oxid. Med. Cell. Longev., 2018, vol. 2018, art. 6121328. https://doi.org/10.31857/10.1155/2018/6121328

  27. Yuan, Y.-G. and Gurunathan, S., Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells, Int. J. Nanomed., 2017, vol. 12, p. 6537.

    Article  CAS  Google Scholar 

  28. Sirelkhatim, A., Mahmud, S., Seeni, A., Kaus, N.H.M., Ann, L.C., Bakhori, S.K.M., Hasan, H., and Mohamad, D., Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism, Nano-Micro Lett., 2015, vol. 7, no. 3, pp. 219–242.

    Article  CAS  Google Scholar 

  29. Zhang, H., Chen, B., Jiang, H., Wang, C., Wang, H., and Wang, X., A strategy for ZnO nanorod mediated multi-mode cancer treatment, Biomaterials, 2011, vol. 32, no. 7, pp. 1906–1914.

    Article  CAS  Google Scholar 

  30. Jeng, H.A. and Swanson, J., Toxicity of metal oxide nanoparticles in mammalian cells, J. Environ. Sci. Health A, 2006, vol. 41, no. 12, pp. 2699–2711.

    Article  CAS  Google Scholar 

  31. Souza, R.C.D., Haberbeck, L.U., Riella, H.G., Ribeiro, D.H., and Carciofi, B.A., Antibacterial activity of zinc oxide nanoparticles synthesized by solochemical process, Braz. J. Chem. Eng., 2019, vol. 36, no. 2, pp. 885–893.

    Article  Google Scholar 

  32. Shobha, N., Nanda, N., Giresha, A.S., Manjappa, P., Sophiya, P., Dharmappa, K., and Nagabhushana, B., Synthesis and characterization of Zinc oxide nanoparticles utilizing seed source of Ricinus communis and study of its antioxidant, antifungal and anticancer activity, Mater. Sci. Eng. C, 2019, vol. 97, pp. 842–850.

    Article  CAS  Google Scholar 

  33. Sukri, S.N.A.M., Shameli, K., Wong, M.M.-T., Teow, S.-Y., Chew, J., and Ismail, N.A., Cytotoxicity and antibacterial activities of plant-mediated synthesized zinc oxide (ZnO) nanoparticles using Punica granatum (pomegranate) fruit peels extract, J. Mol. Struct., 2019, vol. 1189, pp. 57–65.

    Article  Google Scholar 

  34. El-Shorbagy, H.M., Eissa, S.M., Sabet, S., and El-Ghor, A.A., Apoptosis and oxidative stress as relevant mechanisms of antitumor activity and genotoxicity of ZnO-NPs alone and in combination with N-acetyl cysteine in tumor-bearing mice, Int. J. Nanomed., 2019, vol. 14, p. 3911.

    Article  CAS  Google Scholar 

  35. Wang, L., Chen, C., Guo, L., Li, Q., Ding, H., Bi, H., and Guo, D., Zinc oxide nanoparticles induce murine photoreceptor cell death via mitochondria-related signaling pathway, Artificial Cells, Nanomed., Biotechnol., 2018, vol. 46, supl. 1, pp. 1102–1113.

    Article  Google Scholar 

  36. Sun, L., Yuan, Q., Xu, T., Yao, L., Feng, J., Ma, J., Wang, L., Lu, C., and Wang, D., Pioglitazone improves mitochondrial function in the remnant kidney and protects against renal fibrosis in 5/6 nephrectomized rats, Front. Pharmacol., 2017, vol. 8, p. 545.

    Article  Google Scholar 

  37. Susnow, N., Zeng, L., Margineantu, D., and Hockenbery, D.M., Bcl-2 family proteins as regulators of oxidative stress, Semin. Cancer Biol., 2009, pp. 42–49.

  38. Bauer, C., Hees, C., Sterzik, A., Bauernfeind, F., Mak’Anyengo, R., Duewell, P., Lehr, H.-A., Noess-ner, E., Wank, R., and Trauzold, A., Proapoptotic and antiapoptotic proteins of the Bcl-2 family regulate sensitivity of pancreatic cancer cells toward gemcitabine and T-cell–mediated cytotoxicity, J. Immunother., 2015, vol. 38, no. 3, pp. 116–126.

    Article  CAS  Google Scholar 

  39. Bai, D.-P., Zhang, X.-F., Zhang, G.-L., Huang, Y.-F., and Gurunathan, S., Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells, Int. J. Nanomed., 2017, vol. 12, p. 6521.

    Article  CAS  Google Scholar 

  40. Meyer, K., Rajanahalli, P., Ahamed, M., Rowe, J.J., and Hong, Y., ZnO nanoparticles induce apoptosis in human dermal fibroblasts via p53 and p38 pathways, Toxicol. In Vitro, 2011, vol. 25, no. 8, pp. 1721–1726.

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors thank the Deputy of Research and Technology of Zabol University of Medical Sciences for all support provided.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mostafa Heidari Majd.

Ethics declarations

The authors declare that they have no conflict of interest.

This study was approved by the ethical committee of Zabol University of Medical Sciences (IR.ZBMU.REC.1398.088). There is no duplicate publication, fraud, plagiarism, or concerns about animal or human experimentation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yan, M., Majd, M.H. Evaluation of Induced Apoptosis by Biosynthesized Zinc Oxide Nanoparticles in MCF-7 Breast Cancer Cells Using Bak1 and Bclx Expression. Dokl Biochem Biophys 500, 360–367 (2021). https://doi.org/10.1134/S1607672921050148

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1607672921050148

Keywords:

Navigation