Evaluation of Cytotoxic and Apoptotic Effects of Green Synthesized Zn Oxide Nanoparticles on the MCF-7 breast cancer Cell Line

authors:

avatar Parisa Shishesaz , avatar Masoumeh Mahdavi , avatar Fatemeh Ghodratpour , avatar fahimeh baghbani-arani , *


how to cite: Shishesaz P, Mahdavi M, Ghodratpour F, baghbani-arani F. Evaluation of Cytotoxic and Apoptotic Effects of Green Synthesized Zn Oxide Nanoparticles on the MCF-7 breast cancer Cell Line. koomesh. 2023;25(2):e152825. 

Abstract

Introduction: Today, nanoparticles have been considered an effective anti-cancer factor in cancer therapy and diagnostic studies. In this way, nanoparticles synthesized by biological methods are being developed. This study aimed to green synthesize zinc oxide nanoparticles by Bunium persicum and study toxicity and apoptotic effects in breast cancer cell lines. Materials and Methods: Zinc oxide nanoparticles were synthesized by the fruit extract of Bunium persicum and synthesized nanoparticles were evaluated by FESEM, EDS, XRD, and Zeta sizer analyses. Then, the cytotoxicity of ZnO nanoparticles on breast cancer cell line MCF-7 and normal HEK-293 was evaluated by the MTT method within 24 hours, and the IC50 lethality was determined. Finally, P53, Bcl2, and Bax gene expression were analyzed by Real-time PCR. Results: ZnO nanoparticles with an average size of 100 nm and a polyhedral shape were made using the fruit extract of the Bunium persicum. According to the XRD analysis, the synthesized nanoparticles have a single-phase crystal structure and no impurities. Based on the MTT results, ZnO nanoparticles had cytotoxicity effects on cancer cells (in 16-500 µg/ml concentration) as well as normal HEK-293 cells (in 31-500 µg/ml concentration) (P<0.001). The gene expression results indicated a 2.7-fold increase in P53 (P<0.001), 6.2 in Bax, and 2.3-fold in Bcl2  (P<0.001). Conclusion: The findings indicated that the fabrication of zinc oxide nanoparticles by fruit extract of Bunium persicum was done successfully. Also, these nanoparticles have toxicity effects on breast cancer cell lines, and this toxicity is probably due to the induction of apoptosis.

References

  • 1.

    Anastasiadi Z, Lianos GD, Ignatiadou E, Harissis HV, Mitsis M. Breast cancer in young woman: anoverview. Update Surg 2017; 69: 313-317.

  • 2.

    Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin 2016; 66: 7-30.

  • 3.

    Jiang H, Moon Ks, Li Y, Wong CP. Surface functionalized silver nanoparticles for ultrahigh conductive polymer composites. Chem Mater 2006; 18: 2969-2973.##https://doi.org/10.1021/cm0527773.

  • 4.

    Djurii AB, Leung YH, Ng AM, Xu XY, Lee PK, Degger N, et al. Toxicity of metal oxide nanoparticles: mechanisms, characterization, and avoiding experimental artefacts. Small 2015; 11: 26-44.

  • 5.

    Sharma H, Mishra Pk, Talegaonkar S, Vaidya B. Metal nanoparticles: a theranostic nanotool against cancer. Drug Discov 2015; 20: 1143-1151.

  • 6.

    Wahab R, Dwivedi S, Umar A, Singh S, Hwang IH, Shin HS, et al. ZnO nanoparticles induce oxidative stress in cloudman S91 melanoma cancer cells. J Biomed Nanotechnol 2013; 9: 441-449.

  • 7.

    Akhtar MJ, Ahamed M, Kumar S, Khan MM, Ahmad J, Alrokayan SA. Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species. Int J Nanomedicine 2012; 7: 845-857.

  • 8.

    Surbone A, T ralongo P. Categorization of cancer survivors: why we need it. J Clin Oncol 2016; 34: 3372-3374.

  • 9.

    Rafiee B, Ghani S, Sadeghi D, Ahsani M. Green synthesis of zinc oxide nanoparticles using eucalyptus mellidora leaf extract and evaluation of its antimicrobal effects. J Babol Univ Med Sci 2018; 20: 28-35. (Persian).

  • 10.

    Gharbavi M, Johari M, Ghorbani R, Madanchi H, Sharafi A. Green synthesis of Zn nanoparticles and in situ hybridized with BSA nanoparticles for Baicalein targeted delivery mediated with glutamate receptors to U87-MG cancer cell lines. Appl Organomet Chem 2023; 37: e6926.##https://doi.org/10.1002/aoc.6926.

  • 11.

    Haghirossadat F, Bernard F, Kalantar M, Sheikhha M, Hokmollahi F, Azimzadeh M, et al. Bunium persicum (Black Caraway) of Yazd province: Chemical assessment and Evaluation of its Antioxidant Effects. SSU J 2010; 18: 284-291.

  • 12.

    Xu G, Kuang G, Jiang W, Jiang R, Jiang D. Polydatin promotes apoptosis through upregulation the ratio of Bax/Bcl-2 and inhibits proliferation by attenuating the -catenin signaling in human osteosarcoma cells. Am J Transl Res 2016; 8: 922-931.

  • 13.

    Pappas K, Xu J, Zairis S, Zairis S, Resnick-Silverman L, Abate F, et al. P53 maintains baseline expression of multiple tumor suppressor genes. Mol Cancer Res 2017; 15: 1051-1062.

  • 14.

    Kamada R, Toguchi Y, Nomura T, Imagawa T, Sakaguchi K. Tetramer formation of tumor suppressor protein p53: Structure, Structure, function, and applications. Biopolymers 2016; 106: 598-612.

  • 15.

    Leroy B, Ballinger ML, Baran-Marszak F, Bond GL, Braithwaite A, Concin N, et al. Recommended guidelines for validation, quality control, and reporting of TP53 variants in clinical practice. Cancer Res 2017; 77: 1250-1260.

  • 16.

    Dehghan R, Hosseinpour Feizi MA, Pouladi N, Babaei E, Montazeri V, Fakhrjoo A. Association of p53 (-16ins-pro) haplotype with the decreased risk of differentiated thyroid carcinoma in Iranian-Azeri patients. Pathol Oncol Res 2015; 21: 449-454.

  • 17.

    Jiang XH, Wong BC, Lin MC, Zhu GH, KungHF, Jiang SH, et al. Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-kappaB activation in gastric cancer cells. Oncogene 2001; 20: 8009-8018.

  • 18.

    Karimi N, behbahani M, Dini G, Razmjou A. Green synthesis of ZnO nanoparticles using extract of edible and medicinal plant (Allium jesdianum). Razi J Med Sci 2018; 25: 1-7. (Persian).

  • 19.

    Rajeshkumar S, Kumar SV, Ramaiah A, Agarwal H, Lakshmi T, Roopan SM. Biosynthesis of zinc oxide nanoparticles using Mangifera indica leaves and evaluation of their antioxidant and cytotoxic properties in lung cancer (A549) cells. Enzyme Microb Technol 2018; 117: 91-95.

  • 20.

    Jahan peymay sabet B, Mahdavi-Ourtakand M, Baghbani-Arani F. Green synthesis of zinc oxide nanoparticles by Zataria multiflora extract and evaluation of its antimicrobial, cytotoxic and apoptotic effects on HT-29 cell line. Koomesh 1401; 24: 388-396. (Persian).

  • 21.

    Wahab R, Kaushik NK, Kaushik N, Choi EH, Umar A, Dwivedi S, et al. ZnO nanoparticles induces cell death in malignant human T98G gliomas, KB and non-malignant HEK cells. J Biomed Nanotech 2013; 9: 1181-1189.

  • 22.

    Selvakumari D, Deepa R, Mahalakshmi V, Subhashini P, Lakshminarayan N. Anti cancer activity of zno nanoparticles on MCF7 (breast cancer cell) and A549 (lung cancer cell). ARPN J Eng Appl Sci 2015; 10: 5418-5421.

  • 23.

    Malaikozhundan B, Vaseeharan B, Vijayakumar S, Pandiselvi K, Kalanjiam MA, Murugan K, et al. Biological therapeutics of Pongamia pinnata coated zinc oxide nanoparticles against clinically important pathogenic bacteria, fungi and MCF-7 breast cancer cells. Microb Pathog 2017; 104: 268-277.

  • 24.

    Shandiz SA, Sharifian F, Behboodi S, Ghodratpour F, Baghbani Arani F. Evaluation of metastasis suppressor genes expression and in vitro anti-cancer effects of zinc oxide nanoparticles in human breast cancer cell lines MCF-7 and T47D. Avicenna J Med Biotechnol 2021; 13: 9-14.

  • 25.

    Mozdoori N, Safarian S, Sheibani N. Augmentation of the cytotoxic effects of zinc oxide nanoparticles by MTCP conjugation: Non-canonical apoptosis and autophagy induction in human adenocarcinoma breast cancer cell lines. Mater Sci Eng C 2017; 78: 949-959.

  • 26.

    Sharifian A, Baghbani-Arani F, Sahebjami H. Effect of topotycan and zinc oxide nanoparticles combination on cytotoxicity and P53 gene expression against breast cancer (MCF-7) cell line. Koomesh 1398; 22: 192-197. (Persian).##https://doi.org/10.29252/koomesh.22.1.192.