The Effect of Biosynthesized Zinc Oxide Nanoparticles Capped by Scenedesmus obliquus on Apoptosis and Gene Expression of p53 and VEGF in Breast Cancer Cell Line

Document Type : Research Paper

Authors

Department of Plant Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

Abstract

Breast cancer is the most prevalent form of cancer in women. This condition poses a significant public health concern that requires further research to understand its prognosis better and proper treatment options. Scenedesmus obiquus algae has unique biological compounds that can be effective in the synthesis of nanoparticles. The objective of this study is to examine how the impact of ZnO NPs, which are produced by the S. obliquus algae, affects cell death and gene expression in a breast cancer cell line. MDA-MB-231 cells are a subtype of breast cancer cells known for their high aggressiveness and connection to the triple-negative breast cancer subtype. The impact of biosynthesized ZnO NPs (0, 800, 1600, and 2400 μg/ml) on apoptosis of the MDA-MB-231 cell line and VEGF and p53 gene expression in breast cancer cells was assessed. The absorption band at 362 nm exhibited an absorption maximum that confirmed the synthesis of ZnO NPs. Zinc oxide nanoparticles exhibited significant toxicity towards MDA-MB-231 cell lines, with an IC50 value of 1050 μg/ml. The findings indicated that 1600 μg/ml of ZnO NPs had the most potent inhibitory effect on the growth (71.1%) of MDA-MB-231cultures. The ZnO NPs increased the expression of p53 and reduced the expression of VEGF. This study demonstrates that nanoparticles created using S. obliquus algae, which possess anti-cancer properties, have potential effectiveness in treating cancer. However, it is essential to conduct appropriate in vivo studies to investigate its impact on additional biochemical indicators.

Keywords

Main Subjects


  1. Saunders F.R., Wallace H.M. On the natural chemoprevention of cancer. Plant Physiol Biochem. 2010;48(7):621-26.
  2. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2018. CA: Cancer J Clin. 2018;68(1):7-30.
  3. Farokhzad O.C., Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16-20.
  4. McGuire A., Brown J.A., Malone C., McLaughlin R., Kerin M.J. Effects of age on the detection and management of breast cancer. Cancers. 2015;7(2):908-29.
  5. Badkoobeh P., Parivar K., Kalantar S.M., Hosseini S.D., Salabat A. Effect of nano-zinc oxide on doxorubicin-induced oxidative stress and sperm disorders in adult male Wistar rats. Iran J Reprod Med. 2013;11(5):355.
  6. Abboud Y., Saffaj T., Chagraoui A., El Bouari A., Brouzi K., Tanane O., Ihssane B. Biosynthesis, characterization and antimicrobial activity of copper oxide nanoparticles (CONPs) produced using brown alga extract (Bifurcaria bifurcata). Appl Nanosci. 2014;4:571-76.
  7. Chang Y.-N., Zhang M., Xia L., Zhang J., Xing G. The toxic effects and mechanisms of CuO and ZnO nanoparticles. Materials. 2012;5(12):2850-71.
  8. Blinova I., Ivask A., Heinlaan M., Mortimer M., Kahru A. Ecotoxicity of nanoparticles of CuO and ZnO in natural water. Environ Pollut. 2010;158(1):41-47.
  9. Yoo C., Jun S.-Y., Lee J.-Y., Ahn C.-Y., Oh H.-M. Selection of microalgae for lipid production under high levels carbon dioxide. Bioresour Technol. 2010;101(1):S71-S74.
  10. Göksan T., Ak İ., Kılıç C. Growth characteristics of the alga Haematococcus pluvialis flotow as affected by nitrogen source, vitamin, light and aeration. Turk J Fish Aquat Sci. 2011;11(3):377-83.
  11. Sahayaraj K., Rajesh S. Bionanoparticles: synthesis and antimicrobial applications. Science against microbial pathogens: communicating current research and technological advances. 2011;23:228-44.
  12. Merin D.D., Prakash S., Bhimba B.V. Antibacterial screening of silver nanoparticles synthesized by marine micro algae. Asian Pac J trop Med. 2010;3(10):797-99.
  13. Chugh D., Viswamalya V., Das B. Green synthesis of silver nanoparticles with algae and the importance of capping agents in the process. J Genet Eng Biotechnol. 2021;19(1):126.
  14. Zachleder V., Wittenburg E., Abarzua S. Factors controlling the inhibitory effects of 3, 4-benzo (a) pyrene on the chlorococcal alga Scenedesmus quadricauda. Arch Hydrobiol Suppl. 1986;73:281-96.
  15. Abedin R.M., Taha H.M. Antibacterial and antifungal activity of cyanobacteria and green microalgae. Evaluation of medium components by Plackett-Burman design for antimicrobial activity of Spirulina platensis. Glob J Biochem Biotech. 2008;3(1):22-31.
  16. Najdenski H.M., Gigova L.G., Iliev I.I., Pilarski P.S., Lukavský J., Tsvetkova I.V., Ninova M.S., Kussovski V.K. Antibacterial and antifungal activities of selected microalgae and cyanobacteria. Int J Food Sci tech. 2013;48(7):1533-40.
  17. Abd El Baky H., El-Baroty G., Ibrahem E. Antiproliferation and antioxidant properties of lipid extracts of the microalgae Scenedesmus obliquus grown under stress conditions. Der Pharma Chemica. 2014;6(5):24-34.
  18. Silambarasan T., Kumaran M., Kalaichelvan D., Dhandapani R. Antioxidant and antiproliferative activity of the extract from fresh water algae Scenedesmus obliquus RDS01. Int J Adv Sci Eng. 2014;1:37-40.
  19. Khanna P., Kaur A., Goyal D. Algae-based metallic nanoparticles: Synthesis, characterization and applications. J microbiol methods. 2019;163:105656.
  20. Bellinger E.G., Sigee D.C. A key to the more frequently occurring freshwater algae. Freshwater algae. 2010:137-244.
  21. Gharanjik B., Ghadikalaei K. Atlas of Seaweeds on the Persian Gulf and Oman Seas. 2012; 202,
  22. Barbarino E., Lourenço S.O. An evaluation of methods for extraction and quantification of protein from marine macro-and microalgae. J Appl Phycol. 2005;17:447-60.
  23. Dash S.K., Ghosh T., Roy S., Chattopadhyay S., Das D. Zinc sulfide nanoparticles selectively induce cytotoxic and genotoxic effects on leukemic cells: involvement of reactive oxygen species and tumor necrosis factor alpha. J Appl Toxicol. 2014;34(11):1130-44.
  24. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-08.
  25. Rajakannu S., Shankar S., Perumal S., Subramanian S., Dhakshinamoorthy G.P. Biosynthesis of silver nanoparticles using Garcinia mangostana fruit extract and their antibacterial, antioxidant activity. Int J Curr Microbiol Appl Sci. 2015;4(1):944-52.
  26. Ullah Khan S., Saleh T.A., Wahab A., Khan M.H.U., Khan D., Ullah Khan W., Rahim A., Kamal S., Ullah Khan F., Fahad S. Nanosilver: new ageless and versatile biomedical therapeutic scaffold. Int j Nanomed. 2018:733-62.
  27. Thirumurugan A., Aswitha P., Kiruthika C., Nagarajan S., Christy A.N. Green synthesis of platinum nanoparticles using Azadirachta indica–An eco-friendly approach. Mater Lett. 2016;170:175-78.
  28. Madhavan M., Elsa R.P., Francis A., Benny G.M., Wilson A. Green synthesis of silver nanoparticles from fruit rind extract of Garcinia mangostana L. and evaluation of antibacterial properties. Plant Arch. 2021;21(2):279-83.
  29. Rasmussen J.W., Martinez E., Louka P., Wingett D.G. Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert Opin Drug Deliv. 2010;7(9):1063-77.
  30. Rautela A., Rani J. Green synthesis of silver nanoparticles from Tectona grandis seeds extract: characterization and mechanism of antimicrobial action on different microorganisms. J Agri Sci Tech. 2019;10(1):1-10.
  31. Gaffar N.A., Zahid M., Asghar A., Shafiq M.F., Jelani S., Rehan F. Biosynthesized metallic nanoparticles: A new era in cancer therapy. Archiv der Pharmazie. 2024;357(7):e2300712.
  32. Beigi S., Salehzadeh A., Habibbollahi H., Sadat Shandiz S.A., Safa F. The effect of ZnO nanoparticles functionalized with Glutamic Acid and conjugated with Thiosemicarbazide on the expression of Bax, caspase-3, and bcl-2 genes in Adenocarcinoma Gastric (AGS) Cell Line. J Anim Biol. 2022;14(4):37-50.
  33. Padmanabhan A., Kaushik M., Niranjan R., Richards J.S., Ebright B., Venkatasubbu G.D. Zinc oxide nanoparticles induce oxidative and proteotoxic stress in ovarian cancer cells and trigger apoptosis independent of p53-mutation status. Appl Surf Sci. 2019;487:807-18.
  34. Moratin H., Scherzad A., Gehrke T., Ickrath P., Radeloff K., Kleinsasser N., Hackenberg S. Toxicological characterization of ZnO nanoparticles in malignant and non‐malignant cells. Environ Mol Mutagen. 2018;59(3):247-59.
  35. Yuan L., Wang Y., Wang J., Xiao H., Liu X. Additive effect of zinc oxide nanoparticles and isoorientin on apoptosis in human hepatoma cell line. Toxicol lett. 2014;225(2):294-304.
  36. Aswathi Sreenivasan C., Justi Jovitta C., Suja S. Synthesis of ZnO nanoparticles from Alpinia purpurata and their antimicrobial properties. Res J Pharm Bio Chem Sci. 2012;3:1206-13.
  37. Sharif A.P., Habibi K., Bijarpas Z.k., Tolami H.F., Alkinani T.A., Jameh M., Dehkaei A.A., Monhaser S.K., Daemi H.B., Mahmoudi A. Cytotoxic Effect of a Novel GaFe2O4@ Ag nanocomposite synthesized by Scenedesmus obliquus on gastric cancer cell line and evaluation of BAX, Bcl-2 and CASP8 genes expression. J. Clust Sci. 2023;34(2):1065-75.
  38. George B.P., Rajendran N.K., Houreld N.N., Abrahamse H. Rubus capped zinc oxide nanoparticles induce apoptosis in MCF-7 breast cancer cells. Molecules. 2022;27(20):6862.
  39. Subramaniyan S., Kamaraj Y., Kumaresan V., Kannaiyan M., David E., Ranganathan B., Selvaraj V., Balupillai A. Green synthesized zinc oxide nanoparticles induce apoptosis by suppressing PI3K/Akt/mTOR signaling pathway in osteosarcoma MG63 cells. GTM. 2022;1(1):1-12.
  40. Collis S.J., DeWeese T.L., Jeggo P.A., Parker A.R. The life and death of DNA-PK. Oncogene. 2005;24(6):949-61.
  41. Inoue T., Wu L., Stuart J., Maki C.G. Control of p53 nuclear accumulation in stressed cells. FEBS lett. 2005;579(22):4978-84.
  42. Grawish M.E. Effects of Spirulina platensis extract on Syrian hamster cheek pouch mucosa painted with 7, 12-dimethylbenz [a] anthracene. Oral Oncol. 2008;44(10):956-62.
  43. Baghbani A.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. 2020; 22(1): 192-97.
  44. Shamsi H., Yari R., Salehzadeh A. Assessment the effect of BiFe2O4@ Ag nanocomposite biosynthesized by Scenedesmus obliquus on expression of CAD, CASP8 and p53 genes in gastric cancer cell line. J Appl Plant Biol. 2023;11(2):115-34.
  45. Torres-Díaz M., Abreu-Takemura C., Díaz-Vázquez L.M. Microalgae peptide-stabilized gold nanoparticles as a versatile material for biomedical applications. Life. 2022;12(6):831.
  46. Rudi L., Zinicovscaia I., Cepoi L., Chiriac T., Peshkova A., Cepoi A., Grozdov D. Accumulation and effect of silver nanoparticles functionalized with spirulina platensis on rats. Nanomaterials. 2021;11(11):2992.
  47. Fazeli M., Zarei N., Moazen B., Nejatollahi F. Anti-proliferative effects of human anti-FZD7 single chain antibodies on colorectal cancer cells. Shiraz Med J. 2017;18(3):e59936.