Abstract
Nanobiotechnology has been emerging as an interesting scientific branch holds its applicability in biology, medicine etc. Exploiting the capacity of biogenic metal nanoparticles in areas like biomedicine and therapeutics with peculiarities such as eco-friendly, cheap and biocompatible, the green synthesized bimetallic nanopaticles, silver-zinc oxide nanopaticles (Ag–ZnO NPs), were chosen to find out their anticancer properties. Herein, the Ag–ZnO NPs were fabricated by using the leaf extract of Capparis zeylanica (C. zeylanica) plant. Further, the Ag–ZnO NPs were subjected to characterization, and they were tested for their anticancer potential on the breast cancer cells, MDA-MB-231.The cell viability study implied that the IC50 value of MDA-MB-231 cells was 43.46 ± 2.56, achieved at a 10 μg/ml concentration of Ag–ZnO NPs. The NPs-treated cancer cells exhibited the ROS-mediated apoptotic changes that were visualized through fluorescent microscopic images using acridine orange/ethydium bromide (AO/EB) staining, 4′,6-diamidino-2-phenylindole (DAPI), and propidium iodide (PI) staining. The findings of the current study point out that the green Ag–ZnO NPs seem to be an efficient anticancer agent.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Data available on request from the authors.
References
Aalami AH, Mesgari M, Sahebkar A (2020) Synthesis and characterization of green zinc oxide nanoparticles with antiproliferative effects through apoptosis induction and microRNA modulation in breast cancer cells. Bioinorg Chem Appl. https://doi.org/10.1155/2020/8817110
Ahamed M, Akhtar MJ, Khan MM, Alhadlaq HA (2022) Enhanced anticancer performance of eco-friendly-prepared Mo–ZnO/RGO nanocomposites: role of oxidative stress and apoptosis. ACS Omega 7(8):7103–7115. https://doi.org/10.1021/acsomega.1c06789
Alharthy SA, Tabrez S, Mirza AA, Zughaibi TA, Firoz CK, Dutta M (2022) Sugiol suppresses the proliferation of human U87 glioma cells via induction of apoptosis and cell cycle arrest. Evid Compl Alt Med. https://doi.org/10.1155/2022/7658899
Al-Mamun MA, Akter Z, Uddin MJ, Ferdaus KMKB, Hoque KMF, Ferdousi Z, Reza MA (2016) Characterization and evaluation of antibacterial and antiproliferative activities of crude protein extracts isolated from the seed of Ricinus communis in Bangladesh. BMC Compl Alter Med 16(1):1–10. https://doi.org/10.1186/s12906-016-1185-y
Alzahrani EA, Nabi A, Kamli MR, Albukhari SM, Althabaiti SA, Al-Harbi SA, Khan I, Malik MA (2023) Facile green synthesis of ZnO NPs and plasmonic Ag-Supported ZnO nanocomposite for photocatalytic degradation of methylene blue. Water 15(3):384. https://doi.org/10.3390/w15030384
Anjum NA, Adam V, Kizek R, Duarte AC, Pereira E, Iqbal M, Lukatkin AS, Ahmad I (2015) Nanoscale copper in the soil—plant system—toxicity and underlying potential mechanisms. Env Res 138:306–325. https://doi.org/10.1016/j.envres.2015.02.019
AshaRani PV, Low Kah Mun G, Hande MP, Valiyaveettil S (2009) Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3(2):279–290. https://doi.org/10.1021/nn800596w
Azizi M, Ghourchian H, Yazdian F, Bagherifam S, Bekhradnia S, Nyström B (2017) Anti-cancerous effect of albumin coated silver nanoparticles oMDA-MB 231 human breast cancer cell line. Sci Rep 7(1):1–18. https://doi.org/10.1038/s41598-017-05461-3
Aziz N, Faraz M, Sherwani MA, Fatma T, Prasad R (2019) Illuminating the anticancerous efficacy of a new fungal chassis for silver nanoparticle synthesis. Frontiers in Chem 7:65. https://doi.org/10.3389/fchem.2019.00065
Banerjee PP, Bandyopadhyay A, Harsha SN, Policegoudra RS, Bhattacharya S, Karak N, Chattopadhyay A (2017) Mentha arvensis (Linn.)-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells. Breast Cancer Targets Ther 9:265. https://doi.org/10.2147/BCTT.S130952
Baskic D, Popovic S, Ristic P, Arsenijevic NN (2006) Analysis of cycloheximide-induced apoptosis in human leukocytes: Fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biol Int 30(11):924–932. https://doi.org/10.1016/j.cellbi.2006.06.016
Bisht G, Rayamajhi S (2016) ZnO nanoparticles: a promising anticancer agent. Nanobiomedicine 3:9. https://doi.org/10.5772/63437
Boskabadi SH, Balanezhad SZ, Neamati A, Tabrizi MH (2020) The green-synthesized zinc oxide nanoparticle as a novel natural apoptosis inducer in human breast (MCF7 and MDA-MB231) and colon (HT-29) cancer cells. Inorg Nano-Metal Chem 51(5):733–743. https://doi.org/10.1080/24701556.2020.1808991
Carmody RJ, Cotter TG (2001) Signalling apoptosis: a radical approach. Redox Rep 6(2):77–90. https://doi.org/10.1179/135100001101536085
Cherukula K, Manickavasagam Lekshmi K, Uthaman S, Cho K, Cho CS, Park IK (2016) Multifunctional inorganic nanoparticles: recent progress in thermal therapy and imaging. Nanomaterial 6(4):76. https://doi.org/10.3390/nano6040076
Clark JH, Macquarrie DJ (eds) (2008) Handbook of green chemistry and technology. John Wiley & Sons, New Jersey
Czabotar PE, Lessene G, Strasser A, Adams JM (2014) Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 15(1):49–63. https://doi.org/10.1038/nrm3722
Daniel MC, Astruc D (2004) Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 104(1):293–346. https://doi.org/10.1021/cr030698+
Dos Santos CA, Seckler MM, Ingle AP, Gupta I, Galdiero S, Galdiero M, Gade A, Rai M (2014) Silver nanoparticles: therapeutical uses, toxicity, and safety issues. J Pharm Sci 103(7):1931–1944. https://doi.org/10.1002/jps.24001
Elderdery AY, Alhamidi AH, Elkhalifa AM, Althobiti MM, Tebien EM, Omer NE, Hamza SM, Alanazi F, Alzahrani B, Subbiah SK, Mok PL (2022) Synthesis and characterization of ZnO–TiO2–chitosan–escin metallic nanocomposites: evaluation of their antimicrobial and anticancer activities. Green Process Syn 11(1):1026–1039. https://doi.org/10.1515/gps-2022-0086
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516. https://doi.org/10.1080/01926230701320337
Fuchs Y, Steller H (2011) Programmed cell death in animal development and disease. Cell 147(4):742–758. https://doi.org/10.1016/j.cell.2011.10.033
Gao J, Ren X, Chen D, Tang F, Ren J (2007) Bimetallic Ag–Pt hollow nanoparticles: synthesis and tunable surface plasmon resonance. Scripta Mat 57(8):687–690. https://doi.org/10.1016/j.scriptamat.2007.06.049
George BPA, Kumar N, Abrahamse H, Ray SS (2018) Apoptotic efficacy of multifaceted biosynthesized silver nanoparticles on human adenocarcinoma cells. Sci Rep 8(1):1–14. https://doi.org/10.1038/s41598-018-32480-5
Gupta SC, Hevia D, Patchva S, Park B, Koh W, Aggarwal BB (2012) Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxid Redox Signal 16(11):1295–1322. https://doi.org/10.1089/ars.2011.4414
Gurunathan S, Park JH, Han JW, Kim JH (2015) Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy. Int J Nanomed 10:4203. https://doi.org/10.2147/IJN.S83953
Gurunathan S, Han JW, Eppakayala V, Jeyaraj M, Kim JH (2013) Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells. BioMed Res Internat. https://doi.org/10.1155/2013/535796
Hameed S, Khalil AT, Ali M, Numan M, Khamlich S, Shinwari ZK, Maaza M (2019) Greener synthesis of ZnO and Ag–ZnO nanoparticles using Silybum marianum for diverse biomedical applications. Nanomed 14(6):655–673. https://doi.org/10.2217/nnm-2018-0279
Hano C, Abbasi BH (2021) Plant-based green synthesis of nanoparticles: production, characterization and applications. Biomole 12(1):31. https://doi.org/10.3390/biom12010031
Haque S, Norbert CC, Acharyya R, Mukherjee S, Kathirvel M, Patra CR (2021) Biosynthesized silver nanoparticles for cancer therapy and in vivo bioimaging. Canc 13(23):6114. https://doi.org/10.3390/cancers13236114
Hashem AH, El-Sayyad GS (2023) Antimicrobial and anticancer activities of biosynthesized bimetallic silver–zinc oxide nanoparticles (Ag–ZnO NPs) using pomegranate peel extract. Biomass Conv Bioref. https://doi.org/10.1007/s13399-023-04126-8
Irfan M, Munir H, Ismail H (2021) Moringa oleifera gum based silver and zinc oxide nanoparticles: green synthesis, characterization and their antibacterial potential against MRSA. Biomat Res 25(1):17. https://doi.org/10.1186/s40824-021-00219-5
Jain N, Jain P, Rajput D, Patil UK (2021) Green synthesized plant-based silver nanoparticles: therapeutic prospective for anticancer and antiviral activity. Micro and Nano Sys Lett 9(1):1–24. https://doi.org/10.1186/s40486-021-00131-6
Jemal A, Thomas A, Murray T, Thun M (2002) Cancer statistics, 2002. Ca-A Canc J Clin 52(1):23–47. https://doi.org/10.3322/canjclin.52.1.23
Jobe MC, Mthiyane DM, Mwanza M, Onwudiwe DC (2022) Biosynthesis of zinc oxide and silver/zinc oxide nanoparticles from Urginea epigea for antibacterial and antioxidant applications. Heliyon 8(12):e12243. https://doi.org/10.1016/j.heliyon.2022.e12243
Kaur P, Thakur R, Chaudhury A (2016) Biogenesis of copper nanoparticles using peel extract of Punica granatum and their antimicrobial activity against opportunistic pathogens. Green Chem Lett Rev 9(1):33–38. https://doi.org/10.1080/17518253.2016.1141238
Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Sci 275(5303):1132–1136. https://doi.org/10.1126/science.275.5303.1132
Leite M, Quinta-Costa M, Leite PS, Guimarães JE (1999) Critical evaluation of techniques to detect and measure cell death—study in a model of UV radiation of the leukaemic cell line HL60. Anal Cell Pathol 19(3–4):139–151
Li X, Xu H, Chen ZS, Chen G (2011) Biosynthesis of nanoparticles by microorganisms and their applications. J Nanomat. https://doi.org/10.1155/2011/270974
Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cellular Physiol 192(1):1–15. https://doi.org/10.1002/jcp.10119
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63. https://doi.org/10.1016/0022-1759(83)90303-4
Narayanan KB, Sakthivel N (2011) Green synthesis of biogenic metal nanoparticles by terrestrial and aquatic phototrophic and heterotrophic eukaryotes and biocompatible agents. Adv Coll Interf Sci 169(2):59–79. https://doi.org/10.1016/j.cis.2011.08.004
Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nano level. Sci 311(5761):622–627. https://doi.org/10.1126/science.1114397
Nilavukkarasi M, Vijayakumar S, Prathipkumar S (2020) Capparis zeylanica mediated bio-synthesized ZnO nanoparticles as antimicrobial, photocatalytic and anti-cancer applications. Mat Sci Ener Technol 3:335–343. https://doi.org/10.1016/j.mset.2019.12.004
Pal K, Sajjadifar S, Abd Elkodous M, Alli YA, Gomes F, Jeevanandam J, Thomas S, Sigov A (2019) Soft, self-assembly liquid crystalline nanocomposite for superior switching. Electron Mat Lett 15(1):84–101. https://doi.org/10.1007/s13391-018-0098-y
Prabst K, Engelhardt H, Ringgeler S, Hübner H (2017) Basic Colorimetric Proliferation Assays: MTT, WST, and Resazurin. In: Gilbert D, Friedrich O (eds) Cell Viability Assays. Methods in Molecular Biology, vol 1601. Humana Press: New York. https://doi.org/10.1007/978-1-4939-6960-9_1
Prasad S, Gupta SC, Tyagi AK (2017) Reactive oxygen species (ROS) and cancer: role of antioxidative nutraceuticals. Can Lett 387:95–105. https://doi.org/10.1016/j.canlet.2016.03.042
Raza MH, Siraj S, Arshad A, Waheed U, Aldakheel F, Alduraywish S, Arshad M (2017) ROS-modulated therapeutic approaches in cancer treatment. J Can Res Clin Oncol 143(9):1789–1809. https://doi.org/10.1007/s00432-017-2464-9
Riss TL, Moravec, RA, Niles AL, Duellman S, Benink HA, Worzella TJ, Minor L (2016) Cell viability assays. Assay Guidance Manual [Internet]
Selim YA, Azb MA, Ragab I, Abd El-Azim HM, M. (2020) Green synthesis of zinc oxide nanoparticles using aqueous extract of Deverra tortuosa and their cytotoxic activities. Sci Rep 10(1):3445. https://doi.org/10.1038/s41598-020-60541-1
Selvan DSA, Murugesan S, Shobana S, Lakshmi B, Veena V, Rahiman AK (2021) In vitro cytotoxicity efficacy of phytosynthesized ag/ZnO nanocomposites using Murraya koenigii and Zingiber officinale extracts. Mat Chem Phy 272:124903. https://doi.org/10.1016/j.matchemphys.2021.124903
Senapati S, Mahanta AK, Kumar S, Maiti P (2018) Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct Target Ther 3(1):7. https://doi.org/10.1038/s41392-017-0004-3
Shihabul Islam M, Sifat Rahi M, Jahangir CA, Hasan MM, Sajib SA, Haque A, Kabir SR, Faisal Hoque KM, Moni MA, Reza MA (2018) Deciphering the molecular pathways of apoptosis using leaf extract of Basella alba against ehrlichs ascites carcinoma (EAC) cell line in Swiss albino mice model. Biorxiv. https://doi.org/10.1101/485078
Shreema K, Mathammal R, Kalaiselvi V, Vijayakumar S, Selvakumar K, Senthil K (2021) Green synthesis of silver doped zinc oxide nanoparticles using fresh leaf extract Morinda citrifolia and its antioxidant potential. Mat Today: Proceed 47:2126–2131. https://doi.org/10.1016/j.matpr.2021.04.627
Silva A, Girio A, Cebola I, Santos CI, Antunes F, Barata JT (2011) Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell acute lymphoblastic leukemia cells. Leukemia 25(6):960–967
Singh J, Dutta T, Kim KH, Rawat M, Samddar P, Kumar P (2018) ‘Green’synthesis of metals and their oxide nanoparticles: applications for environmental remediation. J Nanobiotech 16(1):1–24. https://doi.org/10.1186/s12951-018-0408-4
Srinoi P, Chen YT, Vittur V, Marquez MD, Lee TR (2018) Bimetallic nanoparticles: enhanced magnetic and optical properties for emerging biological applications. Appl Sci 8(7):1106. https://doi.org/10.3390/app8071106
Subarkhan MM, Prabhu RN, Kumar RR, Ramesh R (2016) Antiproliferative activity of cationic and neutral thiosemicarbazone copper(II) complexes. RSC Adv 6(30):25082–25093. https://doi.org/10.1039/C5RA26071J
Sun B, Hu N, Han L, Pi Y, Gao Y, Chen K (2019) Anticancer activity of green synthesised gold nanoparticles from Marsdenia tenacissima inhibits A549 cell proliferation through the apoptotic pathway. Artif Cells Nanomed Biotech 47(1):4012–4019. https://doi.org/10.1080/21691401.2019.1575844
Suresh P, Doss A, Praveen Pole RP, Devika M (2023) Green synthesis, characterization and antioxidant activity of bimetallic (Ag–ZnO) nanoparticles using Capparis zeylanica leaf extract. Biomass Conv Bioref. https://doi.org/10.1007/s13399-023-03743-7
Umar H, Kavaz D, Rizaner N (2019) 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 14:87–100. https://doi.org/10.2147/IJN.S186888
Walimbe KG, Dhawal PP, Kakodkar SA (2022) Anticancer Potential of biosynthesized silver nanoparticles: a review. Europ J Biol Biotech 3(2):10–20. https://doi.org/10.24018/ejbio.2022.3.2.338
Wang X, Wang Y, Chen ZG, Shin DM (2009) Advances of cancer therapy by nanotechnology. Cancer Res Treat 41(1):1–11. https://doi.org/10.4143/crt.2009.41.1.1
Wang SW, Lee CH, Lin MS, Chi CW, Chen YJ, Wang GS, Liao KW, Chiu LP, Wu SH, Huang DM, Chen L (2020) ZnO nanoparticles induced caspase-dependent apoptosis in gingival squamous cell carcinoma through mitochondrial dysfunction and p70S6K signaling pathway. Int J Mol Sci 21(5):1612
Watson AS, Mortensen M, Simon AK (2011) Autophagy in the pathogenesis of myelodysplastic syndrome and acute myeloid leukemia. Cell Cycle 10(11):1719–1725. https://doi.org/10.4161/cc.10.11.15673
Wiesmann N, Tremel W, Brieger J (2020) Zinc oxide nanoparticles for therapeutic purposes in cancer medicine. J Mat Chem B 8(23):4973–4989. https://doi.org/10.1039/D0TB00739K
Xu J, Huang Y, Zhu S, Abbes N, Jing X, Zhang L (2021) A review of the green synthesis of ZnO nanoparticles using plant extracts and their prospects for application in antibacterial textiles. J Eng Fib Fabrics. https://doi.org/10.1177/15589250211046242
Yhee JY, Son S, Kim N, Choi K, Kwon IC (2014) Theranostic applications of organic nanoparticles for cancer treatment. Bull 39(3):239–249. https://doi.org/10.1557/mrs.2014.30
Yin JJ, Liu J, Ehrenshaft M, Roberts JE, Fu PP, Mason RP, Zhao B (2012) Phototoxicity of nano titanium dioxides in HaCaT keratinocytes—generation of reactive oxygen species and cell damage. Toxicol Appl Pharmacol 263(1):81–88. https://doi.org/10.1016/j.taap.2012.06.001
Author information
Authors and Affiliations
Contributions
AD, TPKPR & PS: Experimental designing, Result Analysis & Writing. SS, GR &, RPP: Editing & Proof reading.
Corresponding author
Ethics declarations
Ethical statement
Not applicable.
Conflict of interest
No conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Suresh, P., Doss, A., Rajeswari, G. et al. Capparis zeylanica-mediated Ag/ZnO nanoparticles and their antiproliferative efficacy via nuclear apoptosis. ADV TRADIT MED (ADTM) (2024). https://doi.org/10.1007/s13596-024-00752-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s13596-024-00752-3