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Anticancer Effects of Gold Nanoparticles by Inducing Apoptosis in Bladder Cancer 5637 Cells

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Abstract

Nanotechnology is a developing and revolutionary science that has been widely recommended for diagnosis and treatment of cancer. Among the various nanoparticles used in nanotechnology, gold nanoparticles (AuNPs) have attracted much attentions due to their promising anticancer properties. Despite the potential advantages of AuNPs, their apoptotic and anti-angiogenic effects have not yet been reported on human bladder cancer 5637 cells. This motivated us to evaluate (reactive oxygen species) ROS-mediated apoptosis in 5637 cells. For this task, inhibitory effect of AuNPs was investigated after 24-h exposure to different concentrations of AuNPs by MTT assay. Also, apoptosis level was assessed by ROS production, flow cytometry, and Hoechst 33,258 staining. Besides, mRNA expression of B-cell lymphoma protein 2 (Bcl-2), Bcl-2-associated X (Bax), vascular endothelial growth factor A (VEGFA) genes, and caspase-3,7 activity were determined by qRT-PCR and colorimetric assay, respectively. Moreover, migration rate was evaluated by wound healing assay. MTT results demonstrate that AuNPs can reduce 5637-cell viability in a dose-dependent manner, while fluorimetric assay data show significant increased ROS production in 25 and 50 µg/ml-treated cells. It is also observed that AuNPs lead to Bax overexpression and downregulation of Bcl-2 and VEGFA genes. In line with this, flow cytometry results show increased levels of apoptosis in 25 and 50 µg/ml AuNP-treated cells (p < 0.05). Similarly, Hoechst staining indicates a remarkable increase in cells with apoptotic morphology after treating with AuNPs. Overall, our findings show that AuNPs significantly provoke ROS production, induce apoptosis, and suppress cell migration in bladder cancer 5637 cells.

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References

  1. Kanchana A, Balakrishna M (2011) Anti-cancer effect of saponins isolated from Solanum trilobatum leaf extract and induction of apoptosis in human larynx cancer cell lines. Int J Pharm Pharm Sci 3(4):356–364

    CAS  Google Scholar 

  2. Bae KH, Chung HJ, Park TG (2011) Nanomaterials for cancer therapy and imaging. Mol Cells 31(4):295–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Isharwal S, Konety B (2015) Non-muscle invasive bladder cancer risk stratification. Indian J Urol 31(4):289

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kamat AM et al (2016) Bladder cancer. The Lancet 388(10061):2796–2810

    Article  Google Scholar 

  5. Askeland EJ, Newton MR, O’Donnell MA, Luo Y (2012) Bladder cancer immunotherapy: BCG and beyond. Adv Urol 2012:181987

  6. Rajeshkumar S (2016) Anticancer activity of eco-friendly gold nanoparticles against lung and liver cancer cells. J Genet Eng Biotechnol 14(1):195–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5(3):161–171

  8. Salem SS, Fouda A (2021) Green synthesis of metallic nanoparticles and their prospective biotechnological applications: an overview. Biol Trace Elem Res 199(1):344–370

    Article  CAS  PubMed  Google Scholar 

  9. Hassan SE-D et al (2019) Endophytic actinomycetes Streptomyces spp mediated biosynthesis of copper oxide nanoparticles as a promising tool for biotechnological applications. J Biol Inorg Chem 24(3):377–393

    Article  CAS  PubMed  Google Scholar 

  10. Shaheen TI, Fouda A, Salem SS (2021) Integration of cotton fabrics with biosynthesized CuO nanoparticles for bactericidal activity in the terms of their cytotoxicity assessment. Ind Eng Chem Res 60(4):1553–1563

    Article  CAS  Google Scholar 

  11. Mohamed AA et al (2019) Fungal strain impacts the shape, bioactivity and multifunctional properties of green synthesized zinc oxide nanoparticles. Biocatal Agric Biotechnol 19:101103

    Article  Google Scholar 

  12. Fouda A et al (2018) In-vitro cytotoxicity, antibacterial, and UV protection properties of the biosynthesized zinc oxide nanoparticles for medical textile applications. Microb Pathog 125:252–261

    Article  CAS  PubMed  Google Scholar 

  13. Soliman AM et al (2021) Green approach to overcome the resistance pattern of Candida spp. using biosynthesized silver nanoparticles fabricated by Penicillium chrysogenum F9. Biol Trace Elem Res 199:800–811

    Article  PubMed  Google Scholar 

  14. Alsharif SM et al (2020) Multifunctional properties of spherical silver nanoparticles fabricated by different microbial taxa. Heliyon 6(5):e03943

    Article  PubMed  PubMed Central  Google Scholar 

  15. Fouda A et al (2020) Antimicrobial, antioxidant and larvicidal activities of spherical silver nanoparticles synthesized by endophytic Streptomyces spp. Biol Trace Elem Res 195(2):707–724

    Article  CAS  PubMed  Google Scholar 

  16. Fouda A et al (2021) Photocatalytic degradation of real textile and tannery effluent using biosynthesized magnesium oxide nanoparticles (MgO-NPs), heavy metal adsorption, phytotoxicity, and antimicrobial activity. J Environ Chem Eng 9(4):105346

    Article  CAS  Google Scholar 

  17. Krishnaraj C et al (2014) Acalypha indica Linn: biogenic synthesis of silver and gold nanoparticles and their cytotoxic effects against MDA-MB-231, human breast cancer cells. Biotechnology Reports 4:42–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sztandera K, Gorzkiewicz M, Klajnert-Maculewicz B (2018) Gold nanoparticles in cancer treatment. Mol Pharm 16(1):1–23

    Article  PubMed  CAS  Google Scholar 

  19. Huang K et al (2012) Size-dependent localization and penetration of ultrasmall gold nanoparticles in cancer cells, multicellular spheroids, and tumors in vivo. ACS Nano 6(5):4483–4493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bin-Jumah MN et al (2020) Molecular mechanism of cytotoxicity, genotoxicity, and anticancer potential of green gold nanoparticles on human liver normal and cancerous cells. Dose-Response 18(2):1559325820912154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pistritto G et al (2016) Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 8(4):603

    Article  CAS  Google Scholar 

  22. Mohamed H, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N (2014) Apoptosis and molecular targeting therapy in cancer. BioMed Res Int 2014:150845

  23. Siddiqui WA, Ahad A, Ahsan H (2015) The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch Toxicol 89(3):289–317

    Article  CAS  PubMed  Google Scholar 

  24. Tang X et al (2010) Nitroalkenes induce rat aortic smooth muscle cell apoptosis via activation of caspase-dependent pathways. Biochem Biophys Res Commun 397(2):239–244

    Article  CAS  PubMed  Google Scholar 

  25. Sharma V, Anderson D, Dhawan A (2012) Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis 17(8):852–870

    Article  CAS  PubMed  Google Scholar 

  26. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ajdari Z et al (2016) Novel gold nanoparticles reduced by Sargassum glaucescens: preparation, characterization and anticancer activity. Molecules 21(3):123

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Pérez-Hernández M et al (2015) Dissecting the molecular mechanism of apoptosis during photothermal therapy using gold nanoprisms. ACS Nano 9(1):52–61

    Article  PubMed  CAS  Google Scholar 

  29. Chen L, Wu L-Y, Yang W-X (2018) Nanoparticles induce apoptosis via mediating diverse cellular pathways. Nanomedicine 13(22):2939–2955

    Article  CAS  PubMed  Google Scholar 

  30. Wu T et al (2019) Synthesis and characterization of gold nanoparticles from Abies spectabilis extract and its anticancer activity on bladder cancer T24 cells. Artif Cells Nanomed Biotechnol 47(1):512–523

    Article  PubMed  CAS  Google Scholar 

  31. Baghbani-Arani F et al (2017) Photo-catalytic, anti-bacterial, and anti-cancer properties of phyto-mediated synthesis of silver nanoparticles from Artemisia tournefortiana Rchb extract. J Photochem Photobiol, B 173:640–649

    Article  CAS  Google Scholar 

  32. Behboodi S et al (2019) Green engineered biomolecule-capped silver nanoparticles fabricated from Cichorium intybus extract: in vitro assessment on apoptosis properties toward human breast cancer (MCF-7) cells. Biol Trace Elem Res 187(2):392–402

    Article  CAS  PubMed  Google Scholar 

  33. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  34. He F (2011) Bradford protein assay. Bio-protocol 20:e45

  35. Maroufi NF et al (2020) The apatinib inhibits breast cancer cell line MDA-MB-231 in vitro by inducing apoptosis, cell cycle arrest, and regulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Breast Cancer 27(4):613–620

    Article  PubMed  Google Scholar 

  36. Mukherjee S, Patra CR (2016) Therapeutic application of anti-angiogenic nanomaterials in cancers. Nanoscale 8(25):12444–12470

    Article  CAS  PubMed  Google Scholar 

  37. Singh SP et al (2021) Silver nanoparticles synthesized using carica papaya leaf extract (AgNPs-PLE) causes cell cycle arrest and apoptosis in human prostate (DU145) cancer cells. Biol Trace Elem Res 199(4):1316–1331

    Article  CAS  PubMed  Google Scholar 

  38. Jeyarani S et al (2020) Biomimetic gold nanoparticles for its cytotoxicity and biocompatibility evidenced by fluorescence-based assays in cancer (MDA-MB-231) and non-cancerous (HEK-293) cells. J Photochem Photobiol B Biol 202:111715

    Article  CAS  Google Scholar 

  39. Clarance P et al (2020) Green synthesis and characterization of gold nanoparticles using endophytic fungi Fusarium solani and its in-vitro anticancer and biomedical applications. Saudi J Biol Sci 27(2):706–712

    Article  CAS  PubMed  Google Scholar 

  40. Rajendran I et al (2021) The apoptotic effect of Ferulic acid-synthesized gold nanoparticles against human epidermoid carcinoma (A431) cells via activation of caspase-3 pathway. J Drug Delivery Sci Technol 63:102478

    Article  CAS  Google Scholar 

  41. Botteon C et al (2021) Biosynthesis and characterization of gold nanoparticles using Brazilian red propolis and evaluation of its antimicrobial and anticancer activities. Sci Rep 11(1):1–16

    Article  CAS  Google Scholar 

  42. Zhao X et al (2018) Photothermal exposure of polydopamine-coated branched Au–Ag nanoparticles induces cell cycle arrest, apoptosis, and autophagy in human bladder cancer cells. Int J Nanomed 13:6413

    Article  CAS  Google Scholar 

  43. Regina A-R, Rosário P-L, Lio F-G, Carlos P, Lúcio S, Aura C, Paula O (2013) Synergistic effect between cisplatin and sunitinib malate on human urinary bladder-cancer cell lines. BioMed Res Int 2013:791406

  44. Xu X et al (2015) Differentially expressed genes and microRNAs in bladder carcinoma cell line 5637 and T24 detected by RNA sequencing. Int J Clin Exp Pathol 8(10):12678

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Ramalingam V et al (2017) Gold nanoparticle induces mitochondria-mediated apoptosis and cell cycle arrest in nonsmall cell lung cancer cells. Gold Bulletin 50(2):177–189

    Article  CAS  Google Scholar 

  46. Qian L et al (2019) Synthesis and characterization of gold nanoparticles from aqueous leaf extract of Alternanthera sessilis and its anticancer activity on cervical cancer cells (HeLa). Artif Cells Nanomed Biotechnol 47(1):1173–1180

    Article  CAS  PubMed  Google Scholar 

  47. Datkhile KD et al (2021) Biogenic synthesis of gold nanoparticles using Argemone mexicana L. and their cytotoxic and genotoxic effects on human colon cancer cell line (HCT-15). J Genet Eng Biotechnol 19(1):1–11

    Article  Google Scholar 

  48. Steckiewicz KP et al (2019) Impact of gold nanoparticles shape on their cytotoxicity against human osteoblast and osteosarcoma in in vitro model. Evaluation of the safety of use and anti-cancer potential. J Mater Sci Mater Med 30(2):22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Chang Y et al (2021) Cytotoxicity, anti-acute leukemia, and antioxidant properties of gold nanoparticles green-synthesized using Cannabis sativa L leaf aqueous extract. Arab J Chem 14(4):103060

    Article  CAS  Google Scholar 

  50. Kumar K, Sabarwal A, Singh RP (2019) Mancozeb selectively induces mitochondrial-mediated apoptosis in human gastric carcinoma cells through ROS generation. Mitochondrion 48:1–10

    Article  CAS  PubMed  Google Scholar 

  51. Vairavel M, Devaraj E, Shanmugam R (2020) An eco-friendly synthesis of Enterococcus sp.–mediated gold nanoparticle induces cytotoxicity in human colorectal cancer cells. Environ Sci Pollut Res 27(8):8166–8175

    Article  CAS  Google Scholar 

  52. Kowsalya E, MosaChristas K, Jaquline CRI, Balashanmugam P, Devasena T (2021) Gold nanoparticles induced apoptosis via oxidative stress and mitochondrial dysfunctions in MCF‐7 breast cancer cells. Appl Organomet Chem 35(1):e6071

  53. Piktel E et al (2021) ROS-mediated apoptosis and autophagy in ovarian cancer cells treated with peanut-shaped gold nanoparticles. Int J Nanomed 16:1993

    Article  Google Scholar 

  54. Yun Z et al (2020) Biosynthesis of gold nanoparticles using Vetex negundo and evaluation of pro-apoptotic effect on human gastric cancer cell lines. J Photochem Photobiol B Biol 203:111749

    Article  CAS  Google Scholar 

  55. Singh AK et al (2019) Green synthesis of gold nanoparticles from Dunaliella salina, its characterization and in vitro anticancer activity on breast cancer cell line. J Drug Delivery Sci Technol 51:164–176

    Article  CAS  Google Scholar 

  56. Roh Y-J et al (2016) The antiangiogenic effects of gold nanoparticles on experimental choroidal neovascularization in mice. Invest Ophthalmol Vis Sci 57(15):6561–6567

    Article  CAS  PubMed  Google Scholar 

  57. Pan Y, Wu Q, Qin L, Cai J, Du B (2014) Gold nanoparticles inhibit VEGF165-induced migration and tube formation of endothelial cells via the Akt pathway. Biomed Res Int 2014:418624

  58. Liu F, Ma D, Chen W, Chen X, Qian Y, Zhao Y, Hu T, Yin R, Zhu Y, Zhang Y, Zhang Y (2019) Gold nanoparticles suppressed proliferation, migration, and invasion in papillary thyroid carcinoma cells via downregulation of CCT3. J Nanomater 6:1687340

  59. Saeed BA et al (2019) Antiangiogenic properties of nanoparticles: a systematic review. Int J Nanomed 14:5135

    Article  CAS  Google Scholar 

  60. Hajebi S et al (2019) Rapeseed flower pollen bio-green synthesized silver nanoparticles: a promising antioxidant, anticancer and antiangiogenic compound. J Biol Inorg Chem 24(3):395–404

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The present study has been extracted from a MSc thesis at Hamadan University of Medical Sciences, Iran.

Funding

The study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences, Iran (No. 990119162).

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Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Sajedeh Daei, Nasrin Ziamajidi & Roghayeh Abbasalipourkabir

  2. Medical Biotechnology Research Center, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran

    Korosh Khanaki

  3. Department of Molecular Medicine and Genetics, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Fatemeh Bahreini

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  1. Sajedeh Daei
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  2. Nasrin Ziamajidi
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  3. Roghayeh Abbasalipourkabir
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  4. Korosh Khanaki
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  5. Fatemeh Bahreini
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Contributions

S.D. did all experiments and wrote the manuscript, N.Z. generated and developed the study hypothesis and design, R.A. analyzed and interpreted the data, K.K. revised the manuscript, and F.B. completed the final version of manuscript.

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Correspondence to Nasrin Ziamajidi.

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Daei, S., Ziamajidi, N., Abbasalipourkabir, R. et al. Anticancer Effects of Gold Nanoparticles by Inducing Apoptosis in Bladder Cancer 5637 Cells. Biol Trace Elem Res 200, 2673–2683 (2022). https://doi.org/10.1007/s12011-021-02895-9

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