Erdal SÖNMEZ, Ayşenur YAZICI, Hasan TÜRKEZ, Elanur AYDIN KARATAŞ, Kübra Nur BAYINDIRLI, Özlem ÖZDEMİR TOZLU, Süleyman KERLİ

Investigating the Effect of Yttrium Oxide Nanoparticle in U87MG Glioma and PC3 ProstateCancer: Molecular Approaches

Yttrium oxide ($Y_2O_3$) nanoparticles have very wide application areas such as biologicalimaging, photodynamic therapy, the material sciences, in the chemical synthesis of inorganiccompounds, additives in plastic, paint, steel, optics, and iron. Potential risks to human health and theenvironment should be evaluated in a multi-dimensional perspective when developing nanoparticles forthose applications. Therefore, in this research, we aimed to investigate changes in gene expressionprofiles (genes involved in different biological pathways) influenced by commonly Yttrium oxide($Y_2O_3$) nanoparticle in human U87MG glioma and PC3 prostate cancer cell lines in vitro. The study wasplanned to be carried out in two stages. In the first stage, cell viability and cytotoxicity parameters werestudied using 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide and lactate dehydrogenaserelease assays, respectively, with human U87MG glioma and human PC3 prostate cancer cell cultures.In the second stage, to obtain a clear insight into the molecular events after exposing, we examined theeffects of selected $Y_2O_3$ nanoparticle on the expression of genes in U87MG and PC3 cell cultures using$RT^2$ Profiler PCR Arrays. $Y_2O_3$ nanoparticles have IC20 of 0,18 mg/L and 2,903 mg/L in PC3 andU87MG cell lines, respectively. $Y_2O_3$ nanoparticle induced up-regulation of 24 and down-regulation of22 genes in PC3 cells and up-regulation of 53 and down-regulation of 27 genes in U87MG cells. Thisstudy of gene expression profiles affected by nanotoxicity provides critical information for the clinicaland environmental applications of $Y_2O_3$ nanoparticles.

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Andelman T, Gordonov S, Busto G, Moghe PV, Riman RE, 2010. Synthesis and Cytotoxicity of Y2O3 Nanoparticles of Various Morphologies. Nanoscale Research Letters, 5: 263.
Appiahopong R, Commandeur J, Vanvugtlussenburg B, Vermeulen N, 2007. Inhibition of Human Recombinant Cytochrome P450s by Curcumin and Curcumin Decomposition Products. Toxicology 235 (1-2): 83–91.
Ashkenazi A, Salvesen G, 2014. Regulated Cell Death: Signaling and Mechanisms. Annual Review of Cell and Developmental Biology, 30 (1): 337–356.
Auffan M, Rose J, Bottero JY, Lowry GV, Jolivet JP, Wiesner MR, 2009. Towards a Definition of Inorganic Nanoparticles From an Environmental, Health and Safety Perspective. Nature Nanotechnology, 4: 634–641.
Aydın E, Türkez H, Hacımüftüoğlu F, Tatar A, Geyikoğlu F, 2017. Molecular Genetic and Biochemical Responses in Human Airway Epithelial Cell Cultures Exposed to Titanium Nanoparticles in Vitro. Journal of Biomedical Materials Research Part A, 105 (7): 2056–2064.
Bai C, Liu M, 2012. Implantation of Nanomaterials and Nanostructures on Surface and Their Applications. Nano Today, 7 (4): 258–281.
Bañobre-López M, Teijeiro A, Rivas J, 2013. Magnetic Nanoparticle-Based Hyperthermia for Cancer Treatment. R Reports of Practical Oncology & Radiotherapy, 18 (6): 397–400.
Chairuangkitti P, Lawanprasert S, Roytrakul S, Aueviriyavit S, Phummiratch D, Kulthong K, Chanvorachote P, Maniratanachot R, 2013. Silver Nanoparticles Induce Toxicity in A549 Cells Via ROS-dependent and ROSIndependent Pathways. Toxicology In Vitro, 27 (1): 330–338.
Chang M, Tie S, 2008. Fabrication of Novel Luminor Y2O3:Eu3$mathplus$@SiO2@YVO4:Eu3$mathplus$with Core/shell Heteronanostructure. Nanotechnology, 19 (7): 075711.
Cheng X, 1999. Synthesis of Nanometer-sized Yttrium Oxide Particles in Diisooctyl Sodium Sulphosuccinate/Isooctane Reverse Micelle Solution. Virginia Polytechnic Institute and State University, Master Thesis (Printed).
Costello LC, Franklin RB, 2000. The Intermediary Metabolism of the Prostate: A Key to Understanding the Pathogenesis and Progression of Prostate Malignancy. Oncology, 59:269–282.
Foldbjerg R, Dang DA, Autrup H, 2011. Cytotoxicity and genotoxicity of Silver Nanoparticles in The Human Lung Cancer Cell Line, A549. Archives of Toxicology, 85: 743–750.
Fotakis G, Timbrell JA, 2006. In Vitro Cytotoxicity Assays: Comparison of LDH, Neutral Red, MTT and Protein Assay in hepatoma Cell Lines Following Exposure to Cadmium Chloride. Toxicology Letters 160 (2): 171–177.
García-Perdomo HA, Correa-Ochoa JJ, Contreras-García R, Daneshmand S, 2018. Effectiveness of extended Pelvic Lymphadenectomy in the Survival of Prostate Cancer: A Systematic Review and meta-analysis. Central European Journal of Urology, 71 (3): 262–269.
Gaucher S, Jarraya M, 2015. Technical Note: Comparison of the PrestoBlue and LDH Release Assays with the MTT Assay for Skin Viability Assessment. Cell and Tissue Banking, 16: 325–329.
Goiato M, Freitas E, dos Santos D, de Medeiros R, Sonego M, 2015. Acrylic Resin Cytotoxicity for Denture Base: Literature Review. Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University, 24 (4): 679–686.
Hahn MA, Singh AK, Sharma P, Brown SC, Moudgil BM, 2011. Nanoparticles as Contrast Agents for in Vivo Bioimaging: Current Status and future Perspectives. Analytical and Bioanalytical Chemistry, 399: 3–27.
Hilger I, 2013. In vivo Applications of Magnetic Nanoparticle Hyperthermia. International Journal of Hyperthermia, 29: 828–834.
Hoseinnejad M, Jafari SM, Katouzian I, 2018. Inorganic and Metal Nanoparticles and Their Antimicrobial Activity in food Packaging Applications. Critical Reviews in Microbiology, 44 (2): 161–181.
Ianoş R, Băbuţă R, Lazău R, 2014. Characteristics of Y2O3 Powders Prepared by Solution Combustion Synthesis in the Light of a New Thermodynamic Approach. Ceramics International, 40 (8-Part A): 12207–12211.
Kennedy IM, Wilson D, Barakat AI, 2009. Uptake and Inflammatory Effects of Nanoparticles in a Human Vascular Endothelial Cell Line. Research Report (Health Effects Institute), 136: 3–32.
Khandrika L, Kumar B, Koul S, Maroni P, Koul HK, 2009. Oxidative Stress in Prostate Cancer. Cancer Letters 282 (2): 125–136.
Kilbourn BT, 1994. Yttrium oxide. In: Bloor D, Brook RJ, Flemings MC, Mahajan S (Ed) The Encyclopedia of Advanced Materials, Pergamon Press, No: 4, pp. 2957–2959, Oxford.
Kim J, Piao Y, Hyeon T, 2009. Multifunctional Nanostructured Materials for Multimodal Imaging, and Simultaneous Imaging and Therapy. Chemical Society Reviews, 38: 372–390.
Kim JH, Kim CS, Ignacio RMC, Kim DH, Sajo MEJ, Maeng EH, Qi XF, Park SE, Kim YR, Kim MK, Lee KJ, Kim SK, 2016. Immunotoxicity of Silicon Dioxide Nanoparticles with Different Sizes and Electrostatic Charge. International Journal of Nanomedicine, 9 (2): 183–193.
Kurfurstova D, Bartkova J, Vrtel R, Alena Mickova, Alena Burdova, Dusana Majera, Martin Mistrik, Milan Kral, Frederic R. Santer, Jan Bouchal, Jiri Barte, 2016. DNA Damage Signalling Barrier, Oxidative Stress and Treatment-Relevant DNA Repair Factor Alterations During Progression of Human Prostate Cancer. Molecular Oncology, 10 (6): 879–894.
Lam CW, James JT, McCluskey R, Hunter RL, 2004. Pulmonary Toxicity of Single-Wall Carbon Nanotubes in Mice 7 and 90 Days After Intratracheal Instillation. Toxicological Sciences 77 (1): 126–134.
Laurent S, Forge D, Port M, Roch A, Robic C, Elst LV, Muller RN, 2008. Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications. Chemical Reviews, 108 (6), 2064–2110.
Lewinski N, Colvin V, Drezek R, 2008. Cytotoxicity of Nanoparticles. Small 4 (1): 26–49.
Li J, Zhu Y, Wang H, Ji X, 2018. Targeting Long Noncoding RNA in Glioma: A Pathway Perspective. Molecular Therapy - Nucleic Acids 13: 431–441.
Li XZ, Kim S, Cho W, Lee SY, 2013. Optical Detection of Nanoparticle-Enhanced Human Papillomavirus Genotyping Microarrays. Biomedical Optics Express 4 (2): 187-192.
Lomelino CL, Andring JT, McKenna R, Kilberg MS, 2017. Asparagine synthetase: Function, Structure, and Role in Disease. Journal of Biological Chemistry, 292 (49): 19952-19958.
Long TC, Saleh N, Tilton RD, Lowry GV, Veronesi B, 2006. Titanium dioxide (P25) Produces Reactive Oxygen Species in Immortalized Brain Microglia (BV2): Implications for Nanoparticle Neurotoxicity. Environmental Science & Technology 40 (14): 4346–4352.
Lu S, Zhang W, Zhang R, Liu P, Wang Q, Shang Y, Wu M, Donaldson K, Wang Q, 2015. Comparison of cellular Toxicity Caused by ambient Ultrafine Particles and Engineered Metal Oxide Nanoparticles. Particle and Fibre Toxicology, 12: 5.
Ma W, Jing L, Valladares A, Mehta SL, Wang Z, Li PA, Bang JJ, 2015. Silver Nanoparticle Exposure Induced Mitochondrial Stress, Caspase-3 Activation and Cell Death: Amelioration by Sodium selenite. International Journal of Biological Sciences, 11 (8): 860–867.
Manke A, Wang L, Rojanasakul Y, 2013. Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity. BioMed Research International, 2013: 1–15.
Maurer-Jones MA, Gunsolus IL, Murphy CJ, Haynes CL, 2013. Toxicity of Engineered Nanoparticles in the Environment. Analytical Chemistry 85 (6): 3036–3049.
Medina C, Santos‐Martinez MJ, Radomski A, Corrigan OI, Radomski MW, 2007. Nanoparticles: Pharmacological and Toxicological Significance. British Journal Pharmacology, 150 (5): 552–558.
Meunier B, de Visser SP, Shaik S, 2004. Mechanism of Oxidation Reactions Catalyzed by Cytochrome P450 Enzymes. Chemical Reviews 104 (9): 3947–3980.
Morandi GD, Wiseman SB, Guan M, Zhang XW, Martin JW, Giesy JP, 2017. Elucidating Mechanisms of Toxic Action of Dissolved Organic Chemicals in Oil Sands Process-Affected Water (OSPW). Chemosphere 186: 893–900.
Nagajyothi PC, Pandurangan M, Veerappan M, Doo HK, Sreekanth TVM, Shim J, 2018. Green Synthesis, Characterization and Anticancer Activity of Yttrium oxide Nanoparticles. Materials Letters, 216: 58–62.
Ohgaki H, Kleihues P, 2009. Genetic Alterations and Signaling Pathways in The Evolution of Gliomas. Cancer Science 100 (12): 2235–2241.
Olmos-Alonso A, Schetters STT, Sri S, Askew K, Mancuso R, Vargas-Caballero M, Holscher C, Perry VH, GomezNicola D, 2016. Pharmacological Targeting of CSF1R Inhibits Microglial Proliferation and Prevents The Progression of Alzheimer’s-Like Pathology. Brain 139 (3): 891–907.
Pezaro C, Woo HH, Davis ID (2014) Prostate Cancer: Measuring PSA. Internal Medicine Journal, 44 (5): 433–440.
Schubert D, Dargusch R, Raitano J, Chan S-W (2006) Cerium and Yttrium oxide Nanoparticles are Neuroprotective. Biochemical and Biophysical Research Communications, 342 (1): 86–91.
Selvaraj V, Bodapati S, Murray E, Rice KM, Winston N, Shokuhfar T, Zhao Y, Blough E, (2014) Cytotoxicity and Genotoxicity Caused by Yttrium oxide Nanoparticles in HEK293 Cells. International Journal Nanomedicine 9:1379–1391.
Shah PV, Rajput SJ, 2018. Facile Synthesis of Chitosan Capped Mesoporous Silica Nanoparticles: A pH Responsive Smart Delivery Platform for Raloxifene Hydrochloride. AAPS Pharm SciTech, 19: 1344–1357.
Siddiqui MA, Alhadlaq HA, Ahmad J, Al-Khedhairy AA, Musarrat J, Ahamed M, 2013. Copper Oxide Nanoparticles Induced Mitochondria Mediated Apoptosis in Human Hepatocarcinoma Cells. PLoS ONE 8 (8): e69534.
Siegel RL, Miller KD, Jemal A, 2017. Cancer statistics, 2017. CA: A Cancer Journal for Clinicians, 67 (1): 7–30.
Sönmez E, Türkez H, Aydın E, Özgeriş FB, Öztetik E, Kerli S, Cacciatore I, Di Stefano A, 2015. Hepatic Effects of Yttrium oxide Nanoflowers: In Vitro Risk Evaluation. Toxicological & Environmental Chemistry 97 (5): 599– 608.
Soto KF, Carrasco A, Powell TG, Garza KM, Murr LE, 2005. Comparative In Vitro Cytotoxicity Assessment of Some Manufactured Nanoparticulate Materials Characterized by Transmissionelectron Microscopy. Journal of Nanoparticle Research 7:145–169.
Stepanenko AA, Dmitrenko VV, 2015. Pitfalls of The MTT Assay: Direct and Off-Target Effects of Inhibitors Can Result in over/underestimation of cell viability. Gene 574 (2):193–203.
Sun J, Wang S, Zhao D, Hun FH, Weng L, Liu H, 2011. Cytotoxicity, Permeability, and Inflammation of Metal oxide Nanoparticles in Human Cardiac Microvascular Endothelial Cells. Cell Biology Toxicology 27:333–342.
Tiwari JN, Tiwari RN, Kim KS, 2012. Zero-dimensional, One-Dimensional, Two-Dimensional and Three-Dimensional Nanostructured Materials for Advanced Electrochemical Energy Devices. Progress in Materials Science 57 (4): 724–803.
Van Meerloo J, Kaspers GJL, Cloos J, 2011. Cell Sensitivity Assays: The MTT Assay. In: Cree IA (ed) Cancer Cell Culture. Humana Press, pp. 237–245, NJ, Totowa,
Vandebriel RJ, De Jong WH, 2012. A Review of Mammalian Toxicity of ZnO Nanoparticles. Nanotechnology, Science and Applications, 5: 61–71.
Veiseh O, Gunn JW, Zhang M, 2010. Design and Fabrication of Magnetic Nanoparticles for Targeted Drug Delivery and Imaging. Design and Fabrication of Magnetic Nanoparticles for Targeted Drug Delivery and Imaging, 62 (3): 284–304.
Wahab R, Siddiqui MA, Saquib Q, Dwivedi S, Ahmad J, Musarrat J, Al-Khedhairy AA, Shinc HS, 2014. ZnO Nanoparticles Induced Oxidative Stress and Apoptosis in HepG2 and MCF-7 Cancer Cells and Their Antibacterial Activity. Colloids Surf B Biointerfaces, 117: 267–276.
Weant MP, Jesús CM-D, Yerram P, 2018. Immunotherapy in Gliomas. Seminars in Oncology Nursing, 34 (5):501– 512.
Wong BSE, Hu Q, Baeg GH, 2017. Epigenetic Modulations in Nanoparticle-Mediated Toxicity. Food Chemical Toxicology 109 (Part 1): 746–752.
Woo TH, 2016. Feasibility Study for Radiation Therapy Using Nano-Robotics Incorporated with Three-Dimensional (3D) Printing. Rendiconti Lincei, 27: 721–728.
Yu K-N, Chang S-H, Park SJ, Lim J, Lee J, Yoon TJ, Kim JS, Cho MH, 2015. Titanium dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells. PLOS One, 10: e0131208.
Zhang C, Li C, Peng C, Chai R, Huang S, Yang D, Cheng Z, Lin J, 2010. Facile and Controllable Synthesis of Monodisperse $CaF_2$ and $CaF_2$:$Ce^{3+}$/$Tb^{3+}$ Hollow Spheres as Efficient Luminescent Materials and Smart Drug Carriers. Chemistry —A European Journal, 16 (19): 5672–5680.
Zheng X, Wu R, Chen Y, 2011. Effects of ZnO Nanoparticles on Wastewater Biological Nitrogen and Phosphorus Removal. Environmental Science & Technology, 45 (7): 2826–2832.
Zhou G, Li Y, Ma Y, Liu Z, Cao L, Wang D, Liu S, Xu We, Wang W, 2016. Size-dependent Cytotoxicity of Yttrium Oxide Nanoparticles on Primary Osteoblasts in vitro. Journal of Nanoparticle Research 18:135.