Yıl: 2017 Cilt: 6 Sayı: 1 Sayfa Aralığı: 38 - 54 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ

Öz:
Metal temelli bileşikler potansiyel etkilerinden ve az toksisiteye neden olduklarından dolayı uzun zamandır kullanılmaktadır. Metal bileşik sisplatin çeşitli kanser türlerine karşı tıbbi olarak kullanılmış ve yan etkiler göstermiştir. Bu çalışmada sisplatine alternatif ajan olarak düşünülen titanyum dioksitin A549 hücreleri üzerindeki etkileri ve apoptotik mekanizması araştırıldı. Titanyum dioksitin 24, 48 ve 72 saatlik sürelerdeki zamana ve konsantrasyon aralığına bağlı olarak antiproliferatif etkileri MTT canlılık analizi kullanılarak belirlendi. Titanyum dioksitin apoptozisi tetiklediği saptandı. Titanyum dioksitin IC30konsantrasyonu, 72 saat süresince A549 hücreleri üzerinde uygulandığında erken ve geç apoptozisi tetiklediği belirlendi. Titanyum dioksitin IC30 konsantrasyonu, 72 saat süresince A549 hücreleri üzerine uygulandığında mitokondriyal membran potansiyelini azaltarak apoptozisi tetiklediği gösterildi. Buna rağmen kaspaz-3 aktivitesi gözlenmedi. Titanyum dioksitin IC30konsantrasyonun 72 saatlik süre sonundaki hematoksilen ve eozin, TUNEL, BrdU, Bcl-2 ve Bax immünositokimyasal analizleri sonucunda apoptotik indekslerinde artış belirlendi. Titanyum dioksitin IC30 konsantrasyonun uygulandığı A549 hücrelerinde 72 saatlik süre sonunda konfokal ve TEM mikroskobisi kullanılarak çeşitli apoptotik yapılar gözlendi. Bu sonuçlar titanyum dioksitin A549 hücreleri üzerinde antiproliferatif ve apoptotik etkilerini ve sisplatine eş potansiyel kemoterapötik bir ajan olabileceğini göstermektedir
Anahtar Kelime:

THE APOPTOTIC EFFECTS OF TITANIUM DIOXIDE ON A549 CELLS

Öz:
Metal-based compounds have been used for a long time because of their potential effects and low toxicity. Metal compound cisplatin has been used medically against various types of cancer and has shown side effects. In present study, we researched the effects of titanium dioxide, which is considered as an alternative agent against cisplatin on the A549 cells and its apoptotic mechanism were investigated. The antiproliferative effects of titanium dioxide were determined using MTT viability analysis depending on the time and concentration intervals at 24, 48 and 72 hours. We assessed that titanium dioxide induced apoptosis. The IC30 concentration of titanium dioxide triggered early and late apoptosis for 72 hours in A549 cells. The IC30 concentration of titanium dioxide was shown to induce apoptosis by reducing mitochondrial membrane potential for 72 hours. However, caspase-3 activity was not observed. The IC30 concentration of titanium dioxide revealed an increase in apoptotic index with immunocytochemical analysis of hematoxylin and eosin, TUNEL, BrdU, Bcl-2 and Bax for 72 hours. The apoptotic structures were scanned by using confocal and TEM microscopy in A549 cells for 72 hours. These results show that titanium dioxide induce antiproliferative and apoptotic effects on A549 cells and that titanium dioxide may be a potential chemotherapeutic agent like cisplatin
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • Desoize B. Cancer and metals and metal compounds. Crit Rev Oncol Hematol 2002; 42, 213-215.
  • Warra AA. Transition metal complexes and their application in drugs and cosmetics. J Chem Pharm Res 2011; 3(4):951-958.
  • Rafique S, Idrees M, Nasim A, Akbar H, Athar A. Transition metal complexes as potential therapeutic agents. Biotechnol. Mol Biol Rev 2010;5(2), pp. 38-45.
  • Florea AM, Büsselberg, D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 2011;3, 1351-1371.
  • Laine AL, Passirani C. Novel metal-based anticancer drugs: a new challenge in drug delivery. Curr Opin Pharmacol2012;12:420-426.
  • Devanand Venkatasubbu G, Ramasamy S, Ramakrishnan V, Kumar J. Folate targeted PEGylated titanium dioxide nanoparticles as a nanocarrier for targeted paclitaxel drug delivery. Adv Powder Technol2013,xxx, xxx-xxx.
  • Lazau C, Mocanu L, Miron I, Sfirloaga P, Tanasie G, Tatu C, Gruia A, Grozescu I. Consideration regarding the use of TiO2 doped nanoparticles in medicine. Dig J Nanomater Bios 2007; 2, 3, p. 257 - 263.
  • Subbarayan Periasamy V, Athinarayanan J, Al-Hadi AM, Juhaimi FA, Mahmoud MH, Alshatwi AA. Identification of titanium dioxide nanoparticles in food products: Induce intracellular oxidative stress mediated by TNF and CYP1A genes in human lung fibroblast cells. Environ Toxicol Pharmacol 2015;39, 176-186.
  • Chen T, Yan J, Li Y. Genotoxicity of titanium dioxide nanoparticles. J Food Drug Anal 2014; 22, 95-104.
  • Fujishima A, Honda K. Electrochemical photolysis of water at a semiconductor electrode. Nature,1972; 238, 37.
  • Lai TY, Lee WC. Killing of cancer cell line by photoexcitation of folic acid-modified titanium dioxide nanoparticles. J Photochem Photobiol A Chem 2009;204, 148-153.
  • Kubota Y, Shuin T, Kawasaki C, Hosaka M, Kitamura H, Cai R, Sakai H, Hashimoto K, Fujishima A. Photokilling of T-24 human bladder cancer cells with titanium dioxide. Br J Cancer 1994;70, 1107 - 1111.
  • Xu J, Sun Y, Huang J, Chen C, Liu G, Jiang Y, Zhao Y, Jiang Z. Photokilling cancer cells using highly cell-specific antibody-TiO(2) bioconjugates and electroporation. Bioelectrochemistry 2007;71(2):217-22.
  • Bruin EC, Medema JP. Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev 2008;34, 737- 749.
  • Gopinath P, Kumar Gogoi S, Sanpuii P, Paul A, Chattopadhyay A, Sankar Ghosh S. Signaling gene cascade in silver nanoparticle induced apoptosis. Colloids Surf B Biointerfaces 2010;77, 240-245.
  • Indran IR, Tufo G, Pervaiz S, Brenner C. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim Biophys Acta 2011;1807,735-745.
  • Wong RSY. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011;30:87.
  • Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, Parks WP. In vitro cultivation of human tumors: Establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 1973;51 (5): 1417-23.
  • Çiftçi Akalın G, İşcan A, Kutlu HM. Escin reduces cell proliferation and induces apoptosis on glioma and lung adenocarcinoma cell lines. Cytotechnology 2015;67:893-904.
  • Kaplan A, Çiftçi Akalın G, Kutlu HM. Melatonin induces antiproliferative activity through modulation of apoptotic pathway in H-ras oncogene transformed 5RP7 cells. Turk J Biol 2015;39: 879- 887.
  • Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: New insights into their cellular reduction. Biotechnol Annu Rev 2005;11. 127-152.
  • Chiba K, Kawakami K, Tohyama K. Simultaneous evaluation of cell viability by neutral red, MTT and crystal violet staining assays of the same cells. Toxicol In Vitro 1998;12, 251-258.
  • Hingorani R, Deng J, Elia J, Mclntyre C, Mittar D. Detection of Apoptosis Using the BD Annexin V FITC Assay on the BD FACSVerse(TM) System, BD Biosciences.2011.
  • Jiang C, Wang Z, Ganther H, Lu J. Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells. Cancer Res 2001;61, 3062-3070.
  • Ly JD, Grubb DR and Lawen A. The mitochondrial membrane potential (??m) in apoptosis; an update. Apoptosis 2003;8, 115-128.
  • Marchetti C, Jouy N, Leroy-Martin B, Defossez A, Formstecher P, Marchetti P. Comparison of four fluorochromes for the detection of the inner mitochondrial membrane potential in human spermatozoa and their correlation with sperm motility. Hum Reprod 2004;19, 10 pp. 2267-2276.
  • Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and Eosin Staining of Tissue and Cell Sections. Basic Methods in Microscopy, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA, 2006.
  • Plastina P, Bonofiglio D, Vizza D, Fazio A, Rovito D, Giordano C, Barone I, Catalano S, Gabriele B. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol 2012;140, 325- 332.
  • Santini D, Tonini G, Vecchio FM, Borzomati D, Vincenzi B, Valeri S, Antinori A, Castri F, Coppola R, Magistrelli P, Nuzzo G, Picciocchi A. Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma. J Clin Pathol 2005;58:159-165.
  • Lagopati N, Kitsiou PV, Kontos AI, Venieratos P, Kotsopoulou E, Kontos AG, Dionysiou DD, Pispas S, Tsilibary EC, Falaras P. Photo-induced treatment of breast epithelial cancer cells using nanostructured titanium dioxide solution. J Photochem Photobiol A Chem 2010; 214, 215-223.
  • Stefanou E, Evangelou A, Falaras P. Effects of UV-irradiated titania nanoparticles on cell proliferation, cancer metastasis and promotion. Catal Today 2010;151(1-2):58-63.
  • Shavit M, Peri D, Melman A, Tshuva EY. Antitumor reactivity of non-metallocene titanium complexes of oxygen-based ligands: is ligand lability essential. J Biol Inorg Chem 2007;12:825-830.
  • Cengiz E, Wissing SA, Müller RH, Yazan Y. Sunblocking efficiency of various TiO2- loaded solid lipid nanoparticle formulations. Int J Cosmet Sci 2006;28, 371-378.
  • Thurn KT, Arora H, Paunesku T, Wu A, Brown EMB, Doty C, Kremer J, Woloschak G. Endocytosis of titanium dioxide nanoparticles in prostate cancer PC-3M cells. Nanomed Nanotechnol Bio Med 2011;7, 123-130.
  • Harada Y, Ogawa K, Irie Y, Endo H, Ferik LB, Uemura T, Tachibana K. Ultrasound activation of TiO2 in melanoma tumors. J Control Release 2011;149, 190-195.
  • Yamaguchi S, Kobayashi H, Narita T, Kanehira K, Sonezaki S, Kubota Y, Terasaka S, Iwasaki Y. Novel photodynamic therapy using water-dispersed TİO2-polyethylene glycol compound: evaluation of antitumor effect on glioma cells and spheroids in vitro. J Photochem Photobiol 2010;86: 964-971.
  • Islam Md. S, Kusumoto Y, Abdulla- Al-Mamun Md, Horie Y. Photocatalytic and AC magnetic- field induced enhanced cytotoxicity of Fe3O4-TiO2 core-shell nanocomposites against HeLa cells. Catal Commun 2011;16, 39-44.
  • Chihara Y, Fujimoto K, Kondo H, Moriwaka Y, Sasahira T, Hirao Y, Kuniyasu H. Anti-Tumor effects of liposome-encapsulated titanium dioxide in nüde mice. Pathobiology 2007;74:353-358.
  • Murugan K, Dinesh D, Kavithaa K, Paulpandi M, Ponraj T, Alsalhi MS, Devanesan S, Subramaniam J, Rajaganesh R, Wei H, Kumar S, Nicoletti M, Benelli G. Hydrothermal synthesis of titanium dioxide nanoparticles: mosquitocidal potential and anticancer activity on human breast cancer cells (MCF-7). Parasitol Res 2016;3, 1085-1096.
APA Kaplan A, ÇİFTÇİ AKALIN G, KUTLU H (2017). TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. , 38 - 54.
Chicago Kaplan Ayşe,ÇİFTÇİ AKALIN Gülşen,KUTLU HATİCE MEHTAP TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. (2017): 38 - 54.
MLA Kaplan Ayşe,ÇİFTÇİ AKALIN Gülşen,KUTLU HATİCE MEHTAP TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. , 2017, ss.38 - 54.
AMA Kaplan A,ÇİFTÇİ AKALIN G,KUTLU H TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. . 2017; 38 - 54.
Vancouver Kaplan A,ÇİFTÇİ AKALIN G,KUTLU H TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. . 2017; 38 - 54.
IEEE Kaplan A,ÇİFTÇİ AKALIN G,KUTLU H "TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ." , ss.38 - 54, 2017.
ISNAD Kaplan, Ayşe vd. "TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ". (2017), 38-54.
APA Kaplan A, ÇİFTÇİ AKALIN G, KUTLU H (2017). TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. Anadolu Üniversitesi Bilim ve Teknoloji Dergisi :C-Yaşam Bilimleri ve Biyoteknoloji, 6(1), 38 - 54.
Chicago Kaplan Ayşe,ÇİFTÇİ AKALIN Gülşen,KUTLU HATİCE MEHTAP TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. Anadolu Üniversitesi Bilim ve Teknoloji Dergisi :C-Yaşam Bilimleri ve Biyoteknoloji 6, no.1 (2017): 38 - 54.
MLA Kaplan Ayşe,ÇİFTÇİ AKALIN Gülşen,KUTLU HATİCE MEHTAP TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. Anadolu Üniversitesi Bilim ve Teknoloji Dergisi :C-Yaşam Bilimleri ve Biyoteknoloji, vol.6, no.1, 2017, ss.38 - 54.
AMA Kaplan A,ÇİFTÇİ AKALIN G,KUTLU H TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. Anadolu Üniversitesi Bilim ve Teknoloji Dergisi :C-Yaşam Bilimleri ve Biyoteknoloji. 2017; 6(1): 38 - 54.
Vancouver Kaplan A,ÇİFTÇİ AKALIN G,KUTLU H TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ. Anadolu Üniversitesi Bilim ve Teknoloji Dergisi :C-Yaşam Bilimleri ve Biyoteknoloji. 2017; 6(1): 38 - 54.
IEEE Kaplan A,ÇİFTÇİ AKALIN G,KUTLU H "TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ." Anadolu Üniversitesi Bilim ve Teknoloji Dergisi :C-Yaşam Bilimleri ve Biyoteknoloji, 6, ss.38 - 54, 2017.
ISNAD Kaplan, Ayşe vd. "TİTANYUM DİOKSİTİN A549 HÜCRELERİ ÜZERİNDEKİ APOPTOTİK ETKİLERİ". Anadolu Üniversitesi Bilim ve Teknoloji Dergisi :C-Yaşam Bilimleri ve Biyoteknoloji 6/1 (2017), 38-54.