Borik Asitin 8305C Anaplastik Tiroit Kanseri Hücrelerinde Antioksidan ve Anti-kanser Aktivitesi

Year 2021, Volume: 10 Issue: 2, 213 - 221, 28.06.2021

Melike Ersöz

https://doi.org/10.37989/gumussagbil.834614

Cited By: 2

Abstract

Bu çalışmanın amacı, borik asitin 8305C insan anaplastik tiroit kanseri (ATK) hücrelerinde sitotoksik, anti-proliferatif, apoptotik ve antioksidan etkilerini değerlendirmektir. Borik asitin sitotoksisitesi 0-1000 μg/mL doz aralığında (24, 48 ve 72 saat) 8305C insan ATK hücrelerinde bir tetrazolyum testiyle (MTT) belirlendi. Hücrelerdeki proliferasyon ve apoptoz incelendi. Biyokimyasal parametreler spektrofotometrik olarak tespit edildi. 24, 48 ve 72 saat borik asit ile muamele edilen 8305C insan ATK hücrelerinin yarı-maksimum inhibisyon konsantrasyon (IC50) değerleri sırasıyla 238 µg/mL, 116 µg/mL ve 70 µg/mL olarak hesaplandı (p<0,05). Prolifere olan hücre çekirdek antijeni (PCNA) pozitif hücrelerin yüzdesi 200, 250, 300 µg/mL konsantrasyonda borik asit ile 48 saat muamele edilen hücrelerde anlamlı azalma gösterdi (p<0,01). Borik asitin 250 ve 300 µg/mL konsantrasyonlarında 24 ve 48 saatlik muamelesi, kontrol hücrelerine kıyasla 8305C ATK hücrelerinde apoptotik hücre sayısında anlamlı artış gösterdi (p<0,01). En düşük malondialdehit seviyesi 48 saat 300 µg/mL konsantrasyonda uygulanan hücrelerde saptandı (p<0,01). En yüksek süperoksit dismutaz aktivitesi 48 saat 250 µg/mL borik asit uygulanan hücrelerde olurken (p<0,01), glutatyon seviyesi 300 µg/mL borik asit uygulanan hücrelerde kontrol hücrelerine göre anlamlı olarak arttı (p<0,05). Bu çalışma ile elde edilen sonuçlar, borik asitin 8305C insan ATK hücrelerinde anti-proliferatif ve apoptotik aktiviteye sahip umut verici yeni bir terapötik ajan olabilirliğini gösterir. Çalışma in vivo deneylerle desteklenmelidir.

Keywords

Apoptoz, Borik Asit, Kanser, Proliferasyon, Troit.

Thanks

Çalışma sürecinde katkılarından dolayı Doç. Dr. Banu Mansur’a, Gülşah Akbaş’a ve Fatma Şayan Poyraz’a teşekkür ederim.

Antioxidant and Anti-cancer Activity of Boric Acid in 8305C Anaplastic Thyroid Cancer Cells

Abstract

anti-proliferative, apoptotic and antioxidant effects of boric acid in 8305C human anaplastic thyroid cancer (ATC) cells. The cytotoxicity of boric acid was determined at a dose range of 0-1000 μg/mL in the human ATC cells (24, 48, and 72 hours) by a tetrazolium test (MTT). Proliferation and apoptosis in the cells were examined. Biochemical parameters were determined spectrophotometrically. The half-maximal inhibitory concentration (IC50) values of cells treated with boric acid for 24, 48, and 72 hours were calculated as 238 µg/mL, 116 µg/mL, and 70 µg/mL, respectively (p<0.05). The percentage of proliferating cell nuclear antigen (PCNA) positive cells showed a significant decrease in the cells treated with boric acid at 200, 250, and 300 µg/mL concentrations for 48 hours (p<0.01). Boric acid administered at 250 and 300 µg/mL showed a significant increase in the percentage of apoptotic cells of 8305C ATC cells compared to control cells (p<0.01). The lowest malondialdehyde level was detected in cells treated with boric acid at 300 µg/mL for 48 hours (p<0.01). While the highest superoxide dismutase level was in cells treated with 250 µg/mL boric acid for 48 hours (p<0.01), glutathione level increased significantly in cells treated with 300 µg/mL boric acid compared to control cells (p<0.05). The results obtained from this study demonstrate that boric acid can be a promising new therapeutic agent in terms of anti-proliferative and apoptotic activities in 8305C human ATC cells. The study should be supported by in vivo experiments.

Keywords

Apoptosis, Boric Acid, Cancer, Proliferation, Thyroid.

References

• 1. Molinaro, E, Romei, C, Biagini, A, Sabini, E, Agate, L, Mazzeo, S, Materazzi, G, Sellari-Franceschini, S, Ribechini, A, Torregrossa, L, Basolo, F, Vitti, P. and Elisei, R. (2017). “Anaplastic Thyroid Carcinoma: From Clinicopathology to Genetics and Advanced Therapies”. Nature Reviews Endocrinology, 13, 644–660.
• 2. Saini, S, Tulla, K, Maker, A.V, Burman, K.D. and Prabhakar, B.S. (2018). “Therapeutic Advances in Anaplastic Thyroid Cancer”. Molecular Cancer, 17 (1), 154-168.
• 3. Smallridge, R.C, Ain, K.B, Asa, S.L, Bible, K.C, Brierley, J.D, Burman, K.D, Kebebew, E, Lee, N.Y, Nikiforov, Y.E, Rosenthal, M.S, Shah, M.H, Shaha, A.R. and Tuttle, R.M. (2012). “American Thyroid Association Anaplastic Thyroid Cancer Guidelines Taskforce”. Practice Guideline Thyroid, 22 (11), 1104-1139.
• 4. Ito, T, Seyama, T, Hayashi, Y, Hayashi, T, Dohi, K, Mizuno, T, Iwamoto, K, Tsuyama, N, Nakamura, N. and Akiyama, M. (1994). “Establishment of 2 Human Thyroid-Carcinoma Cell-Lines (8305C, 8505C) Bearing p53 Gene-Mutations”. International Journal of Oncology, 4 (3), 583-586.
• 5. Nadi, S, Monfared, AS, Zabihi, E, Mahmoudzadeh, A, Eyvazzadeh, N. ve Tahamtan, R. (2019). “Combined Effect of Iodine Contrast Media, Cisplatin and External Beam Radiotherapy on Anaplastic Thyroid Cancer Cells”. Journal of Biomedical Physics and Engineering, 9 (2), 217-226.
• 6. Bilgiç, M. ve Dayık, M. (2013). “Borun Özellikleri ve Tekstil Endüstrisinde Kullanımıyla Sağladığı Avantajlar”. Tekstil Teknolojileri Elektronik Dergisi, 7 (2), 27-37.
• 7. Baker, S.J, Tomsho, J.W. and Benkovic, S.J. (2011). “Boron-Containing Inhibitors of Synthetases”. Chemical Society Reviews, 40 (8), 4279–4285.
• 8. Devirian, T.A. and Volpe, S.L. (2003). “The Physiological Effects of Dietary Boron”. Critical Reviews in Food Science and Nutrition, 43 (2), 219–231.
• 9. Marsiccobetre, S, Rodríguez-Acosta, A, Lang, F, Figarella, K. and Uzcátegui, N.L. (2017). “Aquaglyceroporins are The Entry Pathway of Boric Acid in Trypanosoma Brucei”. Biochimica et Biophysica Acta Biomembranes, 1859 (5), 679-685.
• 10. Hakki, S.S, Bozkurt, B.S. and Hakki, E.E. (2010). “Boron Regulates Mineralized Tissue-Associated Proteins in Osteoblasts (MC3T3-E1)”. Journal of Trace Elements in Medicine and Biology, 24, 243–250.
• 11. Barranco, W.T. and Eckhert, C.D. (2006). “Cellular Changes in Boric Acid-Treated DU-145 Prostate Cancer Cells”. British Journal of Cancer, 94, 884–890.
• 12. Movahedi Najafabadi, B.H. and Abnosi, M.H. (2016). “Boron İnduces Early Matrix Mineralization Via Calcium Deposition and Elevation of Alkaline Phosphatase Activity in Differentiated Rat Bone Marrow Mesenchymal Stem Cells”. Cell Journal, 18 (1), 62–73.
• 13. Iztleuov, M, Umirzakova, Z, Sambaeva, S, Yesmukhanova, D, Akhmetova, A, Medeuova, R, Kolıshbaeva, I. and Iztleuov, E. (2017). “The Effect of Chromium and Boron on the Lipid Peroxidation and Antioxidant Status (in Experiment)”. BioTechnology Indian Journal, 13 (1), 125-132.
• 14. Türkeza, H, Geyikoglu, F, Tatar, A, Keles, S. and Özkan, A. (2007). “Effects of Some Boron Compounds on Peripheral Human Blood”. Zeitschrift für Naturforschung. C, A Journal of Biosciences, 62, 889–896.
• 15. Barranco, W.T. and Eckhert, C.D. (2004). “Boric Acid Inhibits Human Prostate Cancer Cell Proliferation”. Cancer Letters, 216 (1), 21-29.
• 16. Scorei, R.I. and Popa, R. (2010). “Boron-Containing Compounds as Preventive and Chemotherapeutic Agents for Cancer”. Anti-Cancer Agents in Medicinal Chemistry, 10 (4), 346-351.
• 17. Nikkhah, S. and Naghii, M.R. (2017). “Using Boron Supplementation in Cancer Prevention and Treatment”. The Cancer Press, 3 (3), 113-119.
• 18. Kane, R.C, Bross, P.F, Farrell, A.T. and Pazdur, R. (2003). “Velcade((R)): USFDA Approval for The Treatment of Multiple Myeloma Progressing on Prior Therapy”. The Oncologist, 8 (6), 508–513.
• 19. Uluisik, I, Karakaya, H.C. and Koc, A. (2018). “The Importance of Boron in Biological Systems”. Journal of Trace Elements in Medicine and Biology, 45, 156-162.
• 20. Walker, J.M. (2002). The Protein Protocols Handbook. Totowa: Humana Press.
• 21. Esterbauer, H. and Cheeseman, K.H. (1990). “Determination of Aldehydiclipid Peroxidation Products: Malonaldehyde and 4-hydroxyno-nenal”. Methods in Enzymology, 186, 407–421.
• 22. McCord, J.M. and Fridovich, I. (1969). “Superoxide Dismutase an Enzymic Function for Erythrocuprein (hemocuprein)”. The Journal of Biological Chemistry, 244, 6049–6055.
• 23. Boyne, A.F. and Ellman, G.L. (1972). “A Methodology for Analysis of Tissue Sulfhydryl Components”. Analytical Biochemistry, 46, 639–653.
• 24. Hacioglu, C, Kar, F, Kacar, S, Sahinturk, V. and Kanbak, G. (2020). “High Concentrations of Boric Acid Trigger Concentration-Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line”. Biological Trace Element Research, 193 (2), 400-409. https://doi.org/ 10.1007/s12011-019-01739-x.
• 25. Acerbo, A.S. and Miller, L.M. (2009). “Assessment of the Chemical Changes Induced in Human Melanoma Cells by Boric Acid Treatment Using Infraredimaging”. The Analyst, 134, 1669-1674.
• 26. Evan, G.I. and Vousden, K.H. (2001). “Proliferation, Cell Cycle and Apoptosis in Cancer”. Nature, 411, 342-348.
• 27. Bologna-Molina, R, Mosqueda-Taylor, A, Molina-Frechero, N, Mori-Estevez, A.D. and Sánchez-Acuña, G. (2013). “Comparison of the Value of PCNA and Ki-67 as Markers of Cell Proliferation in Ameloblastic Tumors”. Medicina Oral, Patología Oral Y Cirugía Bucal, 18 (2), 174-179.
• 28. Kyrylkova, K, Kyryachenko. S, Leid, M. and Kioussie, C. (2012). “Detection of Apoptosis by TUNEL Assay”. Methods in Molecular Biology, 887, 41-47.
• 29. Barranco, W.T, Kim, D.H, Stella, S.R. and Eckhert, C.D. (2009). “Boric Acid İnhibits Stored Ca2+ Release in DU-145 Prostate Cancer Cells”. Cell Biology and Toxicology, 25 (4), 309–320.
• 30. Cui, Y, Winton, M.I, Zhang, Z.F, Rainey, C, Marshall, J, De Kernion, J.B. and Eckhert, C.D. (2004). “Dietary Boron Intake and Prostate Cancer Risk”. Oncology Reports, 11 (4), 887–892.
• 31. Khoshtabiat, L, Mahdavi, M, Dehghan, G. and Rashidi, M.R. (2016). “Oxidative Stress-Induced Apoptosis in Chronic Myelogenous Leukemia K562 Cells by an Active Compound from the Dithio- Carbamate Family”. Asian Pacific Journal of Cancer Prevention, 17 (9), 4267-4273.
• 32. Tandon, V.R, Sharma, S, Mahajan, A. and Bardi, G.H. (2005). “Oxidative Stress: A Novel Strategy in Cancer Treatment”. Journal of Cancer Therapy, 7 (1), 1-3.
• 33. Ince, S, Kucukkurt, I, Cigerci, I.H, Fidan, A.F. and Eryavuz, A. (2010). “The Effects of Dietary Boric Acid and Borax Supplementation on Lipid Peroxidation, Antioxidant Activity, and DNA Damage in Rats”. Journal of Trace Elements in Medicine and Biology, 24 (3), 161-164.
• 34. Valko, M, Leibfritz, D, Monco, l.J, Cronin, M.T.D, Mazur, M. and Telser, J. (2007). “Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease”. The International Journal of Biochemistry & Cell Biology, 39, 44–84.
• 35. Morry, J, Ngamcherdtrakul, W. and Yantasee, W. (2017). “Oxidative Stress in Cancer and Fibrosis: Opportunity for Therapeutic Intervention with Antioxidant Compounds, Enzymes, and Nanoparticles”. Redox Biology, 11, 240–253.
• 36. Aslankoc, R, Demirci, D, Inan, U, Yildiz, M, Ozturk, A, Cetin, M, Savran, E.S. and Yilmaz, B. (2019). “The Role of Antioxidant Enzymes in Oxidative Stress-Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPx)”. Medical Journal of Suleyman Demirel University, 26 (3), 362-369.