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5-Fluorourasil (5-FU) ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik ve Apoptotik Etkilerinin Araştırılması

Year 2020, Volume: 9 Issue: 2, 35 - 41, 30.12.2020
https://doi.org/10.46810/tdfd.796339

Abstract

Meme kanseri dünyanın hemen her bölgesinde kadınlar arasında en sık görülen kanser türüdür. Kansere bağlı ölümlerde akciğer kanserinden sonra ikinci sırada yer almaktadır. 5-Fluorourasil (5-FU) urasil ile aynı taşıma mekanizmasını kullanarak hücrelere girmeyi hedefleyen, hidrojenin yerine C-5 pozisyonunda bir flor atomu olan bir pirimidin analoğudur. C60 fulleren, antioksidan ve antitümör potansiyeli olan bir nanopartiküldür ve 5-FU’ya hücre tepkilerini modüle etmede faydalı olabilir. p53 proteini tümör gelişimini baskılayan bir transkripsiyon faktörü, TIGAR esas olarak glukoz metabolizmasının düzenleyicisi olarak işlev görür. Bu çalışmada 5-FU, C60 ve 5-FU+C60 kombinasyonunun MCF-7 insan meme kanseri hücreleri üzerindeki sitotoksik etkileri WST-1 analizi ile gerçekleştirildi. Ek olarak, DCFDA kullanılarak reaktif oksijen türleri düzeylerinin tespiti araştırıldı. Çalışmamızda zamana ve konsantrasyona bağlı olarak 5-FU’nun MCF-7 hücre canlılığını inhibe ettiği, C60 nanopartikülünün MCF-7 hücreleri üzerine tek başına uygulanması sonucunda anlamlı bir etkinin olmadığı görüldü. 5-FU+C60’ın birlikte kullanımının ise hücreler üzerinde sitotoksik etkisinin olduğu gösterildi. Öte yandan hücreler üzerine 5-FU, C60 ve 5-FU+C60 uygulamalarının ROS düzeylerinde anlamlı bir fark (artma ya da azalma) oluşturmadıkları belirlendi. İlaveten p53 ve TIGAR proteinlerinin ekspresyon düzeyleri Western Blot yöntemi ile incelenerek hücreler üzerindeki apoptotik etkileri araştırıldı. 5-FU ve 5-FU+C60 gruplarında p53 gen ekspresyonunun arttığı görüldü. 5-FU+C60 kombinasyonunun TIGAR ifadesini indükleyerek hücrelerin apoptoza gitmesine yardımcı olduğu gözlendi.

Supporting Institution

BÜBAP

Project Number

BAP-FEF.2017.00.017

Thanks

BAP-FEF.2017.00.017 nolu proje ile desteklediği için BÜBAP'a teşekkür ederiz.

References

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  • [5] Correia A, Silva D, Correia A, Vilanova M, Gärtner F, Vale N. Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations. Biomolecules. 2018; 8(4):175.
  • [6] Li Z, Pan LL, Zhang FL, Wang Z, Shen YY, Zhang ZZ. Preparation and characterization of fullerene (C60) amino acid nanoparticles for liver cancer cell treatment. Journal of Nanoscience and Nanotechnology. 2014;14 (6):4513-4518.
  • [7] Harhaji L, Isakovic A, Raicevic N, Markovic Z, Todorovic-Markovic B, Nikolic N, et al. Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. European Journal of Pharmacology. 2007;568(1-3):89-98.
  • [8] Green DR, Chipuk JE. p53 and metabolism: Inside the TIGAR. Cell. 2006;126(1): 30-32.
  • [9] Bensaad K, Tsuruta A, Selak MA, Vidal MNC, Nakano K, Bartrons R, et al. TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis. Cell. 2006;126(1):107-120.
  • [10] Pfeffer CM, Singh ATK. Apoptosis: A Target for anticancer therapy. International Journal of Molecular Sciences. 2018;19(2): 448.
  • [11] Temel Y, Taysi MŞ. The Effect of Mercury Chloride and Boric Acid on Rat Erythrocyte Enzymes. Biol Trace Elem Res. 2018:177-182.
  • [12] Temel Y, Koçyigit UM, Taysi MS, et al. Purification of glutathione S-transferase enzyme from quail liver tissue and inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3 (aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives on the enzyme activity. J Biochem Mol Toxicol. 2018; 32(3):e22034.
  • [13] Aybek H, Temel Y, Ahmed BM, Ağca CA, Çiftci M. Deciphering of the effect of chemotherapeutic agents on human glutathione S-transferase enzyme and MCF-7 cell line. Protein Pept. Lett. 2020;27:1-7.
  • [14] Liou GY, Storz P. Reactive oxygen species in cancer. Free Radical Research. 2010;44 (5):479-496.
  • [15] Yip NC, Fombon IS, Liu P, Brown S, Kannappan V, Armesilla AL, et al. Disulfiram modulated ROS–MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties. British Journal of Cancer. 2011;104(10):1564-1574.
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  • [17] Cai J, Chen S, Zhang W, Wei Y, Lu J, Xing J, et al. Proteomic analysis of differentially expressed proteins in 5-fluorouracil-treated human breast cancer MCF-7 cells. Clinical and Translational Oncology. 2014;16 (7):650-659.
  • [18] Ge ZH, Wang ZX, Yu TL, Yang N, Sun Y, Hao CL, et al. Morphine improved the antitumor effects on Mcf-7 cells in combination with 5-fluorouracil. Biomedicine & Pharmacotherapy. 2014;68(3):299-305.
  • [19] Wang F, Jin C, Liang H, Tang Y, Zhang H, Yang Y. Effects of Fullerene C60 Nanoparticles on A549 Cells. Environmental Toxicology and Pharmacology. 2014;37(2):656-661.
  • [20] Lynchak OV, Prylutskyy YI, Rybalchenko VK, Kyzyma OA, Soloviov D, Kostjukov VV, et al. Comparative analysis of the antineoplastic activity of C60 fullerene with 5-fluorouracil and pyrrole derivative in vivo. Nanoscale Research Letters. 2017;12(1):1-6.
  • [21] Raza K, Thotakura N, Kumar P, Joshi M, Bhushan S, Bhatia A, et al. C60-Fullerenes for delivery of docetaxel to breast cancer cells: A promising approach for enhanced efficacy and better pharmacokinetic profile. International Journal of Pharmaceutics. 2015;495(1):551-559.
  • [22] Hecht F, Pessoa CF, Gentile LB, Rosenthal D, Carvalho DP, Fortunato RS. The role of oxidative stress on breast cancer development and therapy. Tumor Biology. 2016;37(4):4281-4291.
  • [23] Valko M, Rhodes C, Moncol J, Izakovic MM, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions. 2006;160(1):1-40.
  • [24] Focaccetti C, Bruno A, Magnani E, Bartolini D, Principi E, Dallaglio K, et al. Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PLoS One. 2015;10(2):e0115686.
  • [25] Suzuki S, Okada M, Shibuya K, Seino M, Sato A, Takeda H, et al. JNK suppression of chemotherapeutic agents-ınduced ROS confers chemoresistance on pancreatic cancer stem cells. Oncotarget. 2015;6(1):458-470.
  • [26] Darsigny M, Babeu JP, Seidman EG, Gendron FP, Levy E, Carrier J, et al. Hepatocyte nuclear factor-4α promotes gut neoplasia in mice and protects against the production of reactive oxygen species. Cancer Research. 2010;70(22):9423-9433.
  • [27] Elmore S. Apoptosis: A review of programmed cell death. Toxicologic Pathology. 2007;3 (4):495-516.
  • [28] Caglayan C, Temel Y, Kandemir FM, Yildirim S, Kucukler S. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut Res. 2018;25(21):20968-20984.
  • [29] Kandemir FM, Kucukler S, Eldutar E, Caglayan C. Chrysin Protects Rat Kidney from Paracetamol-Induced Oxidative Stress, Inflammation, Apoptosis, and Autophagy : A Multi-Biomarker Approach. Sci. Pharm.2017;85(4):1-12.
  • [30] Chen J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harbor Perspectives in Medicine. 2016;6 (3):a026104.
  • [31] Kumar B, Iqbal MA, Singh RK, Bamezai RNK. Resveratrol inhibits TIGAR to promote ROS induced apoptosis and autophagy. Biochimie. 2015;118:26-35.
Year 2020, Volume: 9 Issue: 2, 35 - 41, 30.12.2020
https://doi.org/10.46810/tdfd.796339

Abstract

Project Number

BAP-FEF.2017.00.017

References

  • [1] Majumder R, Parida P, Paul S, Basak P. In vitro and in silico study of aloe vera leaf extract against human breast cancer. Natural Product Research. 2020;34(16):2363-2366.
  • [2] Bozorgi A, Khazaei M, Khazaei MR. New findings on breast cancer stem cells: A review. Journal of Breast Cancer. 2015;18(4):303-312.
  • [3] Kutluk T, Kars A. Kanser Konusunda Genel Bilgiler. T.C. Sağlık Bakanlığı Kanser ve Savaş Daire Başkanlığı Yayınları (http://sbv.saglik.gov.tr/Ekutuphaane/kitaplar/kanser.pdf). 1. Baskı: Ankara; 2001.
  • [4] Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: Mechanisms of Action and Clinical Strategies. Nature Reviews Cancer. 2003;3(5):330-338.
  • [5] Correia A, Silva D, Correia A, Vilanova M, Gärtner F, Vale N. Study of New Therapeutic Strategies to Combat Breast Cancer Using Drug Combinations. Biomolecules. 2018; 8(4):175.
  • [6] Li Z, Pan LL, Zhang FL, Wang Z, Shen YY, Zhang ZZ. Preparation and characterization of fullerene (C60) amino acid nanoparticles for liver cancer cell treatment. Journal of Nanoscience and Nanotechnology. 2014;14 (6):4513-4518.
  • [7] Harhaji L, Isakovic A, Raicevic N, Markovic Z, Todorovic-Markovic B, Nikolic N, et al. Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. European Journal of Pharmacology. 2007;568(1-3):89-98.
  • [8] Green DR, Chipuk JE. p53 and metabolism: Inside the TIGAR. Cell. 2006;126(1): 30-32.
  • [9] Bensaad K, Tsuruta A, Selak MA, Vidal MNC, Nakano K, Bartrons R, et al. TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis. Cell. 2006;126(1):107-120.
  • [10] Pfeffer CM, Singh ATK. Apoptosis: A Target for anticancer therapy. International Journal of Molecular Sciences. 2018;19(2): 448.
  • [11] Temel Y, Taysi MŞ. The Effect of Mercury Chloride and Boric Acid on Rat Erythrocyte Enzymes. Biol Trace Elem Res. 2018:177-182.
  • [12] Temel Y, Koçyigit UM, Taysi MS, et al. Purification of glutathione S-transferase enzyme from quail liver tissue and inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3 (aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives on the enzyme activity. J Biochem Mol Toxicol. 2018; 32(3):e22034.
  • [13] Aybek H, Temel Y, Ahmed BM, Ağca CA, Çiftci M. Deciphering of the effect of chemotherapeutic agents on human glutathione S-transferase enzyme and MCF-7 cell line. Protein Pept. Lett. 2020;27:1-7.
  • [14] Liou GY, Storz P. Reactive oxygen species in cancer. Free Radical Research. 2010;44 (5):479-496.
  • [15] Yip NC, Fombon IS, Liu P, Brown S, Kannappan V, Armesilla AL, et al. Disulfiram modulated ROS–MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties. British Journal of Cancer. 2011;104(10):1564-1574.
  • [16] Schilsky RL. Biochemical and Clinical Pharmacology of 5-Fluorouracil. Oncolgy. 1998;12(10):13-18.
  • [17] Cai J, Chen S, Zhang W, Wei Y, Lu J, Xing J, et al. Proteomic analysis of differentially expressed proteins in 5-fluorouracil-treated human breast cancer MCF-7 cells. Clinical and Translational Oncology. 2014;16 (7):650-659.
  • [18] Ge ZH, Wang ZX, Yu TL, Yang N, Sun Y, Hao CL, et al. Morphine improved the antitumor effects on Mcf-7 cells in combination with 5-fluorouracil. Biomedicine & Pharmacotherapy. 2014;68(3):299-305.
  • [19] Wang F, Jin C, Liang H, Tang Y, Zhang H, Yang Y. Effects of Fullerene C60 Nanoparticles on A549 Cells. Environmental Toxicology and Pharmacology. 2014;37(2):656-661.
  • [20] Lynchak OV, Prylutskyy YI, Rybalchenko VK, Kyzyma OA, Soloviov D, Kostjukov VV, et al. Comparative analysis of the antineoplastic activity of C60 fullerene with 5-fluorouracil and pyrrole derivative in vivo. Nanoscale Research Letters. 2017;12(1):1-6.
  • [21] Raza K, Thotakura N, Kumar P, Joshi M, Bhushan S, Bhatia A, et al. C60-Fullerenes for delivery of docetaxel to breast cancer cells: A promising approach for enhanced efficacy and better pharmacokinetic profile. International Journal of Pharmaceutics. 2015;495(1):551-559.
  • [22] Hecht F, Pessoa CF, Gentile LB, Rosenthal D, Carvalho DP, Fortunato RS. The role of oxidative stress on breast cancer development and therapy. Tumor Biology. 2016;37(4):4281-4291.
  • [23] Valko M, Rhodes C, Moncol J, Izakovic MM, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions. 2006;160(1):1-40.
  • [24] Focaccetti C, Bruno A, Magnani E, Bartolini D, Principi E, Dallaglio K, et al. Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PLoS One. 2015;10(2):e0115686.
  • [25] Suzuki S, Okada M, Shibuya K, Seino M, Sato A, Takeda H, et al. JNK suppression of chemotherapeutic agents-ınduced ROS confers chemoresistance on pancreatic cancer stem cells. Oncotarget. 2015;6(1):458-470.
  • [26] Darsigny M, Babeu JP, Seidman EG, Gendron FP, Levy E, Carrier J, et al. Hepatocyte nuclear factor-4α promotes gut neoplasia in mice and protects against the production of reactive oxygen species. Cancer Research. 2010;70(22):9423-9433.
  • [27] Elmore S. Apoptosis: A review of programmed cell death. Toxicologic Pathology. 2007;3 (4):495-516.
  • [28] Caglayan C, Temel Y, Kandemir FM, Yildirim S, Kucukler S. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut Res. 2018;25(21):20968-20984.
  • [29] Kandemir FM, Kucukler S, Eldutar E, Caglayan C. Chrysin Protects Rat Kidney from Paracetamol-Induced Oxidative Stress, Inflammation, Apoptosis, and Autophagy : A Multi-Biomarker Approach. Sci. Pharm.2017;85(4):1-12.
  • [30] Chen J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harbor Perspectives in Medicine. 2016;6 (3):a026104.
  • [31] Kumar B, Iqbal MA, Singh RK, Bamezai RNK. Resveratrol inhibits TIGAR to promote ROS induced apoptosis and autophagy. Biochimie. 2015;118:26-35.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Havva Aybek This is me 0000-0002-3831-4780

Can Ali Agca 0000-0002-0244-3767

Mehmet Çiftci 0000-0002-1748-3729

Project Number BAP-FEF.2017.00.017
Publication Date December 30, 2020
Published in Issue Year 2020 Volume: 9 Issue: 2

Cite

APA Aybek, H., Agca, C. A., & Çiftci, M. (2020). 5-Fluorourasil (5-FU) ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik ve Apoptotik Etkilerinin Araştırılması. Türk Doğa Ve Fen Dergisi, 9(2), 35-41. https://doi.org/10.46810/tdfd.796339
AMA Aybek H, Agca CA, Çiftci M. 5-Fluorourasil (5-FU) ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik ve Apoptotik Etkilerinin Araştırılması. TJNS. December 2020;9(2):35-41. doi:10.46810/tdfd.796339
Chicago Aybek, Havva, Can Ali Agca, and Mehmet Çiftci. “5-Fluorourasil (5-FU) Ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik Ve Apoptotik Etkilerinin Araştırılması”. Türk Doğa Ve Fen Dergisi 9, no. 2 (December 2020): 35-41. https://doi.org/10.46810/tdfd.796339.
EndNote Aybek H, Agca CA, Çiftci M (December 1, 2020) 5-Fluorourasil (5-FU) ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik ve Apoptotik Etkilerinin Araştırılması. Türk Doğa ve Fen Dergisi 9 2 35–41.
IEEE H. Aybek, C. A. Agca, and M. Çiftci, “5-Fluorourasil (5-FU) ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik ve Apoptotik Etkilerinin Araştırılması”, TJNS, vol. 9, no. 2, pp. 35–41, 2020, doi: 10.46810/tdfd.796339.
ISNAD Aybek, Havva et al. “5-Fluorourasil (5-FU) Ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik Ve Apoptotik Etkilerinin Araştırılması”. Türk Doğa ve Fen Dergisi 9/2 (December 2020), 35-41. https://doi.org/10.46810/tdfd.796339.
JAMA Aybek H, Agca CA, Çiftci M. 5-Fluorourasil (5-FU) ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik ve Apoptotik Etkilerinin Araştırılması. TJNS. 2020;9:35–41.
MLA Aybek, Havva et al. “5-Fluorourasil (5-FU) Ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik Ve Apoptotik Etkilerinin Araştırılması”. Türk Doğa Ve Fen Dergisi, vol. 9, no. 2, 2020, pp. 35-41, doi:10.46810/tdfd.796339.
Vancouver Aybek H, Agca CA, Çiftci M. 5-Fluorourasil (5-FU) ve C60 Nanopartikülünün Meme Kanseri (MCF-7) Hücre Hattı Üzerine Sitotoksik ve Apoptotik Etkilerinin Araştırılması. TJNS. 2020;9(2):35-41.

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