Yeni Sentezlenen Antitirozinaz Aktiviteye Sahip Kojik Asit Türevlerinin A375 Malin Melanoma Hücre Hattında Sitotoksisite ve Hücre Ölümü Üzerine Etkisinin Aydınlatılması
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Tarih
2021Yazar
Felekoğlu, Rıdvan
Ambargo Süresi
Acik erisimÜst veri
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Felekoglu, R., The Effect of Kojic Acid Derivatives with New Synthesized
Antithyrosinase Activity on Cytotoxicity and Cell Death in the A375 Malign
Melanoma Cell Line, Hacettepe University Graduate School of Health Sciences
Biochemistry Department of Master Thesis, Ankara 2021. In this thesis study, kojic
acid derivative compounds which are tyrosinase inhibitors were investigated. The
mechanisms that lead to death and molecular death pathways in the cells caused by which
compound with the strongest cytotoxic properties against A375 human malignant
melanoma cells have been examined. As a result of the SRB test conducted for
cytotoxicity, it was observed that Compound-15, whose IC50 value was measured as 9.81
µM, effectively killed living cells. The enzymatic inhibition of Compound-15 was
determined spectrophotometrically using the cytosol of B16F10 mice cells and kojic acid
as a control. According to spectrophotometry results, it was demonstrated that Compound 15 could compete with kojic acid. Furthermore, the IC50 values of kojic acid and
Compound-15 were obtained as 59.20 µM and 76.79 µM respectively. The apoptosis test
was carried out and as stated in test results, Compound-15 took the cells to the last stage
of apoptosis. Then, to determine which apoptotic genes in A375 cells affected by
Compound-15, RNA was purified from cells, and cDNA was synthesized. Apoptotic p53
and Bax, anti-apoptotic Bcl-2 as well as Jnk, Mdm2 and Mdr1 gene levels were examined.
Bcl-2 levels decreased 0.5 times and Bax levels increased 2.4 times compared to control.
Thus, it has been observed that Compound-15 leads cells to apoptosis in 24 hours. The
ratio of Mdm2 in which p53 showed early activity, increased 3 times compared to p53,
supports the idea that increased p53 level in cells may have been taken under control. The
results obtained in the first 24 hours for the Mdr-1 gene were high. No significant change
was observed in the Jnk gene compared to the control. The death pathway triggered by
Compound-15 in melanoma cells was determined by flow cytometry and according to the
results, it can be said that the late apoptosis rate of 58.8% leads A375 cells to more
effective programmed death. As a result of the western blot and β-Actin, p53 and Mdr1
protein analysis performed on A375 cells, it was concluded that the findings were
consistent with the gene expression results.
Key words : Kojic acid, p53, apoptosis, gene expression, cytotoxicity
Bağlantı
http://hdl.handle.net/11655/23654Koleksiyonlar
Künye
MLA : Felekoğlu, Rıdvan ''Yeni Sentezlenen Antitirozinaz Aktiviteye Sahip Kojik Asit Türevlerinin A375 Malin Melanoma Hücre Hattında Sitotoksisite ve Hücre Ölümü Üzerine Etkisinin Aydınlatılması.'' (2021). APA : Felekoğlu, R. (2021). Yeni Sentezlenen Antitirozinaz Aktiviteye Sahip Kojik Asit Türevlerinin A375 Malin Melanoma Hücre Hattında Sitotoksisite ve Hücre Ölümü Üzerine Etkisinin Aydınlatılması. ISO 690 : FELEKOĞLU, Rıdvan. Yeni Sentezlenen Antitirozinaz Aktiviteye Sahip Kojik Asit Türevlerinin A375 Malin Melanoma Hücre Hattında Sitotoksisite ve Hücre Ölümü Üzerine Etkisinin Aydınlatılması. 2021.Aşağıdaki lisans dosyası bu öğe ile ilişkilidir: