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    Anticancer activity, hTERT expression and telomere length analysis in SH-SY5Y neuroblastoma cell lines applied to docetaxel
    (Elsevier, 05.02.2023) Inandiklioglu, Nihal; Tas, Ayca; Agbektas, Tugba; Tuncbilek, Zuhal; Raheem, Kayode Yomi; Cinar, Gulcihan; Silig, Yavuz
    Neuroblastoma is the most common extracranial solid tumor of infancy in a broad range of clinical courses, ranging from spontaneous regression to fatal progression. Telomere maintenance plays an impor- tant role in genome stability and cell proliferation. Telomerase reverse transcriptase (hTERT in humans) is a catalytic subunit of the enzyme telomerase. In this study, it was aimed to determine the anticancer ac- tivity of the docetaxel chemotherapeutic agent in neuroblastoma cell line (SH-SY5Y) and to investigate its effect on hTERT gene expression level and telomere length. Molecular docking studies were performed on docetaxel with the crystal structure of telomerase. The electronic properties of docetaxel were calculated using the density functional theory (DFT) method. SH-SY5Y cells were treated for 24, 48 and 72 h with specific concentrations of docetaxel drug ranging from 1 to 100 μg/ml. IC50 doses of docetaxel were de- termined and administered to SH-SY5Y cells, followed by RNA isolation. hTERT and MYC gene expression levels and telomere length were measured in the docetaxel-treated sample using the RT-PCR method. In addition, theoretical analyzes were made. The IC50 values of docetaxel after 24, 48 and 72 h were 8.32 ±1.45 μg/ml, 7.67 ±2.56 μg/ml and 5.51 ±1.24 μg/ml, respectively. According to the results obtained, docetaxel was found to have the highest activity in 72 h of incubation. It was determined that the do- cetaxel drug decreased the expression level of the hTERT gene in SH-SY5Y cells. Telomere lengths were significantly reduced in the docetaxel treated SH-SY5Y cell line compared to the control group ( p < 0.05). Molecular docking analysis results were in agreement with the experiments. Analysis results indicated a good interaction between docetaxel and the active site of telomerase. The results of this study, reinforced by molecular docking analyzes, might be proved valuable for the development of potent telomerase in- hibitors.
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    Anticancer activity, hTERT expression and telomere length analysis in SH-SY5Y neuroblastoma cell lines applied to docetaxel
    (Elsevier B.V., 2023) Inandiklioglu, Nihal; Tas, Ayca; Agbektas, Tugba; Tuncbilek, Zuhal; Raheem, Kayode Yomi; Cinar, Gulcihan; Silig, Yavuz
    Neuroblastoma is the most common extracranial solid tumor of infancy in a broad range of clinical courses, ranging from spontaneous regression to fatal progression. Telomere maintenance plays an important role in genome stability and cell proliferation. Telomerase reverse transcriptase (hTERT in humans) is a catalytic subunit of the enzyme telomerase. In this study, it was aimed to determine the anticancer activity of the docetaxel chemotherapeutic agent in neuroblastoma cell line (SH-SY5Y) and to investigate its effect on hTERT gene expression level and telomere length. Molecular docking studies were performed on docetaxel with the crystal structure of telomerase. The electronic properties of docetaxel were calculated using the density functional theory (DFT) method. SH-SY5Y cells were treated for 24, 48 and 72 h with specific concentrations of docetaxel drug ranging from 1 to 100 µg/ml. IC50 doses of docetaxel were determined and administered to SH-SY5Y cells, followed by RNA isolation. hTERT and MYC gene expression levels and telomere length were measured in the docetaxel-treated sample using the RT-PCR method. In addition, theoretical analyzes were made. The IC50 values of docetaxel after 24, 48 and 72 h were 8.32±1.45 μg/ml, 7.67±2.56 μg/ml and 5.51±1.24 μg/ml, respectively. According to the results obtained, docetaxel was found to have the highest activity in 72 h of incubation. It was determined that the docetaxel drug decreased the expression level of the hTERT gene in SH-SY5Y cells. Telomere lengths were significantly reduced in the docetaxel treated SH-SY5Y cell line compared to the control group (p < 0.05). Molecular docking analysis results were in agreement with the experiments. Analysis results indicated a good interaction between docetaxel and the active site of telomerase. The results of this study, reinforced by molecular docking analyzes, might be proved valuable for the development of potent telomerase inhibitors. © 2022
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    Effect of azomethine group containing compounds on gene profiles in Wnt and MAPK signal patterns in lung cancer cell line: In silico and in vitro analyses
    (Elsevier, 2023/3/5) Agbektas, Tugba; Zontul, Cemile; Ozturk, Alpaslan; Huseynzada, Alakbar; Ganbarova, Rana; Hasanova, Ulviyya; Cinar, Gulcihan; Tas, Ayca; Kaya, Savas; Chtita, Samir; Silig, Yavuz
    The main aims of anticancer drug development studies is to reduce the toxicity of the developed com- pound and maximize the effectiveness, as well as the discovery of artificial and natural compounds. In recent years, scientists have accelerated their research on new molecules with anticancer activity. In re- cent years, new drugs containing the azomethine group are thought to be promising in the treatment of cancer. In this study, firstly, the synthesis of azomethine group-containing compounds, i.e. Schiff bases, which was designed theoretically, was carried out. Secondly, the application of the newly synthesized compounds 1, 2, 3 and 4 to the lung cancer cell line (A-549), followed by the determination of their anticancer activities, and finally the Wnt signaling pathway ( CSNK1A1, CTNNB1 ), MAPK signaling path- way ( DUSP1, DUSP2, DUSP4 and DUSP10 ) genes on expression levels was investigated. The compounds synthesized in our study were characterized by 1H and 13C NMR spectroscopy methods. The anticancer activities of the new synthesized molecules were determined in the A-549 lung cancer cell line using the MTT method. Expression levels of Wnt signaling pathway ( CSNK1A1, CTNNB1 ) and MAPK signaling path- way ( DUSP1, DUSP2, DUSP4 and DUSP10 ) genes were determined by RT-PCR method. In addition, A-549 cells were evaluated in terms of biochemical parameters. In addition to experimental studies, theoretical studies were carried out. Molecular docking results were found to be compatible with the experiments. Compounds 1, 2, 3 and 4 applied to cell line A-549 showed the highest activity after 72 h of incubation. As a result, it was determined that compounds 2 and 4 increased the expression of CTNNB1 and DUSP10 genes compared to the control group. It was determined that compound 4 increased the expression level of CSNK1A1, CTNNB1, DUSP1, DUSP2, DUSP4 and DUSP10 genes compared to other groups. A-549 lung can- cer cells showed a 70% reduction in GST levels in compound 1, while a 96% reduction in CAT levels in compound 1 compared to the control group. Molecular docking calculations supported the Experimental observations. Calculated binding energies provided important clues about drug efficiencies of molecules studied.
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    Experimental and theoretical insights about the effect of some newly designed azomethine group?contained macroheterocycles on oxidative stress and DNA repair gene profiles in neuroblastoma cell lines
    (Elsevier, 2023/8/5) Cinar, Gulcihan; Agbektas, Tugba; Huseynzada, Alakbar; Aliyeva, Gunel; Aghayev, Mirjavid; Hasanova, Ulviyya; Kaya, Savas; Chtita, Samir; Nour, Hassan; Tas, Ayca; Silig, Yavuz
    We report herein the synthesis of new azomethine group containing forty-, sixty-eight- and seventy- two-membered macroheterocyclic compounds and the investigation of their activity against the neurob- lastoma cell line. The synthesis of targeted compounds was done by condensation of dialdehydes with polyamines and their structures were investigated by 1 H and 13 C NMR and MALDI MS methods. Anti- cancer activity of these newly synthesized molecules was studied in the neuroblastoma (SH-SY5Y) cell line at eight different concentrations (1–100 μg/ml) for 24 h, 48 hrs and 72 h by MTT method. In ad- dition to it, oxidative stress (GPX1, PRDX1, CAT, SOD1, NQO1) and DNA repair (ATR, ERCC1, CDKN1A, PRKDC) gene profiles were also investigated by RT-PCR method. It was found that all synthesized compounds showed the highest activity after 72 h of incubation. PRDX1 gene expression in the case of all investi- gated compounds was found to be higher than the control group, whereas ABCB1 (MDR) gene expression increased only in the case of molecule 1. Results also demonstrate that the expression levels of GPX and SOD1 genes were high in the case of molecule 2, whereas molecule 1 manifested low expression levels of ERCC1, ATR, CDKN1A, PRKDC, GPX1, ABCB1(MDR), CAT, SOD1 and NQO1 genes. Along with experimen- tal studies, theoretical studies were also carried out. The String v11 program was used to determine the interaction of proteins involved in oxidative stress and DNA repair mechanisms with other proteins. The results of the molecular docking analysis were found to be in good agreement with the experiments.