Yazar "Akgün, Oğuzhan" seçeneğine göre listele

Listeleniyor 1 - 3 / 3
  • Küçük Resim
    Öğe
    Effective and new potent drug combination: histone deacetylase and Wnt/beta-catenin pathway inhibitors in lung carcinoma cells
    (Wiley, 2019) Akgün, Oğuzhan; Erkısa Genel, Merve; Arı, Ferda
    Lung cancer is the most commonly diagnosed cancer worldwide with a high mortality rate. In this study, the therapeutic effect of combination valproic acid and niclosamide was investigated on human lung cancer cell line. The effects of the compounds alone and combination therapy on cell viability were determined by sulforhodamine B and adenosine 5 '-triphosphate viability assays. Flow cytometry was used to determine the cell death mechanism and DNA damage levels responsible for the cytotoxic effects of combination therapy. The presence of apoptosis in cells was supported by fluorescence microscopy and also by using inhibitors of the apoptotic signaling pathway. The increase in cellular reactive oxygen species (ROS) level in combination therapy was determined by H2DCFDA staining. The effect of N-acetyl-l-cysteine combination on ROS increase was investigated on cell viability. In addition, the expression levels of the proteins associated with epigenetic regulation and cell death were analyzed by Western blotting and gene expression levels were determined using real-time quantitative polymerase chain reaction.It was observed that the combination therapy showed a cytotoxic effect on the A549 lung cancer cells compared to the individual use of the inhibitors. The absence of this effect on normal lung cells revealed the presence of a selective toxic effect. When the mechanism of cytotoxicity is examined, it has been observed that combination therapy initiates the activation of tumor necrosis receptors and causes apoptosis by activated caspase. It was also observed that this extrinsic apoptotic pathway was activated on the mitochondrial pathway. In addition, ER stress and mitochondrial membrane potential loss associated with increased ROS levels induce cell death. When the data in this study were evaluated, combination therapy caused a dramatic decrease in cell viability by inducing the extrinsic apoptotic pathway in lung cancer cell line. Therefore, it was concluded that it can be used as an effective and new treatment option for lung cancer.
  • Küçük Resim
    Öğe
    Epigenetic modulators combination with chemotherapy in breast cancer cells
    (Wiley, 2021) Arı, Ferda; Napieralski, Rudolf; Akgün, Oğuzhan; Magdolen, Viktor; Ulukaya, Engin
    Despite the concerning adverse effects on tumour development, epigenetic drugsare very promising in cancer treatment. The aim of this study was to compare the dif-ferential effects of standard chemotherapy regimens (FEC: 5-fluorouracil plus epi-rubicine plus cyclophosphamide) in combination with epigenetic modulators(decitabine, valproic acid): (a) on gene methylation levels of selected tumour bio-markers (LINE-1, uPA, PAI-1, DAPK); (b) their expression status (uPA and PAI-1);(c) differentiation status (5meC and H3K27me3). Furthermore, cell survival as well aschanges concerning the invasion capacity were monitored in cell culture models ofbreast cancer (MCF-7, MDA-MB-231). A significant overall decrease of cell survivalwas observed in the FEC-containing combination therapies for both cell lines. Meth-ylation results showed a general tendency towards increased demethylation of theuPA and PAI-1 gene promoters for the MCF-7 cells, as well as the proapoptoticDAPK gene in the treatment regimens for both cell lines. The uPA and PAI-1 antigenlevels were mainly increased in the supernatant of FEC-only treated MDA-MB-231cells. DAC-only treatment induced an increase of secreted uPA protein in MCF-7 cellculture, while most of the VPA-containing regimens also induced uPA and PAI-1expression in MCF-7 cell fractions. Epigenetically active substances can also induce are-differentiation in tumour cells, as shown by 5meC, H3K27me3 applying ICC.Significance of the study: Epigenetic modulators especially in the highlyundifferentiated and highly malignant MDA-MB-231 tumour cells significantlyreduced tumour malignancy thus; further clinical studies applying specific combina-tion therapies with epigenetic modulators may be warranted.
  • Küçük Resim
    Öğe
    Quantification of DNA damage products by gas chromatography tandem mass spectrometry in lung cell lines and prevention effect of thyme antioxidants on oxidative induced DNA damage
    (Elsevier Science Bv, 2018) Aybastıer, Önder; Dawbaa, Sam; Demir, Cevdet; Akgün, Oğuzhan; Ulukaya, Engin; Arı, Ferda
    Lung cancer has a high treatment cost and poor prognosis in comparison to other types of cancers. This work was involved in studying oxidative DNA base damage inhibition. Accordingly, standard carvacrol, thymol, thymoquinone with water and water-methanol extract of thyme (Origanum vulgare L. subsp. hirtum (link.) Ietswaart), thyme oil and thyme water were prepared and investigated for their efficacy to inhibit DNA oxidative damage formed by H2O2 in malignant lung cells (A549). The antioxidant capacity by ABTS assay was 271.73 +/- 11.45 mg trolox equivalent/mL for thyme oil. HPLC analysis was carried out to determine the contents of different thyme extracts, results showing the presence of carvacrol, thymol, protocatechuic acid, caffeic acid, epicatechin and rosmarinic acid in water and water-methanol extracts while only carvacrol and thymol were found in thyme oil and thyme water. After DNA isolation from the cultured cells, the formed oxidative induced DNA damage products were analysed using GC-MS/MS. It was proven that the antioxidants in the cell culture media have succeeded to inhibit oxidative DNA base damage. Thymoquinone was shown to be the best protectant antioxidant among other antioxidants against the formation of oxidative DNA damage, whereas water-methanol extract of thyme was the best among the plant-sourced samples. Thymoquinone and thyme water-methanol extract were investigated for their efficacy on cultured healthy lung cells (BEAS-2B), and it was proven that they are efficient in protection against the oxidation of DNA of healthy lung cells too.