Browsing by Author "Yenigül, Münevver"

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Histon Deasetilaz İnhibisyonu ve Otofaji Modülasyonunun Kolanjiokarsinoma Hücrelerine Etkisi
(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2022) Yenigül, Münevver; Yenigül, Münevver; Akçok, Emel Başak Gencer; Akçok, İsmail
Cholangiocarcinoma (CCA), also known as biliary tract cancer, is a heterogeneous group of malignancies formed by the differentiation of epithelial cells in the biliary tract. CCA is the second most common primary liver tumor and it has both an increasing rate and high mortality worldwide with its late diagnosis, refractory type, and aggressiveness. The effects of autophagy modulators and HDAC inhibitors in CCA are not fully known. This study is proposed a novel treatment approach with the combinational therapy of autophagy and HDAC inhibitors for CCA patients. In results obtained with alone HDACis, alone autophagy modulators, and combinations of HDACis and autophagy modulators, Nocodazole from autophagy modulators and MS-275 and Romidepsin from HDAC inhibitors showed a better synergistic effect on the TFK-1 and EGI-1 cell lines of the cholangiocarcinoma. In cell cycle analysis of the combination, was achieved arrest at the S phase and G2/M phase. In conclusion, this study highlights the important combination of HDAC inhibitors and autophagy modulators, which is a promising therapy in CCA. Keywords: Cholangiocarcinoma, HDAC inhibitors, Autophagy modulators, Combination therapy
The Therapeutic Potential of Targeting Hdac6 With Tubastatin a in Tfk-1 and Egi-1 Cholangiocarcinoma Cells
(2021) Yenigül, Münevver; Akcok, E. Basak Gencer
Cholangiocarcinoma (CCA) is a highly aggressive and invasive malignancy with a poor diagnosis because of the resistance, relapse and limited therapy. Histone deacetylases (HDAC) are a class of enzyme that have important roles in epigenetic modulations. These enzymes are intensely studied and HDAC inhibitors are considered as potent anticancer agents in both solid tumors and hematological malignancies. HDAC inhibitors can affect and induce different mechanisms such as cell cycle arrest, differentiation, and cell death. In this study, we aim to investigate the cytotoxic effect of Tubastatin A, which is a selective HDAC6 inhibitor, on cholangiocarcinoma cell lines, TFK-1 and EGI-1, by MTT assay. Besides, it was aimed to examine the impact on colony formation potential of the cells. The effect of the inhibitor on cell cycle distribution was also examined by using flow cytometry. Tubastatin A has significantly decreased the colony formation and changed cell cycle progression. Taken together, our results suggest that Tubastatin A could be a potent inhibitor against cholangiocarcinoma. On the basis of these results, further mechanistic studies are required to elucidate the antineoplastic activity of Tubastatin A.