TR-Dizin İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/396
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Article Dalak Tirozin Kinaz ve Histon Deasetilaz Enzim İnhibisyonunun FLT3-ITD(+) Akut Miyeloid Lösemi Hücreleri Üzerindeki Anti-Lösemik Etkisi(2025) Akcok, E. Basak Gencer; Şansaçar, MerveSpleen Tyrosine Kinase (Syk) crosstalk with paramount signaling pathways which has a major contribution in the progress of acute myeloid leukemia (AML) such as PI3K, NFκB and JAK/STAT signaling pathways. Several studies recorded that deregulated Histone Deacetylase (HDAC) enzymes are involved in the pathogenesis of AML. The study aims to reveal the effect of Syk and HDAC co-inhibition on MOLM-13 and MV4-11 AML cells which are harboring the receptor of FMS-like Tyrosine Kinase's (FLT3) Internal Tandem Duplication (ITD). AML cells were incubated using both R406 and HDAC inhibitors alone and in combination, and increasing concentrations of R406 and HDAC inhibitors revealed a significant reduction of MOLM-13 and MV4-11 cells’ viability using MTT cell viability test. Furthermore, the combination of R406 and VPA resulted in a reduction in the proliferation of both cells correlated with the synergistic effect of the two drugs revealed by the combination index (CI). Moreover, investigating apoptosis for the combined administration of drugs resulted in induced apoptosis in AML cells using Annexin-V/PI double staining. We observed also changes in the mRNA expression level of MYC after combination treatment via Real-time PCR analysis. Even though further studies are needed, targeting Syk and HDAC enzymes in AML cells may be a good strategy in the treatment of patients suffering from AML with FLT3 ITD (+) mutation.Article The Therapeutic Potential of Targeting Hdac6 With Tubastatin a in Tfk-1 and Egi-1 Cholangiocarcinoma Cells(2021) Yenigül, Münevver; Akcok, E. Basak GencerCholangiocarcinoma (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.