PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Citation - WoS: 6Citation - Scopus: 8Histone Deacetylase Inhibition and Autophagy Modulation Induces a Synergistic Antiproliferative Effect and Cell Death in Cholangiocarcinoma Cells(Amer Chemical Soc, 2023-06-08) Yenigul, Munevver; Akcok, Emel Basak Gencer; Gencer Akçok, Emel BaşakCholangiocarcinoma, also known as biliary tract cancer,is an aggressiveadenocarcinoma arising from epithelial cells lining the intra- andextrahepatic biliary system. The effects of autophagy modulators andhistone deacetylase (HDAC) inhibitors in cholangiocarcinoma are notfully known. It is essential to understand the molecular mechanismsand the effects of HDAC inhibitors in the context of cholangiocarcinoma.The antiproliferative effect of different HDAC inhibitors and autophagymodulation was investigated by the MTT cell viability assay in TFK-1and EGI-1 cholangiocarcinoma cell lines. Combination indexes werecalculated using CompuSyn software. Consequently, apoptosis was detectedby Annexin V/PI staining. The effect of the drugs on the cell cyclewas measured by the propidium iodide staining. The HDAC inhibitionwas confirmed via acetylated histone protein levels by western blotting.HDAC inhibitors, MS-275 and romidepsin, showed a better synergisticeffect with the nocodazole combination. The combination treatmentexerted its growth inhibitory effect by cell cycle arrest and inductionof apoptosis. The cell cycle analysis of the combination treatmentshowed that the S phase and G2/M phase were achieved. Moreover, thenecrotic and apoptotic cell population increased after single HDACinhibitors and combination treatment. The anti-cancer effect of HDACinhibitors is revealed by acetylation levels of histones. While acetylationlevels were increased in response to HDAC inhibitors and autophagymodulator combinations, the HDAC expression decreased. This studyhighlights the importance of the combination of HDAC inhibition andautophagy modulators and demonstrates a synergistic effect, whichcould be a promising therapy and novel treatment approach for cholangiocarcinoma.Article Citation - WoS: 3Citation - Scopus: 3Determination of Promising Inhibitors for N-SH2 Domain of SHP2 Tyrosine Phosphatase: An in Silico Study(Springer, 2024-05-13) Akcok, Emel Basak Gencer; Guner, Huseyin; Akcok, Ismail; Gencer Akçok, Emel BaşakThere are many genes that produce proteins related to diseases and these proteins can be targeted with drugs as a potential therapeutic approach. Recent advancement in drug discovery techniques have created new opportunities for treating variety of diseases by targeting disease-related proteins. Structure-based drug discovery is a faster and more cost-effective approach than traditional methods. SHP2 phosphatase, encoded by the PTPN11 gene, has been the focus of much attention due to its involvement in many types of diseases. The biological function of SHP2 is enabled mostly by protein-protein interaction through its SH2 domains. In this study, we report the identification of a potential small molecule inhibitor for the N-SH2 domain of SHP2 by structure-based drug discovery approach. We utilized molecular docking studies, followed by molecular dynamics simulations and MM/PBSA calculations, to analyze compounds retrieved from the Broad's Drug Repurposing Hub and ZINC15 databases. We selected 10 hit compounds with the best docking scores from the libraries and examined their binding properties in the N-SH2 domain. We found that compound CID 60838 (Irinotecan) was the most suitable compound with a binding free energy value of - 64.45 kcal/mol and significant interactions with the target residues in the domain.