Browsing by Author "Yenigül, Münevver"

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The effect of histone deacetylase inhibition and autophagy modulation on the cholangiocarcinoma cells
(Abdullah Gül Üniversitesi, Fen Bilimleri Enstitüsü, 2022) Yenigül, Münevver; AGÜ, Fen Bilimleri Enstitüsü, Biyomühendislik Ana Bilim Dalı
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.
The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells
(SİVAS CUMHURİYET ÜNİVERSİTESİ: Sivas Cumhuriyet University, 2021) Yenigül, Münevver; Gencer Akçok, Emel Başak; 0000-0003-0468-721X; 0000-0002-6559-9144; AGÜ, Fen Bilimleri Enstitüsü, Biyomühendislik Ana Bilim Dalı; Yenigül, Münevver; Gencer Akçok, Emel Başak
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.
Tomatidine, a Steroidal Alkaloid, Synergizes with Cisplatin to Inhibit Cell Viability and Induce Cell Death Selectively on FLT3-ITD+ Acute Myeloid Leukemia Cells
(SPRINGER NATURE Link, 2024) Ayvaz, Havva Berre; Yenigül, Münevver; Gencer Akçok, Emel Başak; 0000-0002-5873-7879; 0000-0003-0468-721X; 0000-0002-6559-9144; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Ayvaz, Havva Berre; Yenigül, Münevver; Gencer Akçok, Emel Başak
Background: Acute Myeloid Leukemia (AML) is a hematological cancer that frequently presents with a range of side effects and drug resistance during anticancer drug treatment. The current study aims to achieve increased efficacy by combining lower doses of cisplatin with increasing concentrations of tomatidine in AML cells to increase efficacy. Methods: Anti-proliferative effects of single and combination of cisplatin and tomatidine were assessed via MTT cell viability assay. The Annexin V/Propidium Iodide Double Staining method was used to measure the apoptotic effects of combined tomatidine and cisplatin treatment. Then, Western Blot analysis was performed to measure Poly (ADP-ribose) polymerase (PARP) and Caspase-3 protein expression levels. Results: Cisplatin treatment with lower concentrations displayed high cytotoxic effects on AML cells, compared with tomatidine. The combination of the Inhibitory Concentration (IC) 20 value of cisplatin and increasing doses of tomatidine exhibited a significant decrease in cell viability relative to single treatments. The combination index analysis revealed a mild synergistic effect of cisplatin IC20 and varying tomatidine doses. The apoptosis induced when cisplatin was combined with 500 µM tomatidine by almost 20%, while the percentage of apoptosis in combination with 1 mM tomatidine was measured by 50% for both cell lines. The upregulation of proapoptotic cleaved-PARP (3.2 and 1.08-fold for THP-1 and MOLM-13, respectively) and downregulation in Caspase-3 (0.23 and 0.13-fold for THP-1 and MOLM-13, respectively) was detected. Conclusions: Together, the study indicated that when tomatidine combined with cisplatin on AML cell lines, a combinatorial anti-proliferative and apoptotic effect is observed. The combination of cisplatin with tomatidine may be a promising approach.