Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Comparison of Rapamycin and 3-Methyladenine in Cisplatin-Induced Experimental Cardiotoxicity(Wiley, 2026) Kaymak, Emin; Karabulut, Derya; Yalcin, Betul; Guner, Serife Ayaz; Ozturk, Emel; Findik, Fatma; Boyvat, DuduIn this study, we evaluated how cisplatin cardiotoxicity affects the histological and endocrine functions of the heart and autophagy while using Rapamycin(Rapa) and 3-methyladenine(3-MA) as autophagy activators and inhibitors. Control, Cisplatin (Cis), 3-methyladenine + Cisplatin (3-MA + Cis) and Rapamycin + Cisplatin (Rapa + Cis). Rapa and 3-MA were administered for 15 days, while a single dose of cisplatin was administered on the 7th day. Natriuretic peptide receptor-A(NPR-A), receptor-B(NPR-B) and biochemically atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) levels were evaluated in heart tissue. Cis caused a statistically significant increase in NPR-A and NPR-B expression, as well as ANP and BNP levels. However, the levels of Beclin-1 and LC3B were not statistically significant. Rapa was more effective than 3-MA + Cis on NPR-A and NPR-B expressions, but did not show the same effect on ANP and NT-proBNP levels. Cis caused an increase in Beclin-1 and LC3B levels, while a decrease was observed in both 3-MA + Cis and Rapa + Cis groups. Our results revealed that Cis cardiotoxicity disrupts autophagy and endocrine function of the heart. It was concluded that by continuing the activator and inhibitor substances after Cis application, more effective results can be obtained in Beclin-1 expression than LC3B expression and that they can be effective in eliminating the toxicity of Cis.Article Citation - WoS: 3Citation - Scopus: 4Rapamycin and Niacin Combination Induces Apoptosis and Cell Cycle Arrest Through Autophagy Activation on Acute Myeloid Leukemia Cells(Springer, 2024-12-23) Subay, Lale Beril; Akcok, Emel Basak Gencer; Akcok, Ismail; Gencer Akçok, Emel BaşakBackgroundAcute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by disorders in stem cell differentiation and excessive proliferation resulting in clonal expansion of dysfunctional cells called myeloid blasts. The combination of chemotherapeutic agents with natural product-based molecules is promising in the treatment of AML. In this study, we aim to investigate the anti-cancer effect of Rapamycin and Niacin combination on THP-1 and NB4 AML cell lines.Methods and ResultsThe anti-proliferative effects of Rapamycin and Niacin were determined by MTT cell viability assay in a dose- and time-dependent manner. The combination indexes were calculated by isobologram analysis. Furthermore, apoptosis was investigated by Annexin-V/Propidium Iodide(PI) double staining and cell cycle distribution was measured by PI staining. The expression levels of autophagy-related proteins were detected by western blotting. The combination of Rapamycin and Niacin synergistically decreased cell viability of AML cell lines. The combination treatment induced the apoptotic cell population of THP-1 and NB4 by 4.9-fold and 7.3-fold, respectively. In THP-1 cells, the cell cycle was arrested at the G2/M phase by 10% whereas the NB4 cells were accumulated at the G0/G1 phase. The combination treatment decreased Akt and p-Akt expression. Besides, the ATG7 expression was reduced by combination treatment on THP-1 cells. Similarly, the ATG5 level was downregulated in NB4 cells. The level of LC3B-II/LC3B-I, which is an indicator of autophagy flux, was upregulated in THP-1 and NB4 cells.ConclusionAlthough further studies are required, the combination of Rapamycin and Niacin combats cell proliferation by inducing cellular apoptosis, cell cycle arrest and autophagy activation.Article Efficacy of Combinatorial Inhibition of Hedgehog and Autophagy Pathways on the Survival of AML Cell Lines(Academic Press inc Elsevier Science, 2025-08) Sansacar, Merve; Pepe, Nihan Aktas; Akcok, Emel Basak Gencer; El Khatib, Mona; Gencer Akçok, Emel BaşakAcute myeloid leukemia (AML) is a common hematopoietic disease that results from diverse genetic abnormalities. Dysregulation of important signaling pathways, including the PI3K/AKT/mTOR, Wnt and Hedgehog pathways, plays crucial roles in the development of AML. Hedgehog pathway (Hh) is a conserved signaling pathway that is crucial throughout embryogenesis. Hh plays an important role in the regulation of autophagy, known as the cellular recycling process of organelles and unwanted proteins. Many studies have noted that the modulation of autophagy could act as a survival mechanism in AML. Considering the pivotal role of autophagy and Hh signaling in AML, understanding the relationship between these pathways is important for overcoming leukemia. Therefore, we examined the efficacy of Hh inhibition by GLI-ANTagonist 61 (GANT61) in MOLM-13 and CMK cells via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenil-2H-tetrazolium bromide (MTT) cell viability assays. GANT61 resulted in decreased cell viability in both cell lines. Therefore, we focused on the outcome of autophagy modulation in AML cells. We observed that the autophagy inhibitors ammonium chloride (NH4CI), chloroquine (CQ), and nocodazole led to a significant reduction in the proliferation of both cell lines. Cotreatment with autophagy pathway inhibitors and GANT61 synergistically affected both AML cell lines. Moreover, dual targeting of these pathways resulted in arrest at the G0/G1 phase in MOLM-13 cells but not in CMK cells. Furthermore, the combination of nocodazole and GANT61 increased the expression level of LC3B-II in both cell lines. Compared with that in the untreated control cells, the GLI1 gene expression level in both cell lines was significantly lower after GANT61 and autophagy cotreatment. In conclusion, targeting Hh and autophagy could be a favorable option to combat AML.