Yazar "Karabay, Arzu Zeynep" seçeneğine göre listele

Listeleniyor 1 - 6 / 6
  • Küçük Resim
    Öğe
    An investigation on the effects of SIRT5 modulators on SIRT5 and cytochrome C protein expressions in K562 chronic myeloid leukemia cell line
    (University of Ankara, 2022) Özkan, Tülin; Koç, Aslı; Karabay, Arzu Zeynep; Hekmatshoar, Yalda; Sunguroğlu, Asuman
    Objective: SIRT5 is a mitochondrial protein that removes acetyl, malonyl and succinyl groups from lysine moieties in target proteins and interacts with cytochrome c and causes its deacetylation. There is no study on the effects of SIRT5 in K562 chronic myeloid leukemia cells. Resveratrol and Suramin are known to play a role in modulating the deacetylase and desuccinylase activities of SIRT5. It has been reported that Resveratrol induces apoptosis of K562 cells but effects of Suramin on the apoptosis of K562 cells are largely unknown. In this study, it was aimed to elucidate the effects of SIRT5 modulators Resveratrol and Suramin on proliferation and apoptosis of K562 cells and on SIRT5 and cytochrome c protein, a known target of SIRT5. Material and Method: K562 chronic myeloid leukemia cells were treated with increasing concentrations of suramin and resveratrol, cell proliferation was determined by MTT assay and BrdU incorporation. Apoptosis was determined with Annexin V staining by Flow cytometry. Western Blot analysis was performed to determine the effect of resveratrol and suramin on SIRT5 and Cytochrome c protein expression levels. Result and Discussion: Our results showed that suramin did not affect SIRT5 and cytochrome c protein expressions significantly and resveratrol decreased SIRT5 and increased cytochrome c expression. Suramin did not cause any changes on the apoptosis of K562 cells. Resveratrol decreased cell proliferation and induced apoptosis of K562 cells in accordance with the literature. The SIRT5-lowering effect of Resveratrol may have mediated its apoptotic effects.
  • Küçük Resim
    Öğe
    Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia
    (2024) Karabay, Arzu Zeynep; Özkan, Tülin; Gürel, Aynur Karadağ; Koç, Aslı; Hekmatshoar, Yalda; Sunguroğlu, Asuman; Aktan, Fügen; Büyükbingöl, Zeliha
    Chemotherapy resistance is a major obstacle in cancer therapy, and identifying novel druggable targets to reverse this phenomenon is essential. The exosome-mediated transmittance of drug resistance has been shown in various cancer models including ovarian and prostate cancer models. In this study, we aimed to investigate the role of exosomal miRNA transfer in chronic myeloid leukemia drug resistance. For this purpose, firstly exosomes were isolated from imatinib sensitive (K562S) and resistant (K562R) chronic myeloid leukemia (CML) cells and named as Sexo and Rexo, respectively. Then, miRNA microarray was used to compare miRNA profiles of K562S, K562R, Sexo, Rexo, and Rexo-treated K562S cells. According to our results, miR-125b-5p and miR-99a-5p exhibited increased expression in resistant cells, their exosomes, and Rexo-treated sensitive cells compared to their sensitive counterparts. On the other hand, miR-210-3p and miR-193b-3p were determined to be the two miRNAs which exhibited decreased expression profile in resistant cells and their exosomes compared to their sensitive counterparts. Gene targets, signaling pathways, and enrichment analysis were performed for these miRNAs by TargetScan, KEGG, and DAVID. Potential interactions between gene candidates at the protein level were analyzed via STRING and Cytoscape software. Our findings revealed CCR5, GRK2, EDN1, ARRB1, P2RY2, LAMC2, PAK3, PAK4, and GIT2 as novel gene targets that may play roles in exosomal imatinib resistance transfer as well as mTOR, STAT3, MCL1, LAMC1, and KRAS which are already linked to imatinib resistance. MDR1 mRNA exhibited higher expression in Rexo compared to Sexo as well as in K562S cells treated with Rexo compared to K562S cells which may suggest exosomal transfer of MDR1 mRNA.
  • [ X ]
    Öğe
    Methylsulfonylmethane induces caspase-dependent apoptosis in acute myeloid leukemia cell lines
    (2024) Hekmatshoar, Yalda; Karabay, Arzu Zeynep; Özkan, Tülin; Koç, Aslı; Sunguroğlu, Asuman
    Background: Acute myeloid leukemia (AML) is a heterogeneous ailment in both biological and clinical concepts. Numerous efforts have been devoted to discover natural compounds for combating cancer, which showed great potential in cancer management. Methylsulfonylmethane (MSM), an organosulfur dietary supplement, is utilized for improving various clinical conditions, particularly osteoarthritis. MSM can exert antitumor activity in a wide range of cancers. Objectives: The molecular mechanisms of action underlying antileukemic activity of MSM remain unclear. In this regard, we aimed to investigate the anticancer properties of MSM on human AML cell lines (U937 and HL60) with focus on underlying cell death mechanism. Methods: Anticancer activity of the MSM was examined employing MTT assay, Annexin V-PE/7AAD staining, caspase3/7 activity test, and real-time qPCR. Both cell lines were treated with different concentrations (50-400 mM) of MSM for 24 h. Pretreatment of the cells with a caspase inhibitor (i.e., Z-VAD-fmk) was performed for the assessment of apoptosis induction. Results: The results of MTT assay revealed that in both cell lines, the MSM markedly reduced cell viability in comparison to the control cells. Additionally, findings of Annexin V-7AAD staining revealed that MSM induced apoptosis and activated caspase 3/7 in both cell lines markedly. Real-time quantitative PCR results also supported the induction of apoptosis in AML cells. MSM altered the expression levels of various apoptotic genes (BAX, BAD, and BIM). Conclusion: Overall, our results indicated that MSM could induce apoptosis in AML cell lines in a dose-dependent manner, which therefore could be utilized as an antileukemic agent.
  • [ X ]
    Öğe
    Mitochondria-specific targeting to overcome imatinib resistance in chronic myeloid leukemia cells
    (Elsevier, 2024) Hekmatshoar, Yalda; Özkan, Tülin; Karabay, Arzu Zeynep; Koç, Aslı; Gürel, A. Karadağ; Vignais, Marie-Luce; Sunguroğlu, A.
    ...
  • [ X ]
    Öğe
    Nilotinib exhibits less toxicity than imatinib and influences the immune state by modulating iNOS, p-p38 and p-JNK in LPS/IFN gamma-activated macrophages
    (2023) Karabay, Arzu Zeynep; Özkan, Tülin; Koç, Aslı; Hekmatshoar, Yalda; Gürkan-Alp, A. Selen; Sunguroğlu, Asuman
    In this study, we aimed to analyze the effects of first and second-generation Bcr-Abl tyrosine kinase inhibitors, imatinib and nilotinib on LPS/IFN gamma activated RAW 264.7 macrophages. Our data revealed that imatinib was less effective on nitrite levels and more toxic on macrophages compared to nilotinib. Therefore, we further analysed the effect of nilotinib on various inflammatory markers including iNOS, COX-2, NFkB, IL-6, p-ERK, p-p38 and p-JNK in LPS/IFN gamma activated RAW264.7 macrophages. Spectrophotometric viability test and Griess assay,western blot, RT-PCR and luciferase reporter assays were used to analyze the biological activity of nilotinib. Our findings revealed that nilotinib decreases nitrite levels, iNOS mRNA, iNOS and p-p38 protein expressions significantly whereas induces IL-6 mRNA and p-JNK protein expressions at particular doses. We did not find significant effect of nilotinib on COX-2, p-ERK and nuclear p65 proteins and NFkB transcriptional activity. In addition, the binding mode of nilotinib to iNOS protein was predicted by molecular docking. According to the docking analyses, nilotinib exhibited hydrophobic interactions between MET349, ALA191, VAL346, PHE363, TYR367, MET368, CYS194, TRP366 residues at the binding pocket and the molecule as well as van der Waals interactions at specific residues. In conclusion, our results reveal that, in addition to its anticancer activity, nilotinib can exhibit immune modulatory effects on macrophages through its effects on iNOS, IL-6, p-p38 and p-JNK.
  • [ X ]
    Öğe
    Phenotypic and functional characterization of subpopulation of Imatinib resistant chronic myeloid leukemia cell line
    (2023) Hekmatshoar, Yalda; Karadağ Gürel, Aynur; Özkan, Tülin; Saadat, Yalda Rahbar; Koç, Aslı; Karabay, Arzu Zeynep; Bozkurt, Süreyya; Sunguroğlu, Asuman
    Purpose: Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the presence of BCR-ABL protein. Imatinib (IMA) is considered as the first line therapy in management of CML which particularly targets the BCR-ABL tyrosine kinase protein. However, emergence of resistance to IMA hinders its clinical efficiency. Hence, identifying novel targets for therapeutic approaches in CML treatment is of great importance. Here, we characterize a new subpopulation of highly adherent IMA-resistant CML cells that express stemness and adhesion markers compared to naive counterparts. Materials and methods: We performed several experimental assays including FISH, flow cytometry, and gene expression assays. Additionally, bioinformatics analysis was performed by normalized web-available microarray data (GSE120932) to revalidate and introduce probable biomarkers. Protein-protein interactions (PPI) network was analyzed by the STRING database employing Cytoscape v3.8.2. Results: Our findings demonstrated that constant exposure to 5 ​μM IMA led to development of the adherent phenotype (K562R-adh). FISH and BCR-ABL expression analysis indicated that K562R-adh cells were derived from the original cells (K562R). In order to determine the role of various genes involved in epithelial-mesenchymal transition (EMT) and stem cell characterization, up/down-regulation of various genes including cancer stem cell (CSC), adhesion and cell surface markers and integrins were observed which was similar to the findings of the GSE120932 dataset. Conclusion: Treating CML patients with tyrosine kinase inhibitors (TKIs) as well as targeting adhesion molecules deemed to be effective approaches in prevention of IMA resistance emergence which in turn may provide promising effects in the clinical management of CML patients.