TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article Prolonged Β-Hydroxybutyrate Ketosis Enhances Ponatinib Response of K562 Chronic Myeloid Leukaemia Cells(Dokuz Eylul Univ inst Health Sciences, 2025-01-31) Özkaya, Ali Burak; Geyik, Öykü Gönül; Malcanlı, SenanurPurpose: Ketosis is a metabolic state characterized by production of ketone bodies, including acetoacetate, β-hydroxybutyrate (BHB), and acetone, in response to reduced blood glucose levels. BHB stands out as the principal ketone body in nutritional ketosis which has diverse therapeutic implications for metabolic, nondegenerative and neoplastic disorders. In current study we investigated the impact of ketosis on chronic myeloid leukaemia (CML) cell viability and drug response. Materials and Methods: We investigated the impact of BHB-mediated ketosis on the viability of K562 cells, an in vitro model of CML, and explored the influence of BHB on the sensitivity of these cells to ponatinib, a multi-targeted tyrosine kinase inhibitor used in CML treatment. We used MTT assay to measure cell viability and Hoechst/PI assay to measure cell death. Results: Our findings reveal that BHB concentrations ranging from 1 mM to 5 mM, which fall within the physiological range of ketosis, elicit a minimal yet concentration-dependent reduction in cell viability. We also observed that while a 24-hour pre-treatment with BHB did not enhance the response of K562 cells to ponatinib, prolonged ketosis (4 days) improved response of cells to the drug by decreasing final cell viability from 25.15% to 13.12%. The primary mode of viability inhibition by ponatinib was cell death which was further intensified by exposure to prolonged ketosis. Conclusion: Ketosis induced by ketogenic diet of ketone body supplementation is considered as safe and effective adjuvant cancer therapy options and here, we report its potential effectiveness in the context of CML.Article Citation - WoS: 1Citation - Scopus: 1Differential Effects of Choline on TLR2/4 Mediated Signaling Through Possible Regulation of Toll-Interacting Protein in Hepatocellular Carcinoma Cell Lines(Walter de Gruyter GmbH, 2024-05-30) Barış, Elif; Demir, Ayse BanuObjectives: Toll-like receptor (TLR) mediated inflammatory status plays an important role in development and pro- gression of hepatocellular carcinoma (HCC). Toll-interacting protein (TOLLIP) has an inhibitory effect on TLR-mediated inflammatory signalling and expression profile of TOLLIP varies between malignancies including HCC. Cholinergic anti-inflammatory pathway (CAP) is an endogenous mech- anism that controls inflammatory status via α7nicotinic acetylcholine receptors (α7nAChR). This study aims to investigate the effect of CAP-acting agent choline on TOLLIP and its related TLR-mediated inflammatory response in HCC cells with distinct differentiation stages. Methods: The expression patterns of α7nAChR, TLR2/4, TOLLIP, IL6, NFkB genes were evaluated by RT-PCR and ELISA in the presence of choline, along with the real-time cell proliferation and migration in HEP3B and SNU449 HCC cell lines. The interaction between choline and TOLLIP assessed by using in-silico analyses. Results: Choline downregulated TOLLIP in Hep3B and SNU449 cells. However, the expressions of α7nAChR, NF-κB, IL-6, TLR2 and TLR4 showed a decreased pattern in well differentiated HEP3B cells, while an increased pattern in poorly differentiated SNU449 cells. Conclusions: Choline might exert differential effects in TLR2/4-dependent signalling based on the differentiation stages of the HCC cells, suggesting its potential therapeutic effects in earlier stages of HCC which might be result of its partial modulation of TOLLIP.Article Classification of Colon Cancer Patients Into Consensus Molecular Subtypes Using Support Vector Machines(2023-12-28) Koçhan, Necla; Dayanç, Barış EmreBackground/aim: The molecular heterogeneity of colon cancer has made classification of tumors a requirement for effective treatment. One of the approaches for molecular subtyping of colon cancer patients is the consensus molecular subtypes (CMS), developed by the Colorectal Cancer Subtyping Consortium. CMS-specific RNA-Seq-dependent classification approaches are recent, with relatively low sensitivity and specificity. In this study, we aimed to classify patients into CMS groups using their RNA-seq profiles. Materials and methods: We first identified subtype-specific and survival-associated genes using the Fuzzy C-Means algorithm and log- rank test. We then classified patients using support vector machines with backward elimination methodology. Results: We optimized RNA-seq-based classification using 25 genes with a minimum classification error rate. In this study, we reported the classification performance using precision, sensitivity, specificity, false discovery rate, and balanced accuracy metrics. Conclusion: We present a gene list for colon cancer classification with minimum classification error rates and observed the lowest sensitivity but the highest specificity with CMS3-associated genes, which significantly differed due to the low number of patients in the clinic for this group.Article ?-Hydroxybutyrate Does Not Influence Viability and Clonogenicity of A549 Lung Cancer Cells(2023-03-15) Özkaya, Ali Burak; Malcanlı, Semanur; Geyik, Öykü GönülBackground/Purpose: The metabolic shift from catabolism of carbohydrates to lipids results in production of ketone bodies leading to a state called ketosis. Ketosis via ketone supplement or ketogenic diet has been proposed as a non-toxic therapeutic option for a broad range of malignancies. Although the clinical impact of ketogenic diet is well-documented, the effect of ketone bodies on cancer cell biology is not clear for some cancers including non-small-cell lung cancer (NSCLC). In this study, we aimed to demonstrate the effects of the most prominent ketone body, ?-hydroxybutyrate, on a NSCLC cell line, A549. Methods: A549 cell line was utilized as the in vitro model in this study. The effects of different ?-hydroxybutyrate concentrations on cell viability were measured via sulphorodamine-B (SRB) viability assay. Long term effects of ketosis were evaluated via colony formation assay. Finally, the effect of ?-hydroxybutyrate on cell migration was determined via scratch assay. Results: Our results suggest that introduction of ?-hydroxybutyrate in physiologically relevant concentrations into the cell culture media does not influence cell viability, clonogenicity or migration. Conclusion: ?-hydroxybutyrate has been previously demonstrated to induce, inhibit or does not influence the viability of different cell lines but there is no report regarding its effects on NSCLC cells. Here we report that physiologically relevant concentrations of ?-hydroxybutyrate have no effect on viability, clonogenicity and migration of A549 cells.Article Citation - WoS: 1Citation - Scopus: 1Shotgun Lipidomics Elucidates the Lipidome Alterations of the Mcl-1 Inhibitor S63845 in Aml Cell Lines With a Focus on Sphingolipids(Istanbul University Press, 2022-12-30) Yandım, Melis Kartal; Bilgin, MesutObjective: Acute myeloid leukemia (AML) is a vigorous type of leukemia requiring effective treatment. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic molecule that is upregulated in AML and is studied as a target for treatment. The specific Mcl-1 inhibitor, S63845, has antiproliferative effects on AML cells. Bioactive sphingolipids have crucial roles in cells and regulate Mcl-1 stability. This study aimed to elucidate the changes in lipid profiles of AML cell lines in response to Mcl-1 inhibitor S63845 treatment, with a special focus on sphingolipids. Materials and Methods: The cytotoxic effects of S63845 were identified in the AML cell lines MV4-11, HL60, and KG1 using the MTT cell proliferation assay. Lipidome analysis was conducted by quantitative shotgun lipidomics covering 378 individual lipid species in 26 classes within the major lipid categories. Results: The IC50 values of S63845 have been calculated as 7 nM for MV4-11, 53 nM for HL60, and 479 nM for KG1. The lipidome results reveal the S63845 treatment to increase ceramide (Cer) levels in the MV4-11 and KG1 cell lines at the expense of downstream sphingolipids while increasing the hexosylceramide (HexCer) levels in the HL60 cell line at the expense of the Cer and sphingomyelin (SM). Conclusion: This study showed S63845 to be able to suppress cell proliferation by altering lipid compositions in AML cell lines. More importantly, the study suggested S63845 to differentially affect the lipid profiles of AML cell lines.Article Epigenetic Basis of Twin Discordance in Diseases: Future Benefits(2018) Demir, Ayşe Banu; Demir, NamıkMonozygotic twins share the same genotype since they are derived from the same zygote. However,monozygotic twin siblings frequently present many phenotypic differences, such as their susceptibilitiesto diseases. These isogenic individuals are not entirely identical. They exhibit phenotypic incompatibilityfor many features, from birth weight to complex diseases. Recently, several studies have been publishedshowing that phenotypic differences, especially in monozygotic twins, are being induced from prenatalperiod to life-long epigenetic differences. Epigenetic studies on twins have a great potential to contributeto our understanding of complex diseases, such as cancer, autoimmune disorders, psychiatric disordersand neurological diseases. Since monozygotic twins are genetic clones (genetically identical), they areconsidered as perfect models for studying the role of environmental factors as determinants of complexdiseases and phenotypes. In this review, a number of intrauterine effects and genetic mechanisms thatmay affect phenotypic, genotypic, and epigenetic differences between monozygotic twins were describedand effects of epigenetic mechanisms on complex diseases were mentioned. Further work on epigeneticchanges in diseases using incompatible monozygotic twin models, would lead to new developments inmedical therapies.Article Meme Kanseri Hücre Hatlarında Propranolol ve Paklitakselin Anjiyogenez Üzerine Etkisi(2019-03-31) Vatansever, H. Seda; Tuğlu, İbrahim; Özbilgin, Kemal; İnan, Sevinç; Şimşek, Fatma; Müftüoğlu, Sevda; Tuğlu, Mehmet İbrahim; Vatansever, SedaAmaç: Bu çalışmanın amacı infantil hemanjiyomvakalarında kullanılan propranolol (PR) ile kemoterapötikbir ajan olarak yaygın kullanılan Paklitakselin (PX) kanserhücreleri üzerine etkisini incelenmesidir.Gereç ve Yöntem: Tripan mavisi ile hücre sayımıyapılarak hücrelerin ikilenme zamanları belirlendi. MTTtesti ile de ilaçların sitotoksik etkisi ve IC50 değerleri analizedildi. İnvazyon yönünden farklı iki meme kanseri hücrehattında (MDA-MB-231 ve MCF-7) anti-VEGF, antieNOS, anti-iNOS ve anti-ERK1/2 primer antikorlarıindirek immunohistokimyasal yöntemle incelendi.İmmunoreaktivitenin değerlendirilmesi için H skorlamasistemi kullanıldı.Bulgular: MTT testi ile hücrelere uygulanacak ilaçdozlarının IC50 değerleri MDA için; PX: 5 nmol, PR: 50µm ve MCF- 7 için; PX: 3,7 nmol, PR: 50 µm olarakbulundu. İmmunohistokimyasal uygulamada kanserhücrelerinde kontrol gruplarının immunoreaktivitesişiddetli ve/veya çok şiddetli artmış iken PX, PR vekombine uygulanan ilaç gruplarında boyanma şiddetianlamlı veya çok anlamlı olarak azaldı.Sonuç: Bu çalışma ile kemoterapötik olarak uygulananpaklitaksele ek olarak anti anjiyogenik ilaç uygulamalarınındamarlarda vazodilatasyon, hücre çoğalması, göçü veyaşam süresini etkilemesi sonucunda anjiyogeneziazaltması veya önlemesi açısından meme kanserinintedavisinde önemli olduğu düşünülmüştür.Article Citation - WoS: 6Citation - Scopus: 5Acrylamide-Encapsulated Glucose Oxidase Inhibits Breast Cancer Cell Viability(Walter De Gruyter Gmbh, 2020-08-04) Rrustemi, Trendelina; Geyik, Oyku Gonul; Ozkaya, Ali Burak; Ozturk, Taylan Kurtulus; Yuce, Zeynep; Kilinc, AliObjectives: Cancer cells modulate metabolic pathways to ensure continuity of energy, macromolecules and redoxhomeostasis. Although these vulnerabilities are often targeted individually, targeting all with an enzyme may prove a novel approach. However, therapeutic enzymes are prone to proteolytic degradation and neutralizing antibodies leading to a reduced half-life and effectiveness. We hypothesized that glucose oxidase (GOX) enzyme that catalyzes oxidation of glucose and production of hydrogen peroxide, may hit all these targets by depleting glucose; crippling anabolic pathways and producing reactive oxygen species (ROS); unbalancing redox homeostasis. Methods: We encapsulated GOX in an acrylamide layer and then performed activity assays in denaturizing settings to determine protection provided by encapsulation. Afterwards, we tested the effects of encapsulated (enGOX) and free (fGOX) enzyme on MCF-7 breast cancer cells. Results: GOX preserved 70% of its activity following encapsulation. When fGOX and enGOX treated with guanidinium chloride, fGOX lost approximately 72% of its activity, while enGOX only lost 30%. Both forms demonstrated remarkable resilience against degradation by proteinase K and inhibited viability of MCF-7 cells in an activity-dependent manner. Conclusions: Encapsulation provided protection to GOX against denaturation without reducing its activity, which would prolong half-life of the enzyme when administered intravenously.Article Citation - WoS: 7An in Vitro Study in Which New Boron Derivatives Maybe an Option for Breast Cancer Treatment(Kare Publ, 2019) Simsek, Fatma; Inan, Sevinc; Korkmaz, MehmetObjectives: We aimed to investigate the distribution of immunoreactivities of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and inducible NOS (iNOS) on breast cancer cells in response to treatment with boron derivatives. Methods: We initially analyzed the cytotoxic effect and IC50 value of boron by MTT assay. For the evaluation of the angiogenesis, expression level of antibodies was detected to following boron derivatives such as boric acid, boron penta (BP), and T-Boron (DPD) in the absence of boron treatment using the indirect immunohistochemical method.The evaluation of these staining was done using the H-scoring system. Results: It was found that immunoreactivities of VEGF, eNOS, and iNOS increased on control compared to those of the cells of MDA-MB231 human breast cancer cell line. Following boron derivatives treatment, it was observed that they were inhibited the VEGF/NOS labeling in MDA-MB-231 breast cancer cells. Conclusion: The present data suggest that BP, especially DPD, inhibits the angiogenesis of breast cancer cells through VEGF pathway. From this point, these boron derivatives may provide a novel therapeutic approach for breast cancer treatment.