Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 28Citation - Scopus: 29Revealing Genome-Wide Mrna and Microrna Expression Patterns in Leukemic Cells Highlighted “hsa-Mir as a Tumor Suppressor for Regain of Chemotherapeutic Imatinib Response Due To Targeting Stat5a(SAGE Publications Inc., 2015) Tezcanlı Kaymaz, Burçin; Selvi Günel, Nur; Ceyhan, Metin; Bozok Çetintaş, Vildan; Özel, Buket; Kartal Yandım, Melis; Kıpçak, Sezgi; Aktan, Çağdaş; Adan Gökbulut, Aysun; Baran, Yusuf; Kosova Can, BuketBCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNAArticle Citation - WoS: 20Citation - Scopus: 23Apoptotic Effects of Non-Edible Parts of Punica Granatum on Human Multiple Myeloma Cells(SAGE Publications Inc., 2016) Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, YusufMultiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.Article Citation - WoS: 6Citation - Scopus: 6A Molecular and Biophysical Comparison of Macromolecular Changes in Imatinib-Sensitive and Imatinib-Resistant K562 Cells Exposed To Ponatinib(SAGE Publications Inc., 2016) Kartal Yandım, Melis; Ceylan, Çağatay; Elmas, Efe; Baran, YusufChronic myeloid leukemia (CML) is a type of hematological malignancy that is characterized by the generation of Philadelphia chromosome encoding BCR/ABL oncoprotein. Tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib, are used for the frontline therapy of CML. Development of resistance against these TKIs in the patients bearing T315I mutation is a major obstacle in CML therapy. Ponatinib, the third-generation TKI, is novel drug that is effective even in CML patients with T315I mutation. The exact mechanism of ponatinib in CML has been still unknown. In this study, we aimed to determine the potential mechanisms and structural metabolic changes activated by ponatinib treatment in imatinib-sensitive K562 human CML cell lines and 3 μM-imatinib-resistant K562/IMA3 CML cell lines generated at our lab. Apoptotic and antiproliferative effects of ponatinib on imatinib-sensitive and 3 μM-imatinib-resistant K562/IMA3 CML cells were determined by proliferation and apoptosis assays. Additionally, the effects of ponatinib on macromolecules and lipid profiles were also analyzed using Fourier transform infrared spectroscopy (FTIR). Our results revealed that ponatinib inhibited cell proliferation and induced apoptosis as determined by loss of mitochondrial membrane potential, increased caspase-3 enzyme activity, and transfer of phosphatidylserine to the plasma membrane in both K562 and K562/IMA-3 cells. Furthermore, cell cycle analyses revealed that ponatinib arrested K562 and K562/IMA-3 cells at G1 phase. Moreover, ponatinib treatment created a more ordered nucleic acid structure in the resistant cells. Although the lipid to protein ratio increased in imatinib-sensitive K562 cells with a little decrease in the K562/IMA-3 cells, ponatinib treatment indicated significant changes in the lipid composition such as a significant increase in the cellular cholesterol amounts much more in the K562/IMA-3 cells than the sensitive counterparts. Unsaturation in lipids was higher in the resistant cells; however, increases in lipids without phosphate and the number of acyl chains were much higher in the K562 cells. Taken together, all these results showed powerful antiproliferative and apoptotic effects of ponatinib in both imatinib-sensitive and imatinib-resistant CML cells in a dose-dependent manner, and hence, the use of ponatinib for the treatment of TKI-resistant CML patients may be an effective treatment approach in the clinic. More importantly, these results showed that FTIR spectroscopy can detect drug-induced physiological changes in cancer drug resistance.Article Citation - WoS: 43Citation - Scopus: 49The Pleiotropic Effects of Fisetin and Hesperetin on Human Acute Promyelocytic Leukemia Cells Are Mediated Through Apoptosis, Cell Cycle Arrest, and Alterations in Signaling Networks(SAGE Publications Inc., 2015) Adan, Aysun; Baran, YusufFisetin and hesperetin, flavonoids from various plants, have several pharmaceutical activities including antioxidative, anti-inflammatory, and anticancer effects. However, studies elucidating the role and the mechanism(s) of action of fisetin and hesperetin in acute promyelocytic leukemia are absent. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by fisetin and hesperetin on human HL60 acute promyelocytic leukemia cells. The viability of HL60 cells was evaluated using the MTT assay, apoptosis by annexin V/propidium iodide (PI) staining and cell cycle distribution using flow cytometry, and changes in caspase-3 enzyme activity and mitochondrial transmembrane potential. Moreover, we performed whole-genome microarray gene expression analysis to reveal genes affected by fisetin and hesperetin that can be important for developing of future targeted therapy. Based on data obtained from microarray analysis, we also described biological networks modulated after fisetin and hesperetin treatment by KEGG and IPA analysis. Fisetin and hesperetin treatment showed a concentration- and time-dependent inhibition of proliferation and induced G2/M arrest for both agents and G0/G1 arrest for hesperetin at only the highest concentrations. There was a disruption of mitochondrial membrane potential together with increased caspase-3 activity. Furthermore, fisetin- and hesperetin-triggered apoptosis was confirmed by annexin V/PI analysis. The microarray gene profiling analysis revealed some important biological pathways including mitogen-activated protein kinases (MAPK) and inhibitor of DNA binding (ID) signaling pathways altered by fisetin and hesperetin treatment as well as gave a list of genes modulated ≥2-fold involved in cell proliferation, cell division, and apoptosis. Altogether, data suggested that fisetin and hesperetin have anticancer properties and deserve further investigation.Article Citation - WoS: 15Citation - Scopus: 11T Cells in Tumor Microenvironment(SAGE Publications Inc., 2016) Kiraz, Yağmur; Baran, Yusuf; Nalbant, AytenTumors progress in a specific area, which supports its development, spreading or shrinking in time with the presence of different factors that effect the fate of the cancer cells. This specialized site is called “tumor microenvironment” and has a composition of heterogenous materials. The immune cells are also residents of this stromal, cancerous, and inflammatory environment, and their types, densities, or functional differences are one of the key factors that mediate the fate of a tumor. T cells as a vital part of the immune system also are a component of tumor microenvironment, and their roles have been elucidated in many studies. In this review, we focused on the immune system components by focusing on T cells and detailed T helper cell subsets in tumor microenvironment and how their behaviors affect either the tumor or the patient’s outcome. © 2015, International Society of Oncology and BioMarkers (ISOBM).Article Citation - WoS: 6Citation - Scopus: 7Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion(SAGE Publications Inc., 2015) Katgı, Abdullah; Sevindik, Ömer Gökmen; Adan Gökbulut, Aysun; Özsan, Güner Hayri; Yüksel, Faize; Solmaz, Şerife Medeni; Alacacıoğlu, İnci; Özcan, Mehmet Ali; Demirkan, Fatih; Baran, Yusuf; Pişkin, ÖzdenBackground: There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. Objectives: In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. Methods: 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. Results: There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. Conclusion: Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability.Article Citation - WoS: 13Citation - Scopus: 13Macromolecular Changes in Nilotinib Resistant K562 Cells; an in Vitro Study by Fourier Transform Infrared Spectroscopy(SAGE Publications Inc., 2012) Ceylan, Çağatay; Camgöz, Aylin; Baran, YusufNilotinib is a second generation tyrosine kinase inhibitor which is used in both first and second line treatment of chronic myeloid leukemia (CML). In the present work, the effects of nilotinib resistance on K562 cells were investigated at the molecular level using Fourier transform infrared (FT-IR) spectroscopy. Human K562 CML cells were exposed to step-wise increasing concentrations of nilotinib, and sub-clones of K562 cells resistant to 50 nM nilotinib were generated and referred to as K562/NIL-50 cells. Antiproliferative effects of nilotinib were determined by XTT cell proliferation assay. Changes in macromolecules in parental and resistant cells were studied by FT-IR spectroscopy. Nilotinib resistance caused significant changes which indicated increases in the level of glycogen and membrane/lipid order. The amount of unsaturated lipids increased in the nilotinib resistant cells indicating lipid peroxidation. The total amount of lipids did not change significantly but the relative proportion of cholesterol and triglycerides altered considerably. Moreover, the transcriptional status decreased but metabolic turn-over increased as revealed by the FT-IR spectra. In addition, changes in the proteome and structural changes in both proteins and the nucleus were observed in the K562/NIL-50 cells. Protein secondary structural analyses revealed that alpha helix structure and random coil structure decreased, however, anti-parallel beta sheet structure, beta sheet structure and turns structure increased. These results indicate that the FT-IR technique provides a method for analyzing drug resistance related structural changes in leukemia and other cancer types.