Browsing by Author "Gokbulut, Aysun Adan"

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Citation Count: 42
Bioactive, functional and edible film-forming properties of isolated hazelnut (Corylus avellana L.) meal proteins
(Elsevier Sci Ltd, 2014) Aydemir, Levent Yurdaer; Gokbulut, Aysun Adan; Baran, Yusuf; Yemenicioglu, Ahmet; Baran, Yusuf
This study aimed characterization of bioactive, functional and edible film making properties of isolated proteins from untreated (HPI), hot extracted (HPI-H), acetone washed (HPI-AW), and acetone washed and hot extracted (HPC-AW-H) hazelnut meals. The most bioactive protein extract was HPC-AW-H, followed by HPI-AW, HPI-H and HPI, based on antioxidant activity (TEAC and ORAC: 158-461 mmol Trolox/kg), iron chelation (60.7-126.7 mmol EDTA/kg), angiotensin-converting enzyme inhibition (IC50: 0.57-1.0 mg/mL) and antiproliferative activity on colon cancer cells (IC50: 3.0-4.6 mg/ml). Protein contents of HPI, HPI-H and HPI-AW (93.3-94.5%) were higher than that of HPC-AW-H (86.0%), but HPC-AW-H showed the best pH-solubility profile. The extracts showed good oil absorption (7.4-9.4 g/g) and foaming, but limited water holding and gelling capacities, and emulsion stability. The protein extracts gave transparent, yellowish to brownish and reddish colored and water soluble edible films. The HPI gave the lightest colored films with acceptable mechanical properties (elongation up to 144% and tensile strength up to 4.9 MPa). 1-D and 2-D electrophoresis clearly showed the molecular and isoelectric profiles of hazelnut proteins. The overall results of this study showed that the bioactive, solubility and gelation properties of hazelnut proteins could be improved by simple processes like acetone washing and/or heat treatment. The hazelnut proteins are valuable as multipurpose food ingredients. (c) 2013 Elsevier Ltd. All rights reserved.
Citation Count: 5
Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion
(Sage Publications inc, 2015) Katgi, Abdullah; Sevindik, Omur Gokmen; Gokbulut, Aysun Adan; Ozsan, Guner Hayri; Yuksel, Faize; Solmaz, Serife Medeni; Piskin, Ozden
Background: 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.
Citation Count: 2
A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells
(Galenos Yayincilik, 2015) Gokbulut, Aysun Adan; Yasar, Mustafa; Baran, Yusuf; Baran, Yusuf
Objective: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, Izmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. Materials and Methods: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. Results: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. Conclusion: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.
Citation Count: 54
Resveratrol and quercetin-induced apoptosis of human 232B4 chronic lymphocytic leukemia cells by activation of caspase-3 and cell cycle arrest
(Taylor & Francis Ltd, 2013) Gokbulut, Aysun Adan; Apohan, Elif; Baran, Yusuf; Baran, Yusuf
Chronic lymphocytic leukemia (CLL), defined by accumulation of pathogenic B cells, has a very complex biology due to various factors such as inherited, host, and enviromental factors. Recently, finding new therapeutic agents or development of novel treatment strategies have been paid attention. Resveratrol and quercetin, important phytoalexins found in many plants, have been reported to have cytotoxic effects on various types of cancer. In this study, we examined cytotoxic, cytostatic, and apoptotic effects of these two important phenolic compounds on 232B4 human CLL cells. Cytotoxic effects of resveratrol and quercetin were determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using caspase-3 colorimetric assay. Annexin V-FITC/PI double staining was performed to measure apoptotic cell population. Effects of resveratrol and quercetin on cell cycle profiles of CLL cells were investigated by flow cytometry. Treatment of CLL cells with resveratrol and quercetin caused dose dependent inhibition of cell proliferation and increased apoptotic cell population through induction of caspase-3 activity. Cell cycle analysis displayed cell cycle arrest mainly in G0/G1 for both polyphenols. Our data, in total, showed for the first time that resveratrol and quercetin might block CLL growth through inducing apoptosis and cell cycle arrest.
Citation Count: 12
STAT pathway in the regulation of zoledronic acid-induced apoptosis in chronic myeloid leukemia cells
(Elsevier France-editions Scientifiques Medicales Elsevier, 2013) Kiper, Hatice Demet; Kaymaz, Burcin Tezcanli; Gokbulut, Aysun Adan; Selvi, Nur; Avci, Cigir Biray; Kosova, Buket; Saydam, Guray
In this study, we aimed to evaluate the cytotoxic and apoptotic effects of zoledronic acid on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on zoledronic acid-induced apoptosis. The results showed that zoledronic acid decreased proliferation, and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT3, -5A and -5B genes were significantly reduced in zoledronic acid-treated K562 cells. These data indicated that STAT inhibition by zoledronic acid may be therapeutic in CML patients following the confirmation with clinical studies. (C) 2013 Elsevier Masson SAS. All rights reserved.
Citation Count: 16
Suppression of STAT5A and STAT5B chronic myeloid leukemia cells via siRNA and antisense-oligonucleotide applications with the induction of apoptosis
(E-century Publishing Corp, 2013) Kaymaz, Burcin Tezcanli; Selvi, Nur; Gokbulut, Aysun Adan; Aktan, Cagdas; Gunduz, Cumhur; Saydam, Guray; Kosova, Buket
Signal transducers and activators of transcription ( STAT) proteins function in the JAK/STAT signaling pathway and are activated by phosphorylation. As a result of this signaling event, they affect many cellular processes including cell growth, proliferation, differentiation, and survival. Increases in the expressions of STAT5A and STAT5B play a remarkable role in the development of leukemia in which leukemic cells gain uncontrolled proliferation and angiogenesis ability. At the same time, these cells acquire ability to escape from apoptosis and host immune system. In this study, we aimed to suppress STAT-5A and -5B genes in K562 CML cells by siRNA transfection and antisense oligonucleotides (ODN) targeting and then to evaluate apoptosis rate. Finally, we compared the transfection efficiencies of these approaches. Quantitative RT-PCR and Western blot results indicated that STAT expressions were downregulated at both mRNA and protein levels following siRNA transfection. However, electroporation mediated ODN transfection could only provide limited suppression rates at mRNA and protein levels. Moreover, it was displayed that apoptosis were significantly induced in siRNA treated leukemic cells as compared to ODN treated cells. As a conclusion, siRNA applications were found to be more effective in terms of gene silencing when compared to ODN treatment based on the higher apoptosis and mRNA suppression rates. siRNA application could be a new and alternative curative method as a supporting therapy in CML patients.
Citation Count: 27
Therapeutic Potential of Apigenin, a Plant Flavonoid, for Imatinib-Sensitive and Resistant Chronic Myeloid Leukemia Cells
(Routledge Journals, Taylor & Francis Ltd, 2014) Solmaz, Soner; Gokbulut, Aysun Adan; Cincin, Birsu; Ozdogu, Hakan; Boga, Can; Cakmakoglu, Bedia; Baran, Yusuf; Baran, Yusuf
Despite the presence of many therapeutic regimens like imatinib and other tyrosine kinase inhibitors, the development of resistance, intolerance, and side effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is a need to discover novel drugs for CML patients. In this study, we attempted to assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic, apoptotic, and cytostatic effects on imatinib-sensitive and resistant Philadelphia-positive CML cells. We analyzed apigenin's effects on cell proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore, we described genes and gene networks that are modulated in CML in response to apigenin. Results of our study revealed that apigenin has cytotoxic and apoptotic effects on both cell types. We also displayed that apigenin induced G2/M arrest in K562 cells while arresting K562/IMA3 cells in S phase especially at the highest apigenin concentration. The expression analysis identified a set of genes that were regulated by apigenin in K652 and K562/IMA3 cells. Association of modulated genes with biological functional groups identified several networks affected by apigenin including cell survival, proliferation, cell death, cell cycle, and cell signalling pathways.