Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Conference Object Targeting Sphingosine Kinase-1/Spingosine-1-phosphate Receptor 2 Signalling Pathway To Overcome T315i Mutation in 32dcl3 Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Öğretmen, Besim; Baran, YusufThe main problem in chronic myeloid leukemia patients is the development of resistance against tyrosine kinase inhibitors. The expression of BCR-ABL1 having T315 mutation is responsible for the development of nilotinib resistance. The alterations in sphingolipid signalling pathway is a significant BCR-ABL1-dependent resistance mechanism. Recently, we showed that sphingosine kinase-1 (SK-1)/sphingosine-1 phosphate (S1P)-mediated drug resistance is transduced via sphingosine-1 phosphate receptor 2 (S1P2) that inhibits protein phosphatase 2A (PP2A), causing increased stability of BCR-ABL1. However, specific signaling cascade involved in this process remain unkown. In this study, BCR-ABL1 expressing 32Dcl3 cells, 32D-p210Bcr-Abl(wt) and 32D-p210Bcr-Abl (T315I) were used. The antiproliferative effects of nilotinib, SK-1 inhibitor (PF-543), S1P2 inhibitor (JTE-013), phospholipase C inhibitor (U-73122) and nilotinib/PF-543 and nilotinib/JTE-013 combinations on wt and resistant cells were determined by MTT assay. Isobologram analysis was performed using CompuSyn program.Conference Object Therapeutic Potential of Fisetin, Vitexin and Hesperetin on Chronic Myeloid Leukemia Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Baran, YusufIn Chronic Myeloid Leukemia (CML) treatment, despite therapeutic efficacy of tyrosine kinase inhibitors, resistance development and side effects cause problems. Fisetin, vitexin and hesperetin are plant-derived flavonoids. In this study, therapeutic potentials of fisetin, vitexin and hesperetin were determined in CML cells. Cytotoxic effects of flavonoids were determined by MTT assay while apoptotic effects were determined by changes in caspase- 3 activity, loss of mitochondrial membrane potential (MMP) and Annexin V/PI double staining. Cytostatic effects of the flavonoids were evaluated by propidium iodide staining using flow cytometry.Conference Object A Novel Biomarker for Drug Resistance in Chronic Myeloid Leukemia: Microrna-17(Elsevier Ltd., 2014) Baran, Yusuf; Fıratlıgil, Burcu; Kartal Yandım, Melis; Kiraz, Yağmur; Kozanoğlu, İlknur; Özdoğu, Hakan; Ünal, AlimiRNAs are single stranded small RNA molecules (20–22 nt), which do not have ability to code for proteins. These types of RNAs play significant roles on gene regulation through inhibition of their target genes. In animals, most of miRNAs show their translational inhibitor effect on target mRNAs by semi-complementation to 3’UTR sequences of mRNAs and deadenylation that cause degradation of these mRNAs. The importance of miRNAs is increasing in cancer diagnosis and treatment since they are one of the major regulators of genes such as oncogenes, tumor suppressor genes. miR-17 is an oncogenic miRNA that suppress the activation of tumor suppressor genes like CDKN1A, p21 and E2F1. Based on previous information, we aimed to determine the correlation between expression levels of miR-17 microRNA in newly diagnosed, tyrosine kinase inhibitors treated and drug resistant CML patients.Conference Object Cytotoxic and Apoptotic Effects of Fisetin, Hesperetin and Vitexinon Acute Promyelocytic Leukemia Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Baran, YusufAcute Promyelocytic Leukaemia (APL) is characterized by abnormal accumulation of immature granulocytes in the bone marrow and the blood stream. To date, there is no definitive treatment strategy. Fisetin, hesperetin and vitexin are flavanoids found in fruits and vegetables. Their anticancer properties have been studied on several cancer types. In this study, we aimed to examine the cytotoxic, cytostatic and apoptotic effects of fisetin, hesperetin and vitexin on Acute Promyelocytic Leukaemia cells. Cytotoxic effects were evaluated by MTT assay while apoptotic effects of these flavonoids were examined by changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and Annexin V/PI double staining. Cytostatic effects of the flavonoids were evaluated by propidium iodide staining using flow cytometry.Article Citation - WoS: 51Citation - Scopus: 58Synthesis, Cytotoxic and Antimicrobial Activities of Novel Cobalt and Zinc Complexes of Benzimidazole Derivatives(Elsevier Ltd., 2017) Apohan, Elif; Yılmaz, Ülkü; Yılmaz, Özgür; Serindağ, Ayfer; Küçükbay, Hasan; Yeşilada, Özfer; Baran, YusufIn this study fourteen novel cobalt (II) or zinc (II) complexes of benzimidazoles were synthesized from the 1-(4-substitutedbenzyl)-1H-benzimidazoles and CoCl2·6H2O or ZnCl2. Cytotoxic activities of novel complexes were investigated against lung cancer cells (A549) and BEAS-2B. Three of the examined compounds (1, 4 and 5) showed high cytotoxic activity against A549. While the IC50 of the cisplatin was 2.56 μg/mL for A549 cells at 72 h, the IC50 values of compounds 1, 4 and 5 were 1.97, 1.87 and 1.9 μg/mL, respectively. IC50 values of these compounds for BEAS-2B cells were higher than the IC50 values for A549. While the IC50 values for BEAS-2B cells were 59.8, 24.5 and 32.67 μg/mL, respectively, the IC50 of the cisplatin was determined as 2.53 μg/mL in the present work. Three of the compounds have also high antimicrobial activity against all the microorganisms used.Article Citation - WoS: 56Citation - Scopus: 66Molecular Mechanisms of Quercitrin-Induced Apoptosis in Non-Small Cell Lung Cancer(Elsevier Ltd., 2014) Çinçin, Zeynep Birsu; Ünlü, Miray; Kıran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Çakmakoğlu, BediaBackground and Aims: Quercitrin (QR; quercetin-3-O-rhamnoside) has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. Furthermore, it was demonstrated that quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. However, the mechanisms of quercitrin effects on cancer cell proliferation and apoptosis is not well understood. The aim of this study is to investigate the cytotoxic and apoptotic effects of quercitrin and the molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer (NSCLC) cell lines. Methods: Time- and dose-dependent antiproliferative and apoptotic effects of quercitrin determined by WST-1cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, determination of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine in the plasma membrane. Changes in whole genome gene expression levels were examined by Illumina Human HT-12v4 beadchip microarrays. Results: There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to quercitrin in A549 and NCI-H358 NSCLC cells in a time- and dose-dependent manner. Conclusion: Our results demonstrated that genes involved in leukocyte transendothelial migration, cell adhesion and phosphatidylinositol signaling system pathways were the most statistically significant pathways in NCI-H358 and A549cells. These results revealed that quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. After confirming its anticarcinogenic effects invivo, quercitrin could be a novel and strong anticancer agent against NSCLC.Article Citation - WoS: 5Citation - Scopus: 5Targeting Foxm1 Transcription Factor in T-Cell Acute Lymphoblastic Leukemia Cell Line(Elsevier Ltd., 2015) Tüfekçi, Özlem; Kartal Yandım, Melis; Ören, Hale; İrken, Gülersu; Baran, YusufThe Forkhead box protein M1 (FoxM1) is an important transcription factor having significant roles in various cellular events. FoxM1 overexpression has been reported to be related with many types of cancer. However, it is not known whether it contributes to oncogenesis of acute lymphoblastic leukemia. Siomycin A, a thiazol antibiotic, is known to inhibit FoxM1 transcriptional activity. In this study, we aimed to determine gene expression levels of FoxM1 in Jurkat cells (T-cell acute lymphoblastic leukemia cell line) and therapeutic potential of targeting FoxM1 by siomycin A alone and in combination with dexamethasone which improves the survival of children with T-cell acute lymphoblastic leukemia (ALL). We also examined the molecular mechanisms of siomycin A and dexamethasone-induced cell death in Jurkat cells. We demonstrated that FoxM1 mRNA is highly expressed in Jurkat cells. Dexamethasone and siomycin A caused a significant reduction in gene expression levels of FoxM1 in Jurkat cells. Targeting FoxM1 by siomycin A and dexamethasone caused a significant decrease in T-ALL cell line proliferation through induction of G1 cell cycle arrest. All these findings suggest a possible role of FoxM1 in T-cell ALL pathogenesis and represent FoxM1 as an attractive target for T-cell ALL therapy. © 2014 Elsevier Ltd.Article Citation - WoS: 49Citation - Scopus: 66Bioactive, Functional and Edible Film-Forming Properties of Isolated Hazelnut (corylus Avellana L.) Meal Proteins(Elsevier Ltd., 2014) Aydemir, Levent Yurdaer; Adan Gökbulut, Aysun; Baran, Yusuf; Yemenicioğlu, AhmetThis 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: 158-461mmolTrolox/kg), iron chelation (60.7-126.7mmolEDTA/kg), angiotensin-converting enzyme inhibition (IC50: 0.57-1.0mg/mL) and antiproliferative activity on colon cancer cells (IC50: 3.0-4.6mg/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 (7.4-9.4g/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 4.9MPa). 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.Article Citation - WoS: 79Citation - Scopus: 84An Update on Molecular Biology of Thyroid Cancers(Elsevier Ltd., 2014) Ömür, Özgür; Baran, YusufDifferentiated thyroid cancer (DTC) is the most common endocrinological malignancy. There are several histological variants such as papillary and follicular thyroid carcinoma. Many patients with well-differentiated subtypes of DTC are cured by surgery alone or with radioiodine, while poorly differentiated types usually have a worse prognosis. The aggressiveness of thyroid tumors is closely linked to specific gene alterations.Several diagnostic and prognostic molecular markers such as BRAF and RAS point mutations; RET/PTC and PAX8/PPARγ gene rearrangements; MAPK, PI3K, p53, Wnt-beta catenin, HIF1α and NF-kappaB signaling pathways; microRNA profiles and aberrant methylation have been demonstrated in more than 70% of DTC. Diagnostic use of these molecular markers may be optimized for identifying higher risks of mortality, tumor recurrence and metastatic potential. Understanding the molecular biology of thyroid cancers can be an important avenue for diagnosis and treatment of radioiodine-refractory or inoperable DTC patients with novel molecular targeted therapeutic agents. © 2014 Elsevier Ireland Ltd.Article Citation - WoS: 13Citation - Scopus: 13Stat Pathway in the Regulation of Zoledronic Acid-Induced Apoptosis in Chronic Myeloid Leukemia Cells(Elsevier Ltd., 2013) Kiper, Hatice Demet; Tezcanlı Kaymaz, Burçin; Adan Gökbulut, Aysun; Selvi, Nur; Biray Avcı, Çığır; Kosova, Buket; İskender, Güniz; Kartal Yandım, Melis; Gündüz, Cumhur; Şahin, Fahri; Baran, Yusuf; Saydam, GürayIn 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. © 2013 Elsevier Masson SAS.