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, Yusuf
    The 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, Yusuf
    In 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
    Cytotoxic and Apoptotic Effects of Fisetin, Hesperetin and Vitexinon Acute Promyelocytic Leukemia Cells
    (Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Baran, Yusuf
    Acute 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: 49
    Citation - Scopus: 66
    Bioactive, 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, Ahmet
    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: 158-461mmolTrolox/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: 13
    Citation - Scopus: 13
    Stat 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, Güray
    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. © 2013 Elsevier Masson SAS.