Browsing by Author "Pehlivanoglu, Suray"

Now showing 1 - 2 of 2

Identification of Novel Mutations of Insulin Receptor Substrate 1 (Irs1) in Tumor Samples of Non-Small Cell Lung Cancer (Nsclc): Implications for Aberrant Insulin Signaling in Development of Cancer
(Soc Brasil Genetica, 2019) Gorgisen, Gokhan; Hapil, Fatma Zehra; Yilmaz, Ozlem; Cetin, Zafer; Pehlivanoglu, Suray; Ozbudak, Irem Hicran; Ozes, Osman Nidai
Lung cancer is the leading cause of cancer-related death, and NSCLC constitutes nearly 85%-90% of all cases. The IRS proteins function as adaptors and transmit signals from multiple receptors. Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. Therefore, we thought that gain of function mutantions of IRS1 could be related to development of lung cancer. In line with this, we wanted determine whether the IRS1 gene was mutated in the coding regions surrounding YXXM motifs. We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. We generated IRS1 expression vectors harboring p.S668T, p.D674H and double mutants. Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. Also, our mutants induced proliferation, glucose uptake, inhibited the migration of 293T cells and affected the responsiveness of the cells to cisplatin and radiation. Our results suggest that these novel mutations play a role in the phenotype of lung cancer.
Synthesis of Carbazole-Substituted Thiosemicarbazone and Its Cu(Ii) Complex, Dna/Protein Binding, Cytotoxic, Antiproliferative Activities and Molecular Docking Studies
(Elsevier, 2023) Findik, Mukerrem; Kuzu, Burak; Pehlivanoglu, Suray; Kaya, Serdal; Sayin, Ulku; Akgemci, Emine Guler; Saf, Ahmet Ozgur
In this study, 9-ethyl-3-carbazolecarboxaldehyde-4-ethyl-thiosemicarbazone (ECCAET) and its copper(II) com-plex (Cu(ECCAET)2) were firstly synthesized and characterized. DFT and EPR studies confirmed that the complex is mononuclear and has square planar geometry. The interaction of all synthesized compounds with calf thymus DNA (CT-DNA) was examined by absorption and fluorescent spectroscopy. The experimental results showed that Cu(ECCAET)2 interacts with DNA via an intercalative binding mode. The binding interactions of the complex with CT-DNA have been confirmed through viscosity measurements revealing that the complex interacts with DNA via intercalation. Furthermore, the protein binding ability of ECCAET and Cu(ECCAET)2 was investigated using BSA via electronic absorption spectral titration, fluorescence quenching, and synchronous fluorescence spectrum studies, which revealed that the Cu(ECCAET)2 strongly bound to BSA over the ligand. Molecular docking studies were also performed to support the bonding mechanism of ECCAET and Cu(ECCAET)2 with DNA and BSA. The biological activity studies of ECCAET and Cu(ECCAET)2 against cancer cells were also investigated. A panel of cancer cell lines, including A2780 human ovarian adenocarcinoma, MDA-MB-231 human triple-negative breast adenocarcinoma, and as a control non-cancerous L929 fibroblast cell lines were also used to test the compounds' anticancer activities. Cytotoxic and antiproliferative properties of Cu(ECCAET)2 were visibly higher than its ligand (ECCAET) for all tested cell lines. The Cu(ECCAET)2 had a distinctive biological effects on A2780, and MDA-MB-231 cells compared to non-cancerous cells. Within these results, Cu(ECCAET)2 was found a promising drug candidate against gynecologic cancer diseases.