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Öğe Apelin triggers macrophage polarization to M2 type in head and neck cancer(Elsevier Gmbh, 2023) Celik, Fatma Secer; Gunes, Canan Eroglu; Yavuz, Emine; Kurar, ErcanCancer comes after cardiovascular diseases in terms of mortality rate in the world. Chemotherapy, radiotherapy and surgical interventions are the current cancer treatment. Recently, it has been observed that immunothera-peutic approaches provide a significant improvement when used along with these interventions. The mono-nuclear system mainly consists of macrophages that play an active role in the pathology of many diseases because of having high plasticity capacities. Previous research suggested that they can be used as an alternative to cancer treatment. Aim was to investigate the effect of apelin on macrophage polarization in the tumor microenvironment.Mouse macrophage cell line RAW264.7 cells and head and were chosen for this study. The apelin expression was knockdown in neck cell carcinoma cell line SCCL MT1 cells using shRNA technique. SCCL MT1 cells having normal or suppressed apelin expression were co-cultured with mouse macrophage RAW264.7 cells. The effect of co-culturing on the expression of inflammatory genes in RAW264.7 cells was investigated.Suppressed apelin expression in SCCL MT1 cells resulted in elevated pro-inflammatory response in co-cultured macrophages. Expression of the IL113, IL6, and TNF alpha genes significantly increased, however anti-inflammatory cytokine levels were significantly decreased. However, in the control group, a downregulation was deter-mined in pro-inflammatory genes, while an increase was observed in anti-inflammatory genes. The protein levels of these cytokines in concordance with the RT-PCR analysis.As a result of this study, apelin released from cancer cells was found to affect macrophage polarization. These results indicated that the apelin peptide may cause the intense presence of M2-type macrophages in the tumor niche, and the therapeutic approaches targeting of apelin in cancer cells may have a potential role in macrophage polarization.Öğe Does Sertraline Affect Hypothalamic Food Intake Peptides in the Rat Experimental Model of Chronic Mild Stress-Induced Depression?(Springer/Plenum Publishers, 2022) Solak, Hatice; Gormus, Z. Isik Solak; Koca, Raviye Ozen; Gunes, Canan Eroglu; Kutlu, SelimDepression is a chronic, recurrent and life-threatening disease affecting approximately 15% of the world population. Depression is responsible for neuropathologies like decreased neurogenesis and increased dendritic atrophy. Antidepressant treatments increase hippocampal neurogenesis and neurotrophic factor expression. Based on this information, it was aimed to investigate effect of sertraline on depression in rats with chronic mild stress (CMS) model and to determine how it affects cell proliferation and hypothalamic peptide levels in hypothalamus. 56 adult male Wistar albino; control, depression(D), depression + sertraline, sertraline were divided into groups. Various stressors were applied to D for 30 days. Open field test (OFT) and forced swimming test (FST) were conducted to check whether the animals were depressed. On the 16th day osmotic minipump was placed subcutaneously and sertraline (10 mg/kg/day) was administered for 15 days. Behavior tests were done. Hypothalamic peptide gene expression levels were analyzed by quantitative RT-PCR. Statistical evaluations were made using ANOVA. It caused a decrease in the percentage of movement in the D and control groups in the OFT, an increase in the immobility time in the D group in the FST, and an increase in the swimming behavior in the DS group. Animals did not show any anxiological behavior based on the elevated plus maze test results. CMS caused a decrease in GLUT2 and NPY gene expression in the hypothalamus of animals, an increase in POMC and FGFR2, and an increase in IGFIR and GLUT2 gene expression in the DS group. Sertraline has been shown to ameliorate the effects of CMS-induced depression. Sertraline is thought to have a positive regulatory effect on both the formation of neural precursor cells and the survival of newly formed neurons in the hypothalamus. Newly formed neurons in the hypothalamus express food intake-related NPY, POMC, GLUT2 neurons, and thus hypothalamic tanycytes may play a key role in the control of energy metabolism.Öğe The Effect of Morphine Dependence and Morphine Withdrawal on Neuritin and Some Markers of Neurogenesis in the Rat Hippocampus(Wiley, 2023) Cimen, Yasin Ali; Yildiz, Ibrahim; Gunes, Canan Eroglu; Ozkurkculer, Alpaslan; Kurar, Ercan; Kutlu, Selim[Abstract Not Availabe]Öğe Effect of Naloxone Precipitated Morphine Withdrawal on Melatonin Receptor Expressions in Hippocampus and Hypothalamus Tissues in Morphine Dependent Rat(Karger, 2021) Cimen, Yasin Ali; Gunes, Canan Eroglu; Yildiz, Ibrahim; Ozdengul, Faik; Kurar, Ercan; Meral, Ismail; Kutlu, Selim[Abstract Not Availabe]Öğe Effects of Mu Opioidergic Receptors on Endoplasmic Reticulum Stress in the Hypothalamus on Rats(Wiley, 2023) Sen, Aysu; Gunes, Canan Eroglu; Caliskan, Zeynep; Erkaya, Zeliha; Dursun, Ebru Nur; Kurar, Ercan; Kutlu, Selim[Abstract Not Availabe]Öğe Glycoside oleandrin downregulates toll-like receptor pathway genes and associated miRNAs in human melanoma cells(Elsevier, 2022) Gunes, Canan Eroglu; Celik, Fatma Secer; Secme, Mucahit; Elmas, Levent; Dodurga, Yavuz; Kurar, ErcanMelanoma accounts for the majority of skin cancer-related deaths. Nerium oleander is a plant known to be toxic and consumed due to the cardiac glycosides it contains. Oleandrin is a cardiac glycoside obtained from of N. oleander. Beside capable of inhibiting proliferation and metastasis of cancer cells, cardiac glycoside derivative compounds cause cardiovascular side effects. Because of cardiovascular toxicity of clinically used cardiac gly-cosides, it is necessary to investigate cardiac glycoside derivative compounds capable of inhibiting proliferation and metastasis of cancer cells.It is known that oleandrin has anticarcinogenic effects in other cancers. Previous studies have shown that toll -like receptors (TLRs) and their related microRNAs (miRNAs) are associated with cancer. Therefore, aim was to investigate the effect of oleandrin on genes and miRNAs associated with TLRs in A375 melanoma cells in this study. The effects of oleandrin on cell viability, cytokines, apoptosis were evaluated using XTT, ELISA and TUNEL analyses, respectively. The effect of oleandrin on expression of TLR genes and 5 associated miRNAs in A375 cells has been determined by qRT-PCR. In addition, the levels of MyD88, TLR2 and TLR4 proteins were analyzed by western blot method.ELISA indicated that oleandrin treatment (47 nM at 48 h) reduced the level of proinflammatory cytokine IFNG. TUNEL analysis showed that apoptosis rate was significantly increased in the oleandrin dose group. According to qRT-PCR results, there was a significant decrease in IRAK1, IRAK4, MyD88, TLR2-TLR7 and TRAF3 expressions in the oleandrin treated group compared to the control (untreated cell). Also, a significant decrease in TLR4 protein expression has been observed. In addition, oleandrin significantly downregulated the levels of hsa-miRNA-146a-5p and hsa-miRNA-21-5p.In conclusion, it has been observed that oleandrin has an effect on TLR pathway-related genes and miRNAs in melanoma cells. We show that TLRs pathways and hsa-miR-146a-5p and hsa-miR-21-5p can participate in the oleandrin molecular mechanism of action.Öğe Hippocampal and Hypothalamic FBN1 Expression in an Experimental Opioid Addiction Rat Model(Karger, 2021) Gunes, Canan Eroglu; Cimen, Yasin Ali; Yildiz, Ibrahim; Kurar, Ercan; Kutlu, Selim[Abstract Not Availabe]Öğe Hypothalamic Expressions of Apelin, Apelin Receptor and Neuritine in the First Generation Rat Pups: A Maternal Depression Model(Karger, 2021) Kurar, Ercan; Gunes, Canan Eroglu; Koca, Raviye Ozen; Solak, Hatice; Koc, Aynur; Sahin, Zafer; Cuce, Gokhan[Abstract Not Availabe]Öğe Investigation of Some Nutrition-related Neuropeptide Expressions in Hypothalamus Tissues of Offspring Exposed to Maternal Depression and Sertraline Treatment.(Wiley, 2023) Solak, Hatice; Koca, Raviye Ozen; Gunes, Canan Eroglu; Uguz, Faruk; Ak, Mehmet; Sahin, Zafer; Kurar, Ercan[Abstract Not Availabe]Öğe Knockdown of lncRNA HIF1A-AS2 increases drug sensitivity of SCLC cells in association with autophagy(Humana Press Inc, 2021) Guclu, Ebru; Gunes, Canan Eroglu; Kurar, Ercan; Vural, HasibeThe aim of this study was to determine the effect of lncRNA HIF1A-AS2 on autophagy-associated drug resistance in small cell lung cancer (SCLC) cells. The expression of HIF1A-AS2 was silenced by siRNA in doxorubicin-sensitive H69 and doxorubicin-resistant H69AR cells. Then, cytotoxicity, apoptosis and autophagy analyses were carried out in the normoxic and CoCl2-induced hypoxic environment. The effect of HIF1A-AS2 on the expression levels of genes, which are associated with drug resistance and autophagy, was determinated by qRT-PCR analysis. The levels of MRP1, HIF-1 alpha and Beclin-1 were analyzed by western blot method. Knockdown of HIF1A-AS2 increased doxorubicin sensitivity of SCLC cells and decreased autophagy. Knockdown of HIF1A-AS2 has also affected the expression of several genes that will increase drug sensitivity and inhibit autophagy in both cell lines. The levels of HIF-1 alpha and Beclin-1 were decreased in both cell lines by knockdown of HIF1A-AS2. MRP1 expression was decrease in H69AR cells. In addition, CoCl2-induced hypoxic environment decreased in doxorubicin sensitivity of H69 cells, and knockdown of HIF1A-AS2 reversed this effect of hypoxia. Knockdown of HIF1A-AS2 increased drug sensitivity of SCLC cells in relation to autophagy. Therefore, hypoxia-HIF1A-AS2-autophagy interaction is thought to be determinative in drug sensitivity of these cells.Öğe Knockdown of lncRNA ZEB2NAT suppresses epithelial mesenchymal transition, metastasis and proliferation in breast cancer cells(Elsevier, 2021) Gunes, Canan Eroglu; Guclu, Ebru; Vural, Hasibe; Kurar, ErcanBreast cancer is the second most common cause of cancer-related mortality in women. Breast cancer metastasis which usually is observed at the last stage is the major cause of breast cancer-related death. Long non-coding RNAs (lncRNAs) are member of the non-coding RNA family. It is known that lncRNAs have important functions in the genes regulation of different processes and pathways such as EMT (Epithelial mesenchymal transition), metastasis and apoptosis. Therefore, it is inevitable that lncRNAs have potential contribution for the understanding of cancer pathogenesis. lncRNA-ZEB2NAT is the natural antisense transcript of ZEB2. Herein, we investigated the effects of lncRNA-ZEB2NAT on process of EMT, metastasis and apoptosis in MCF7 and MDA-MB231 breast cancer cells. The effect of ZEB2NAT on the expression of important genes in EMT, metastasis and apoptosis, and some protein levels was determined by qRT-PCR and western blot analysis, respectively. The effects of ZEB2NAT on cell proliferation, apoptosis, invasion and colony formation were evaluated using XTT, annexin V, invasion and colony assays, respectively. The ZEB2NAT knockdown caused anti-metastatic and apoptotic effects. The ZEB2NAT knockdown resulted in a decrease in ZEB2 and N-cadherin but an increase in E-cadherin protein levels. In addition, it was determined that ZEB2NAT knockdown significantly decreased cell proliferation and stimulated apoptosis in both cells. It was found that ZEB2NAT knockdown significantly decreased invasion and colony formation in both cells. ZEB2NAT knockdown showed anti-metastatic and apoptotic effect by affecting the important genes in both cells. These results have suggested that ZEB2NAT has an important role in EMT, metastasis and apoptosis in breast cancer and ZEB2NAT knockdown caused significant anti-cancer activities.Öğe Synthesis and evaluation of anticancer effect of a novel molecule based-on pillar[5]arene including multi quinoline units(Springer Birkhauser, 2020) Gunes, Canan Eroglu; Karaselek, Mehmet Ali; Kursunlu, Ahmed Nuri; Ozmen, Mustafa; Kurar, ErcanIn this study, pillar[5]arene containing ten terminal alkynyl-functional group was prepared and carried out an optimization procedure for target molecule with using 5-hydroxyquinoline molecule known with biological activity. The novel molecule was named as iso-QP[5] and characterized by FT-IR, melting point, NMR, elemental analysis, and mass spectroscopy. The aim was to evaluate the anticancer effects of iso-QP[5] on MCF7 human breast cancer cells. The IC50 dose of iso-QP[5] in MCF7 cells was found to be 25 mu M for 24 h using XTT assay. Expressions of eight genes for apoptosis were determined by qPCR. The results showed a significant increase in the expression of BAX, CASP3, CASP9, CYCS, and P53 genes after treatment with iso-QP[5] in MCF7 cells. However, iso-QP[5] treatment significantly decreased expression of BCL2 and CASP8 genes. It is concluded that novel molecule iso-QP[5] caused apoptosis by regulating genes that are important in apoptosis in human breast cancer cells.