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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 Neurokinin 3 Receptor Agonism Affect Hippocampal Neurogenesis in an Experimental Rat Model of Alzheimer's Disease?(Wiley, 2023) Koca, Raviye Ozen; Gormus, Z. Isik Solak; Solak, Hatice; Celik, Fatma Secer; 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 Reprograming cancer cells by a BODIPY G-quadruplex stabiliser(Royal Soc Chemistry, 2023) Baser, Aminesena; Basar, Beyza; Dogan, Hanim Beyza; Sener, Gulnur; Ozsamur, Nezahat Gokce; Celik, Fatma Secer; Altves, SafaaA cationic BODIPY-based G-quadruplex-selective stabiliser is developed and shown to decrease cancer cell migration-invasion up to 90%. The expression of critical genes (HIF1 alpha, VIM, CDH1) related to metastasis is modulated. The stabiliser reprograms hypoxia-adaptive metabolism and an 1.82-fold increase in O2 consumption, enabling back-to-normal switching of energy metabolism, is observed. Stabilisers with a strong G-quadruplex affinity (0.38 mu M Kd) significantly contribute to small molecule anti-cancer approaches. A BODIPY-based G-quadruplex-selective stabiliser is shown to silence regulator genes, reduce cell migration and invasion, and switch off the hypoxia-adaptive metabolism.Öğe Selection of Housekeeping Genes for Rat Hippocampus Expression Studies: Alzheimer's Disease Model(Karger, 2021) Celik, Fatma Secer; Koca, Raviye Ozen; Solak, Hatice; Gormus, Z. Isik Solak; Kutlu, Selim; Kurar, Ercan[Abstract Not Availabe]
