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Öğe A review on melatonin’s effects in cancer: Potential mechanisms(Bentham Science Publishers B.V., 2018) Hanikoğlu, Ayşegül; Küçüksayan, Ertan; Akduman, Rana; Özben, TomrisThis systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth. © 2018 Bentham Science Publishers.Öğe A social attention with altmetric score analysis on the relationship between oxidative stress and cancer(2022) Hanikoğlu, Ferhat; Vardar, Gökay; Özben, Tomris; Karadağ, Mehmet; Dokur, MehmetOxidative stress has a crucial role in the development of various cancers. The aim of our study was to identify and analyze research articles about oxidative stress and cancer that have attracted the highest online attention. Our study is the first one evaluating social media attention to the articles on cancer and oxidative stress published in academic literature. Altmetric Explorer was used to identify research articles about oxidative stress and cancer. We evaluated the top 50 research articles having the highest Altmetric attention scores (AAS), using the Altmetric.com database. The Altmetric Attention Score (AAS) of 50 articles (T50) investigated was between 15 and 445 (mean±SD; 60.66±86.18). The social media platforms where the T50 articles are mentioned from highest to the lowest scores are the Facebook (n=2678) followed by Twitter (n=886) and Google + users (n=214). According to demographic breakdowns in Twitter, tweet counts were similar between scientists (34%) and not scientists (32%). Total citations of the 50 articles ranged from 3 to 3700 (mean ± SE; 203.40±87.07). A weak statistically significant positive correlation was found between the Altmetric score and the Q category (r=0.338: p=0.016). Interestingly, there was no correlation between Altmetric score and number of article citations. The increasing use of online social media platforms makes this area worthy, and the online impact of an article is becoming progressively more convenient for academic and public accessibility. Social media also may give oppurtunity to the researchers for disseminating their studies in scholar and non-scholar platforms.Öğe Effects of somatostatin and vitamin C on the fatty acid profile of breast cancer cell membranes(Bentham Science Publ Ltd, 2019) Hanikoğlu, Ayşegüll; Küçüksayan, Ertan; Hanikoğlu, Ferhat; Özben, Tomris; Menounou, Georgia; Sansone, Anna; Ferreri, CarlaBackground: Vitamin C (Vit C) is an important physiological antioxidant with growing applications in cancer. Somatostatin (SST) is a natural peptide with growth inhibitory effect in several mammary cancer models. Objective: The combined effects of SST and Vit C supplementation have never been studied in breast cancer cells so far. Methods: We used MCF-7 and MDA-MB231 breast cancer cells incubated with SST for 24h, in the absence and presence of Vit C, at their EC 50 concentrations, to evaluate membrane fatty acid-profiles together with the follow-up of EGFR and MAPK signaling pathways. Results: The two cell lines gave different membrane reorganization: in MCF-7 cells, decrease of omega-6 linoleic acid and increase of omega-3 fatty acids (Fas) occurred after SST and SST+Vit C incubations, the latter also showing significant increases in MUFA, docosapentaenoic acid and mono-trans arachidonic acid levels. In MDA-MB231 cells, SST+Vit C incubation induced significant membrane remodeling with an increase of stearic acid and mono-trans-linoleic acid isomer, diminution of omega-6 linoleic, arachidonic acid and omega-3 (docosapentaenoic and docosadienoic acids). Distinct signaling pathways in these cell lines were studied: in MCF-7 cells, incubations with SST and Vit C, alone or in combination significantly decreased EGFR and MAPK signaling, whereas in MDA-MB231 cells, SST and Vit C incubations, alone or combined, decreased pP44/42 MAPK levels, and increased EGFR levels. Conclusion: Our results showed that SST and Vit C can be combined to induce membrane fatty acid changes, including lipid isomerization through a specific free radical-driven process, influencing signaling pathways.Öğe Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes(Canadian Science Publishing, 2020) Hanikoğlu, Ayşegül; Küçüksayan, Ertan; Hanikoğlu, Ferhat; Özben, Tomris; Menounou, Georgia; Sansone, Anna; Ferreri, CarlaBreast cancer is a worldwide commonly found malignancy in women and effective treatment is regarded as a huge clinical challenge even in the presence of several treatment options. Extensive literature is available demonstrating polyphenols as phytopharmaceutical anticancer agents. Among the polyphenols, quercetin and curcumin have been reported to have a strong potential against breast cancer. However, so far, no comprehensive study has been performed to demonstrate the anticarcinogenic effects of curcumin, quercetin, and their combinations with somatostatin on the fatty acid profile of breast cancer cell membranes. We used MCF-7 and MDA-MB231 breast cancer cells incubated with curcumin and quercetin for 24 h, in the absence and presence of somatostatin, at their EC50 concentrations to evaluate membrane fatty acid based functional lipidomics together with the followup of EGFR and MAPK signaling pathways. The two cell lines gave different membrane free fatty acid reorganization. In MCF-7 cells, the following changes were observed: an increase of omega 6 linoleic acid in the cells incubated with somatostatin + quercetin and quercetin and a decrease of omega 3 acids in the cells incubated with somatostatin + curcumin compared to somatostatin and significant increases of monounsaturated fatty acid (MUFA), mono-trans arachidonic acid levels and docosapentaenoic acid for the cells incubated with somatostatin + quercetin compared to the control cells. In MDA-MB231 cells, incubations with curcumin, quercetin, and somatostatin + quercetin induced the most significant membrane remodeling with the increase of stearic acid, diminution of omega 6 linoleic, arachidonic acids, and omega 3 (docosapentaenoic and docosahexaenoic acids). Distinct signaling pathway changes were found for these cell lines. In MCF-7 cells, separate or combined incubations with somatostatin and quercetin, significantly decreased EGFR and incubation with curcumin decreased MAPK signaling. In MDA-MB231 cells, incubation with curcumin decreased AKT1 and p-AKT1 (Thr308) levels. Incubation with curcumin and quercetin decreased the EGFR levels. Our results showed that cytostatic and antioxidant treatments can be combined to induce membrane fatty acid changes, including lipid isomerization as specific free radical driven process, and to influence signaling pathways. This study aimed to contribute to the literature on these antioxidants in the treatment of breast cancer to clarify the effects and mechanisms in combination with somatostatin.Öğe Plasma thiol/disulphide homeostasis changes in patients with relapsing-remitting multiple sclerosis(2021) Özben, Serkan; Küçüksayan, Ertan; Köseoğlu, Mesrure; Erel, Özcan; Neşelioğlu, Salim; Özben, TomrisBackground: Multiple sclerosis (MS) is a neuroinflammatory disease and inflammation and oxidative stress play important roles in its pathology. Thiol/disulphide homeostasis (TDH) is a special oxidative stress biomarker that has been found to be affected in several disorders including MS. There is no study demonstrating the effects of attack status of the relapsing-remitting multiple sclerosis (RRMS) patients on TDH levels. Our aim was to determine TDH levels in three different periods of RRMS patients and healthy individuals. Methods: The study was carried out in 29 patients with RRMS without a prior attack in the last twelve months (MS Control), 21 RRMS patients having a clinical acute attack within the last week (MS relapse), 12 of 21 MS relapse patients one month after the onset of attack and following 1000 mg methylprednisolone for 7 days (MS Remission) and 30 age- and sex-matched healthy individuals. TDH status was determined using an automated spectrophotometric analysis method. TDH levels in all patient groups and control subjects were compared with each other. Results: The lowest native thiol, total thiol levels and native thiol/total thiol ratio were found in the MS relapse patients in comparison to the MS control, MS remission groups and healthy controls. In contrast, disulphide levels, disulphide/native thiol and disulphide/total thiol ratios were highest in the MS relapse group compared to the other patient groups and healthy subjects. Conclusion: Our findings indicate that increased oxidative stress in RRMS patients is reflected with decreased native and total thiol and increased disulphide levels. Since the formation of disulphide bonds is reversible, the progression of RRMS involving abnormal TDH may be controlled, converting disulphides to thiols. So, we suggest determining the dynamic TDH status as a novel and special biomarker in the diagnosis and prognosis of the RRMS patients. What’s known • Multiple sclerosis (MS) is a neuroinflammatory disease and inflammation and oxidative stress play important roles in its pathology. • Like other inflammatory diseases, oxidative stress is associated with MS playing an important role in the pathogenesis of MS. What’s new • Our study provides original data on dynamic Thiol/disulphide homeostasis (TDH) status in the relapsing-remitting multiple sclerosis (RRMS) patients at three different periods of the disease and examines whether plasma TDH can be used as a special oxidative stress biomarker in the diagnosis and follow-up of the RRMS patients and their response to the therapyÖğe Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines(2022) Küçüksayan, Ertan; Sansone, Anna; Chatgilialoglu, Chryssostomos; Özben, Tomris; Tekeli, Demet; Talibova, Günel; Ferreri, CarlaAbstract: The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell lines of the same cancer type. We used 50 µM sapienic acid supplementation, a non-toxic concentration, to cultivate MCF-7 and 2 triplenegative breast cancer cells (TNBC), MDA-MB-231 and BT-20. We followed up for three hours regarding membrane fatty acid remodeling by fatty acid-based membrane lipidome analysis and expression/phosphorylation of EGFR (epithelial growth factor receptor), mTOR (mammalian target of rapamycin) and AKT (protein kinase B) by Western blotting as an oncogenic signaling cascade. Results evidenced consistent differences among the three cell lines in the metabolism of n-10 fatty acids and signaling. Here, a new scenario is proposed for the role of sapienic acid: one based on changes in membrane composition and properties, and the other based on changes in expression/activation of growth factors and signaling cascades. This knowledge can indicate additional players and synergies in breast cancer cell metabolism, inspiring translational applications of tailored membrane lipid strategies to assist pharmacological interventions.
