Browsing by Author "Ozkan-Yilmaz, Ferbal"

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Artesunate Inhibits Melanoma Progression in Vitro Via Suppressing Stat3 Signaling Pathway
(Springer Heidelberg, 2021) Berkoz, Mehmet; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Krosniak, Miroslaw; Turkmen, Omer; Korkmaz, Duygu; Keskin, Siddik
Background Melanoma is a life-threatening cancer characterized with a potentially metastatic tumor of melanocytic origin. Improved methods or novel therapies are urgently needed to eliminate the development of metastases. Artesunate is a semi-synthetic derivative of artemisinin used for trarment of malaria and cancer. The purpose of this study was to investigate the anti-cancer effect of artesunate and the role on STAT3 signaling in A375 human melanoma cell line. Methods Melanoma cells were treated with artesunate at concentrations of 0-5 mu M for 24 and 48 h. The inhibition of cell viability, colony formation, migration, invasion, adhesion, percentage of apoptotic cells, and expressions of signal transducer and activator of transcription-3 (STAT3) and related proteins were examined. Results Artesunate inhibited cellular proliferation of cancer cells by induction of apoptosis at sub-toxic doses. Cells treated with artesunate showed an inhibition in adhesion to extracellular matrix substrate matrigel and type IV collagen. Artesunate treatment showed a decreased cellular migration, invasion, and colony formation in melanoma cells. Artesunate also inhibited STAT3 and Src activations and STAT3 related protein expressions; such as metalloproteinase 2 (MMP-2), MMP-9, Mcl-1, Bxl-xL, vascular endothelial growth factor (VEGF), and Twist. Moreover, overexpression of constitutively active STAT3 in A375 cells attenuated the anti-proliferative, apoptotic and anti-invasive effects of artesunate. Conclusion The results obtained from this study demonstrated that the anticancer activity of artesunate occurred via STAT3 pathway and its target proteins. Therefore, it can be suggested that artesunate may be an important candidate molecule in the treatment of melanoma.
Effects of Dietary Nucleotide Yeast on Immune Responses and Antioxidant Enzyme Activities of Rainbow Trout Juveniles (Oncorhynchus Mykiss)
(Israeli Journal of Aquaculture-bamidgeh, 2016) Ozluer-Hunt, Arzu; Ozkan-Yilmaz, Ferbal; Berkoz, Mehmet; Engin, Kenan; Gunduz, Suna Gul; Yalin, Serap
This study aimed at demonstrating the effects of dietary supplementation of nucleotide yeast base protein (Nu-Pro (R)) (NP) on the antioxidant enzyme activities and immune response in liver and blood tissues of rainbow trout (Oncorhynchus mykiss). Fish with an average initial weight of 27.75 +/- 0.26 g were randomly assigned to four groups with three replicates. Throughout the 60 day grow-out period the control group was fed a fish meal based basal diet, and three other groups were fed diets in which 20 (NP 20), 40 (NP 40) and 60 % (NP 60) fish meal was substituted with nucleotide (Nu-Pro (NP) yeast). There were no significant changes of superoxide dismutase (SOD) and catalase (CAT) activities in liver among the experimental groups. A significant decrease (P<0.05) in malondialdehyde (MDA) level of tissue was observed in all nucleotide supplemented groups when compared to the control group. Serum lysozyme (LYZ) and myeloperoxidase (MPO) activities and nitric oxide (NO) level of liver tissue were significantly (P<0.05) increased in fish fed with nucleotide yeast based protein diets. The results showed that the fish in all nucleotide supplemented groups showed significantly better antioxidant activity and immune responses.
Effects of Dietary Selenium of Organic Form Against Lead Toxicity on the Antioxidant System in Cyprinus Carpio
(Springer, 2014) Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Gunduz, Suna Gul; Berkoz, Mehmet; Yalin, Serap
In this study was evaluated potential protective effect of organic selenium (Se) on heavy metal stress induced by lead (Pb) in Cyprinus carpio. For this reason, C. carpio was exposed to sublethal concentration of Pb (1.5 mg/L Pb(NO3)(2)) for 14 days. The fish were fed a basal (control; measured 0.55 mg/kg Se) diet or a basal diet supplemented with 2.50 mg/kg (measured 2.92 mg/kg Se) organic Se (Sel-Plex(A (R))) during the experiment period. The variations in glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) activities, and levels of reduced glutathione (GSH) with malondialdehyde (MDA) in liver and brain tissues of C. carpio were investigated in experimental groups. GSH levels in liver and brain tissues were significantly decreased by exposure to Pb. GST activity was significantly increased (p < 0.05) in liver tissue, but decreased in brain of treated fish by exposure to Pb. Also, GSH-Px activity was significantly increased in liver tissue, but decreased in brain of Pb-treated fish. Levels of MDA were increased in liver and brain of Pb-treated fish. The organic Se treatment for Pb-intoxicated animals improved activities of GSH-Px, GST and levels of MDA within normal limits. Supplemented Se could be able to improve Pb-induced oxidative stress by decreasing lipid peroxidation and regulating antioxidant defense system in tissues.
Effects of Fenbutatin Oxide on Antioxidant System of Different Tissues in Cyprinus Carpio (L., 1758)
(Parlar Scientific Publications (p S P), 2017) Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Gunduz, Suna Gul; Berkoz, Mehmet; Yalin, Serap; Yildirim, Metin
In this study, effects of sublethal concentrations of fenbutatin oxide on catalase (CAT) and superoxide dismutase (SOD) activities and lipid peroxidation in muscle, liver, kidney and brain tissues of Cyprinus carpio were investigated. The 96-hours LC50 value for fenbutatin oxide was determined as 1.544 mg/L for C. carpio in this study. 0.15 mg/L (1/10 of LC50) and 0.30 mg/L (1/5 of LC50) sublethal concentrations were applied for 96 h (4 days) in this experiment. The CAT activities in tissues were increased relation to doses applied. The SOD activities were decreased by 0.30 mg/L. The tissue MDA levels were significantly increased in relation to dose applied.
Effects of Methidathion on Antioxidant System and Expression of Heat Shock Protein 70 (Hsp70) Gene in the Liver of Oreochromis Niloticus L. 1758
(Parlar Scientific Publications (p S P), 2015) Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Gunduz, Suna Gul; Berkoz, Mehmet; Yalin, Serap; Sahin, Nefise Ozler
In this study, effects of sublethal concentrations of methidathion on catalase (CAT), superoxide dismutase (SOD), glutathion peroxidase (GSH-Px) activities and lipid peroxidation with expression of heat shock protein (HSP70) gene in liver tissues of Oreochromis niloticus were investigated. The 96-h LC50 value for methidathion was determined as 0.1045 mg/L for O. niloticus in this study. 0.013 (1/8 of LC50) and 0.026 mg/L (1/4 of LC50) sublethal concentrations were applied for 4 and 10 days in this experiment. CAT and GSH-Px activities in liver tissue were increased, in relation to both the time and doses applied. SOD activities were increased under the influence of both concentrations at the 4th day, but on 10th day, it was decreased with influence of 0.026 mg/L methidathion concentration. The tissue MDA levels were significantly increased in relation to both the time and dose applied. The relative mRNA levels of the HSP70 gene were detected by real time polymerase chain reaction (RT-PCR). The mRNA levels of HSP70 gene by methidathion increased significantly on 4th days compared to control, but decreased significantly on 10th days.
Influence of Sublethal Chlorpyrifos Exposure on Oxidative Stress and Acetylcholinesterase Activity in Common Carp (Cyprinus Carpio)
(Parlar Scientific Publications (p S P), 2019) Berkoz, Mehmet; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Gunduz, Suna Gul; Yildirim, Metin; Yalin, Serap
The commonly used pesticides in agriculture cause enzyme inactivation and DNA damage via reacting with macromolecules and may also initiate peroxidation of poly-unsaturated fatty acids (PUFA) by generating of the reactive oxygen species (ROS), as a consequence they can lead to the oxidative stress. The objective of this study was to determine the oxidative and neurotoxic potential of sublethal chlorpyrifos in the brain tissue of Cyprinus carpio (C. carpio) for a period of 96 and 240 hours, respectively. Therefore, the levels of malondialdehyde (MDA), glutathione (GSH), advanced oxidation protein products (AOPP), protein carbonyl, and 8-hydroxydeoxyguanosine (8-OHdG) levels and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and acetylcholinesterase (AChE) were investigated in order to determine the neurotoxic effect in brain tissue of C. carpio exposed to chlorpyrifos. Administration of chlorpyrifos at 0.26 and 0.52 mg/L concentrations caused a significant increase in MDA levels at the 240th hour (p<0.05), the latter concentration increased the GSH level but decreased SOD, GSH-Px, and CAT activities at the 240th hour (p<0.05). Only 0.52 mg/L of chlorpyrifos administration increased protein carbonyl but not AOPP levels at the 240th hour (p<0.05). 0.26 and 0.52 mg/L of chlorpyrifos concentrations caused a significant increase 8-OHdG levels at the 96th and the 240th hours (p<0.05). Chlorpyrifos statistically significantly reduced the AChE levels in both periods and at all administered concentrations (p<0.05). We observed an enhanced oxidative stress and inhibited AChE activity in the brain tissue of C. carpio after exposure to chlorpyrifos. These findings show that sublethal concentration of chloropyrifos leads to significant toxicity in the brain tissues of C. carpio.
Prophylactic Effect of Biochanin a in Lipopolysaccharide-Stimulated Bv2 Microglial Cells
(Taylor & Francis Ltd, 2020) Berkoz, Mehmet; Krosniak, Miroslaw; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu
Aim/Purpose of the study:Inhibition of microglial activation using phytochemicals may be a potential candidate for the prevention of neurodegenerative diseases caused by neuroinflammation and oxidative stress. The goal of this study was to investigate the protective role of Biochanin A on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. BV2 microglial cells were treated with LPS in the presence and absence of Biochanin A.Materials and methods:For this aim, nitric oxide production, nuclear factor kappa B (NF-kappa B), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, Prostaglandin E2 (PGE2), and reactive oxygen species (ROS) levels, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), myeloid differentiation factor-88 (MyD88), and toll like receptor-4 (TLR-4) protein expressions, Akt and ERK1/2 phosphorylation levels were measured.Results:Biochanin A pretreatment resulted in significant and concentration-dependently reduced the LPS-induced production of nitric oxide, NF-kappa B p65, TNF-alpha, IL-1 beta, IL-6, PGE2, and ROS compared to the untreated group. Biochanin A prophylaxis exerted an anti-inflammatory effect by suppressing iNOS, COX-2, MyD88, and TLR-4 protein expressions and Akt and ERK1/2 pathway activation.Conclusion:Taken together, these results show that Biochanin A exerts antioxidant and anti-inflammatory activities, thus may be beneficial for preventing neurodegenerative diseases mediated by microglial cells.
Prophylactic Effect of Myricetin and Apigenin Against Lipopolysaccharide-Induced Acute Liver Injury
(Springer, 2021) Berkoz, Mehmet; Unal, Seda; Karayakar, Fahri; Yunusoglu, Oruc; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Aslan, Ali
Background Liver has an important role in the initiation and progression of multiple organ failure that occurs in sepsis. Many natural active substances can be used to reduce the liver injury caused by sepsis. For this aim, the effects of myricetin and apigenin on mice model of acute liver injury was evaluated in this study. Methods and results Thirty-six mice were randomly divided into six groups as; control, lipopolysaccharide (LPS) (5 mg/kg), LPS + myricetin (100 mg/kg), LPS + myricetin (200 mg/kg), LPS + apigenin (100 mg/kg), and LPS + apigenin (200 mg/kg) groups. Myricetin and apigenin were administered orally for 7 days, and LPS was administered intraperitoneally only on the 7th day of the study. 24 h after LPS application, all animals were sacrificed and serum biochemical parameters, histopathology and oxidative stress and inflammation markers of liver tissue were examined. Myricetin and apigenin pre-treatments increased serum albumin and total protein levels, liver GSH level and catalase and SOD activities and decreased serum ALT, AST, ALP, gamma-GT, CRP, total and direct bilirubin levels, liver MPO activity, MDA, NOx, PGE(2), TNF-alpha, IL-1 beta, and IL-6 levels, iNOS and COX-2 mRNA levels, phosphorylation of NF-kappa B p65, I kappa B, and IKK proteins but not p38, ERK, and JNK proteins in LPS-treated mice. Myricetin and apigenin administration also regained the hepatic architecture disrupted during LPS application. Conclusion Myricetin and apigenin pre-treatments led to reduction of liver injury indices and oxidative stress and inflammatory events and these flavonoids has probably hepatoprotective effects in acute liver injury.
Protective Effect of Myricetin, Apigenin, and Hesperidin Pretreatments on Cyclophosphamide-Induced Immunosuppression
(Taylor & Francis Ltd, 2021) Berkoz, Mehmet; Yalin, Serap; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Krosniak, Miroslaw; Francik, Renata; Yildirim, Metin
Aim: Major side effects of cyclophosphamide administration are immunosuppression and myelosuppression. The immunomodulatory effects of plant bioactive compounds on chemotherapy drug-induced immunosuppression may have significant effects in cancer treatment. For this reason, we investigated the immunomodulatory effect of myricetin, apigenin, and hesperidin in cyclophosphamide-induced immunosuppression in rats. Methods: In our study, a total of 64 rats were used, and divided into eight equal groups. These groups were: control, cyclophosphamide, cyclophosphamide+myricetin (100mg/kg), cyclophosphamide+myricetin (200mg/kg), cyclophosphamide+apigenin (100mg/kg), cyclophosphamide+apigenin (200mg/kg), cyclophosphamide+hesperidin (100mg/kg), and cyclophosphamide+hesperidin (200mg/kg). Myricetin, apigenin, and hesperidin pretreatments were performed for 14d, while cyclophosphamide application (200mg/kg) was performed only on the 4th day of the study. Levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, and natural killer cell cytotoxicity were determined. In addition, we measured pro-inflammatory cytokines, and followed lipid peroxidation and antioxidant markers and examined the histology of bone marrow, liver and spleen in all groups. Results: During cyclophosphamide treatment, all three phytochemicals increased the levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, antioxidant markers, and natural killer cell cytotoxicity. Moreover, the agents decreased the levels of pro-inflammatory cytokines and mediators, reduced lipid peroxidation markers, and reduced tissue damage in liver, spleen, and bone marrow. Conclusion: Our study demonstrated that myricetin, apigenin, and hesperidin can reduce the immunosuppressive effect of cyclophosphamide by enhancing both innate and adaptive immune responses, and these compounds may be useful immunomodulatory agents during cancer chemotherapy.
Roe Protein Hydrolysate of Alburnus Tarichi Induces Apoptosis in Breast Cancer Mcf-7 and Mda-Mb Cells Through a Caspase-Dependent Pathway
(General Physiol and Biophysics, 2020) Berkoz, Mehmet; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Krosniak, Miroslaw; Turkmen, Omer; Yunusoglu, Oruc
The protein hydrolysates of fishes have been reported to be a potential source of many health benefits components for pharmaceutical or nutritional applications. The aim of this study is to examine the possible antiproliferative function of roe protein hydrolysates of Alburnus tarichi using enzymatic hydrolysis against breast cancer cells and explore its detailed mechanisms. In addition, we evaluated the effects of protein hydrolysate on the proliferation and apoptosis of two human breast cancer cell lines (MCF-7 and MDA-MB-231). The cultured cells were treated with protein hydrolysate at concentrations of 0-5 mu g/ml for 24 h and 48 h. Inhibition of cell proliferation, percentage of apoptotic cells, cell cycle distribution, morphological changes, DNA fragmentation, intracellular reactive oxygen species (ROS) production, and apoptotic protein levels were also examined. Decreases in proliferation of MCF-7 and MDA-MB-231 cells were observed after treatment with the protein hydrolysate in a dose-dependent manner. Distinct morphological changes, a typical pattern of fragmented DNA, and increased intracellular ROS production and apoptotic protein levels were observed in both cell lines after hydrolysate treatment (p < 0.05). The results suggested that the protein hydrolysate inhibits the proliferation of human breast cancer cell lines by introducing apoptosis through a caspase-dependent pathway in a dose-dependent manner.
Rosa Canina L. Ethanolic Extract Induces the Anti-Proliferative and Apoptosis Potential in Mcf-7 and Mda-Mb Cell Lines
(Parlar Scientific Publications (p S P), 2019) Berkoz, Mehmet; Ozkan-Yilmaz, Ferbal; Ozluer-Hunt, Arzu; Yildirim, Metin; Allahverdiyev, Oruc; Aslan, Ali
Rosa canina L. (rose hip) fruits have been used for their diuretic, laxative, anti-gout, anti rheumatism properties in traditional medicine. Rose hip berries contain a variety of components such as flavonoid. The previous studies showed that flavonoid has anti-cancer properties. Tha aim of this study is to evaluate and screen the effect of apoptosis and the anticancer potential of rose hip ethanolic extract on human breast cancer cell lines; MCF-7 and MDA-MB-468. The anti-proliferative activity of rose hip extract was evaluated using MTT, flowcytometry by annexin V/PI double staining, and caspase-3 activity. The results of MTT showed that the EDso of both human breast cancer cell lines was 25 g/mL of rose hip extract, 48 hours after treatment. Flowcytometry by annexin V/PI showed that rose hip extract induced late apoptosis in MCF7 and early apoptosis in MDA-MB-468. In addition, the caspase-3 colorimetric method showed that caspase-3 increased in the MDA-MB-468 after treatment with rose hip extract. As a result, the ethanol of rose hip ethanolic extract induced apoptosis in both human breast carcinoma cell lines.