Şener, A. | Çevik, Ö. | Özsavci, D. | Yanikkaya-Demirel, G.

Article | 2011 | Marmara Pharmaceutical Journal15 ( 1 ) , pp.30 - 37

Gamma-glutamyltransferase (GGT), a plasma membran enzyme, plays important role in the reduced glutathione (GSH) metabolism. GGT activity during the catabolism of GSH originates the thiol dipeptide cysteinylglycine, whose-SH group is provided in particular with a much stronger iron-reducing ability. Recent research indicates that increased serum GGT activity could be used as a marker for increased oxidative stress in human. GGT activity is also found in platelets. Redox reactions can modify platelet functions. However, the role of platelet-GGT activity on its redox enviroment is unknown. The objective of the present work is to determ . . .ine whether the platelet-bound GGT activity initiates oxidative modifications and apoptotic stimuli in presence of iron(III). In our study, lipid peroxidation, protein oxidation, GSH, phosphatidylserine (PS) and caspase-3 levels of platelets were investigated after inhibiting platelet GGT activity with inhibitors and/or stimulating platelet GGT activity with its substrates in the presence of iron(III). The resulting data showed significantly higher levels of lipid peroxidation and protein oxidation in the GGT activity-stimulated platelets in comparison with the GGT activity inhibited platelets in the presence of iron(III). GSH contents of the GGT activity-stimulated platelets were significantly reduced. No significant difference was observed caspase-3 activities of platelets. However, PS externalization in GGT activity stimulated platelets were increased compared to the GGT activityinhibited platelets in the early stage apoptosis/activation. Platelet-GGT/GSH/iron(III) system can induce oxidative modifications and PS externalization on human platelets. Thus, platelet bound-GGT may contribute to the increase of reactive oxygen species (ROS) in its enviroment and promote cardiovascular diseases Daha fazlası Daha az

Kalay, S. | Dogan, A. | Turkan, A. | Demiroglu-Zergeroglu, A.

Article | 2017 | Turkish Journal of Biochemistry42 ( 5 ) , pp.577 - 585

Aim: Impaired mitochondrial function is a consequence of HIF1-induced overexpression of pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates pyruvate dehydrogenase multi-enzyme complex (PDC), which converts pyruvate to acetyl-CoA for entry into the TCA cycle. Shifting cancer cells from glycolysis to oxidative phosphorylation induces apoptosis, which is a new therapeutic strategy by utilizing PDK inhibitors. In this work, the effect of PDK inhibitor, dichloroacetate (DCA) has been investigated in Human renal carcinoma cell line. Methods: Adherent epithelium renal cell adenocarcinoma (ACHN) cells were treated with . . .different concentrations of DCA at different time periods. Cell viability was measured by WST assay, cell-cycle profile and apoptosis were assessed by using flow cytometry. Metabolites of the cell extracts were analyzed by LC-MS/MS. Results: DCA reduced cell viability in a concentration- and time-dependent manner. Treatment with DCA induced G1 arrest and apoptosis in ACHN cells. Additionally, metabolite changes of ACHN cell line upon DCA treatments showed that lactate, citrate, N-acetylaspartate and 5-oxoproline levels, which were high in untreated cells, significantly reduced upon DCA treatment. Conclusion: Potential anti-carcinogenic effects of DCA, including inhibition of cell proliferation and growth, and induction of apoptosis, as well as the ability of markedly reducing lactate levels make this agent a promising drug candidate in renal adenocarcinomas. © 2017, Turkish Biochemistry Society. All rights reserved Daha fazlası Daha az

Gurdal, E.E. | Buclulgan, E. | Durmaz, I. | Cetin-Atalay, R. | Yarim, M.

Article | 2015 | Anti-Cancer Agents in Medicinal Chemistry15 ( 3 ) , pp.382 - 389

Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Aroyl substituted compounds 1h and 1j were found to be the most active derivatives. In addition, further investigation of compounds 1h and 1j by Hoechst staining and FACS revealed that these compoun . . .ds cause apoptosis by cell cycle arrest at subG1 phase. © 2015 Bentham Science Publishers Daha fazlası Daha az

Maroufi, N.F. | Vahedian, V. | Mazrakhondi, S.A.M. | Kooti, W. | Khiavy, H.A. | Bazzaz, R. | Sabzichi, M.

Article | 2020 | Naunyn-Schmiedeberg's Archives of Pharmacology393 ( 1 ) , pp.382 - 389

The harmful dose-dependent side effects of chemotherapy drugs have caused the discovery of novel perspective to evaluate chemotherapy protocols. In this study, the potential application of Compritol was investigated as a major scaffold into nanostructured lipid careers to highlight myricetin efficiency in treatment of breast cancer cells along with codelivery of docetaxel (DXT). Characterization of myricetin-loaded NLCs was carried out by measuring the particle size and zeta potential, using the scanning electron microscopy. MTT, DAPI staining, flow cytometric, and RT-PCR (real-time) assays were used to recognize novel formulation b . . .ehavior on cell cytotoxicity as well as recognizing molecular mechanism of formulation concerning apoptosis phenomenon. Myricetin-loaded NLCs reduced the cell viability from 50 ± 2.3 to 40 ± 1.3% (p < 0.05). Percentage of apoptosis improved with combination treatment of myricetin-loaded NLCs and DXT in the MDA-MBA231 breast cancer cells. Expression of antiapoptotic genes (survivin, Cyclin B1, and Mcl1) indicated a significant reduction in factor along with increment in proapoptotic factor Bax and Bid mRNA rates. Overall, our results represented that the NLC delivery system could be a promising strategy to enhance the effect of anticancer agents such as DXT on breast cancer. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature Daha fazlası Daha az

Göker, B. | Özsavci, D. | Şener, A. | Aksoy, H. | Bagişgil, V. | Yanikkaya-Demirel, G. | Uras, F.

Article | 2011 | Marmara Pharmaceutical Journal15 ( 1 ) , pp.38 - 42

During storage of platelet obtained by apheresis several changes occur. The aim of this study was to investigate the effect of storage on activation, apoptosis, protein pattern, lipid peroxidation, and the levels of nitric oxide (NO) and glutathione (GSH) of platelets. In this study, platelets obtained from healty donors (n=7) by apheresis were kept in an agitator for nine days at 20-24°C. The samples were taken on the 1st, 3 rd, 5 th and 9 th days and platelets were precipitated. Platelet activation with PAC-1 and CD62-P antibodies and platelet apoptosis were measured with Annexin-V using flow cytometer. Platelets were frozen and t . . .hawed four times and then NO, GSH and malondialdehyte (MDA) levels were assayed by spectrophotometry. Platelets protein pattern was investigated via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) procedure. When compared to the 1st day, platelet CD62-P, PAC- 1 expressions and Annexin-V levels significantly increased on the 3rd, 5th and 9th days, while platelet NO and GSH levels significantly decreased on the 3rd, 5th and 9th days. Furthermore MDA levels significantly increased on only the 5th and 9th days. Mild changes occurred in the density of platelet protein bands. In conclusion, our results show that alterations of platelet activity during storage period may enhance platelet procoagulant activity which increases trombogenic risk. Therefore, for transfusion using fresh platelets or adjusting platelet preservation are strongly important for platelet behavior in vivo conditions Daha fazlası Daha az

Verimli, N. | Demiral, A. | Yılmaz, H. | Çulha, Mustafa | Erdem, S.S.

Article | 2019 | Applied Biochemistry and Biotechnology189 ( 3 ) , pp.709 - 728

Dense brush conformation–bearing theranostic agents are emerging as drug delivery systems due to their higher ability to escape from reticuloendothelial system uptake which prolongs their in vivo circulation time. With the aim of developing dual therapy agent, 13-nm gold nanoparticles’ (AuNPs) surfaces were coated with different amounts of polyethylene glycol (PEG) (SH-PEG-NH2) to obtain dense brush conformation–bearing theranostic agents. Among the 14 different theranostic agent candidates prepared, the one hosting 1819 PEG per particle was selected as the most promising theranostic agent candidate based on structural conformation, . . . stability, size, zeta potential, hemocompatibility, cell inhibition, and cell death pathway towards MCF-7 cell line. To test drug delivery efficiency of the developed PEGylated AuNP and to improve efficacy of the treatment, apoptotic peptide (AP) was covalently conjugated to NH2 terminus of the PEG in various ratios to yield AuNP-AP conjugate. Among the prepared conjugates, the one having 1 nmol of peptide per milliliter of AuNP yielded the most promising results based on the same criteria as employed for PEGylated AuNPs. Besides, incorporation of AP to AuNP returned in superior efficacy of AP since it was possible to achieve 50% cell death with 1000 times less amount of AP alone. © 2019, Springer Science+Business Media, LLC, part of Springer Nature Daha fazlası Daha az

Coskun, Z.M. | Ersoz, M. | Acikgoz, B. | Karalti, I. | Cobanoglu, G. | Sesal, C.

Article | 2015 | Folia Biologica (Czech Republic)61 ( 3 ) , pp.97 - 103

This study tries to elucidate the anti-prolif-erative and apoptotic effects of methanolic lichen extracts from Cladonia rangiformis and Cladonia convolute in MCF-7 human breast cancer cells. Lichen extracts (0-2 mg/ml) were added to MCF-7 cells for 24 h. Cell viability was tested using 3-(4,5-dimethyl-thiazol-2-yl)-2,5 diphenyltetrazolium bromi de (MTT) assay. Cell proliferation was observed using bromo-deoxyuridine (BrdU) labelling and proliferating cell nuclear antigen (PCNA) by immunocytochemistry. The TUNEL method was used for cell death detection. The effective dose (ED50) values of methanolic extracts from C. rangiformis and C . . .. convolute were found to be 0.905 and 0.977 mg/ml, respectively. Treatment with C. rangiformis methanolic extract (0.2-0.8 mg/ml) dose-dependently inhibited proliferation of MCF-7 cells as detected by BrdU incorporation. The inhibition was started in 0.2 mg/ml concentration of C. convoluta methanolic extract. The percent of PCNA immunopositive cells showed a decrease in MCF-7 cells treated with two lichen extracts compared to control MCF-7. Both methanolic extracts showed a significant increase in percentage of apoptosis-positive cells. These results indicate that methanolic lichen extracts from C. rangiformis and C. convolute inhibited proliferation of MCF-7 cells and caused apoptosis in MCF-7 cells. The lichens may be novel natural agents for treating breast cancer disease Daha fazlası Daha az

Yazihan, N. | Kocak, M.K. | Akcil, E. | Billur, D. | Ermis, E. | Cesaretli, Y. | Uzunalimoglu, O.

Article | 2015 | Trace Elements and Electrolytes32 ( 4 ) , pp.211 - 220

Accumulation of cadmium (Cd) which is a wide spread environmental toxin results in toxicity of tissues. Liver is one of the most affected tissues by Cd exposure. Cd exposure induces inflammation in affected tissues. Galectin-3 is an inflammation related molecule, which takes part in cell survival, apoptosis and migration. The present study focused on the role of proinflammatory levels in Cd toxicity and their relationships with galectin-3 levels. Male Wistar rats were exposed to Cd at the dose of 15 ppm for 8 weeks. Inflammatory status in liver was evaluated by measuring the tissue tumor necrosis factor-? (TNF-?), interleukin 1ß (IL . . .-1ß), and interleukin-8 (IL-8) levels. Liver tissue cytochrome c level was used to identify apoptosis. Hypoxia inducible factor (HIF)-1? and galectin-3 mRNA expression levels were evaluated by RT-PCR. Tissue galectin-3, TNF-?, IL-1ß, and IL-8 levels were evaluated by ELISA. Liver tissue was evaluated histopathologically. A significant increase in galectin-3 tissue level was observed after Cd toxicity, which was accompanied by a significant increase in liver TNF-?, IL-1ß, and IL-8 levels. Cd toxicity resulted in an increase in the cytochrome c levels. Chronic Cd toxicity induced inflammation and apoptosis in rat livers. Cd toxicity led to an increase in galectin-3 production in liver tissues whereas suppresses HIF-1? mRNA expression. The formation of TNF-? and IL-8 at the expense of Cd exposure may likely trigger apoptosis and galectin-3 expression increase. © 2015 Dustri-Verlag Dr. K. Feistle Daha fazlası Daha az

Çevik, D. | Burçin Yılmazgöz, Ş. | Kan, Y. | Akhan Güzelcan, E. | Durmaz, I. | Çetin-Atalay, R. | Kırmızıbekmez, H.

Article | 2018 | Industrial Crops and Products124 , pp.389 - 396

Licorice (Glycyrrhiza glabra L.) is one of the most widely used plants worldwide for its various pharmacological activities. The aim of this study was to isolate the potential cytotoxic secondary metabolites from the MeOH extract prepared from the roots of Glycyrrhiza glabra through bioactivity-guided isolation procedure and to elucidate their mechanisms of action. The crude MeOH extract as well as CHCl3 and EtOAc subextracts significantly inhibited cell proliferation on hepatocelullar (Huh7), breast (MCF7) and colorectal (HCT116) cancer cell lines with IC50 values in the range of 5.6 to 33.6 µg/mL. Chromatographic seperations of th . . .e CHCl3 and EtOAc subextracts yielded 13 secondary metabolites. Structures were characterized based on NMR and MS data. Amongst isolates, glabridin (1), 4'-O-methylglabridin (2), ß-amyrin (3), kanzonol U (4), glabrene (7) and tetrahydroxymethoxychalcone (10) were established to be responsible for in vitro cytotoxicity of G. glabra, exerting the best activity particularly against Huh7 cells. Further mechanistic studies demonstrated that 2 and 7 induced caspase-dependent apoptosis by increasing cytochrome C release and subsequently cleaved caspase-9 level in Huh7 cells. Moreover, both compounds decreased pRb and p21 levels and thus induced the accumulation of Huh-7 cells in subG1 and G2/M phases. Compound 10 which displayed the most potent activity in Hoechst staining and cell cycle assays through G2/M arrest, caused cell death by apoptosis in Huh7 cells. © 2018 Elsevier B.V Daha fazlası Daha az

Özdemir-Kumral, Z.N. | Erkek, B.E. | Karakuş, B. | Almacı, M. | Fathi, R. | Yüksel, M. | Alican, İ.

Article | 2019 | Journal of Surgical Research243 , pp.165 - 172

Background: 1,25 Dihydroxyvitamin D3 (1,25(OH)2D3) modulates inflammation and immune responses. Deficiency of 1,25(OH)2D3 was found to be associated with the risk of cancer, cardiovascular disease, osteoarthritis, infections, and autoimmune diseases. This study evaluated the effect of 1,25 dihydroxyvitamin D3 1,25(OH)2D3 on thioacetamide (TAA)-induced acute liver injury in rats. Materials and methods: Rats were treated with either saline or 1,25(OH)2D3 (0.30 µg/kg; orogastrically) for 15 d. Starting from day 13, TAA (200 mg/kg; intraperitoneally) was given for 3 d. On day 15, all rats were euthanized. Liver and blood samples were co . . .llected. Results: TAA caused severe damage, increased lipid peroxidation with reductions in endogenous antioxidants, increased apoptosis, increased production of reactive oxygen species, and elevated inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-?B) expression in liver. Extent of damage was decreased by 1,25(OH)2D3 (P < 0.01). 1,25(OH)2D3 attenuated the increase in malondialdehyde (P < 0.01), increase in myeloperoxidase (P < 0.01), increase in chemiluminescence levels (P < 0.05) and apoptotic activity (P < 0.001). Elevated liver iNOS and NF-?B expression in TAA group was also reduced by 1,25(OH)2D3 (P < 0.001, for iNOS; P < 0.001, for NF-?B). TAA group revealed high serum aspartate transaminase and alanine transaminase (ALT) activities (P < 0.01, for aspartate transaminase; P = 0.08, for ALT) and reduced albumin levels (P < 0.01) compared with control. 1,25(OH)2D3 had no statistically significant effect on these parameters. Conclusions: 1,25(OH)2D3 provides protection against hepatic injury in a rat model of TAA-induced hepatotoxicity via suppression of inflammatory reaction, oxidative stress, and apoptosis. © 2019 Elsevier Inc Daha fazlası Daha az

Onen-Bayram, F.E. | Durmaz, I. | Scherman, D. | Herscovici, J. | Cetin-Atalay, R.

Article | 2012 | Bioorganic and Medicinal Chemistry20 ( 17 ) , pp.5094 - 5102

The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ~5 µM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptot . . .ic pathway, which is death receptor independent. © 2012 Elsevier Ltd. All rights reserved Daha fazlası Daha az

Küçükgüzel, Ş.G. | Koç, D. | Çikla-Süzgün, P. | Özsavci, D. | Bingöl-Özakpinar, Ö. | Mega-Tiber, P.D.L.D.A.L. | Şahin, Fikrettin

Article | 2015 | Archiv der Pharmazie348 ( 10 ) , pp.730 - 742

Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, 1H NMR) methods. N'-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76 µM against colon cancer line HT-29 (ATCC, HTB-38) and did n . . .ot display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site. The tolmetin hydrazone N'-[(2,6-dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) exhibited anticancer activity with an IC50 value of 76 µM against HT-29 cells and did not display cytotoxicity toward control fibroblast cells, compared to tolmetin. The anti-cancer activity of 4g was shown to be due to the activation of caspase-8 and caspase-9 involved in apoptosis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Daha fazlası Daha az