Browsing by Author "Gunduz C."

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    Antileishmanial activity of selected Turkish medicinal plants
    (University of Benin, 2014) Ozbilgin A.; Durmuskahya C.; Kayalar H.; Ertabaklar H.; Gunduz C.; Ural I.O.; Zeyrek F.; Kurt O.; Cavus I.; Balcıoglu C.; Toz S.O.; Ozbel Y.
    Purpose: To determine the in vitro and in vivo anti-leishmanial activities of extracts obtained from Centaurea calolepis, Phlomis lycia, Eryngium thorifolium, Origanum sipyleum and Galium incanum ssp. centrale.; Methods: To estimate the cytotoxicity of plant extracts, WST-1 assay was used. Parasite inhibition in the presence of plant extracts (25-500 μg/ml) in comparision with control group and reference group (glucantime, 25 μg/ml) at 12-72 h were determined in vitro on L. tropica promastigotes. The in vivo leishmanicidal activity of the extracts was evaluated against L. tropica-infected mice with glucantime as reference drug.; Results: The chloroform extract of Galium incanum ssp. centrale showed the highest cytotoxicity with IC50 value of 0.0316 ± 0.005 μg/ml. In vitro parasite inhibition by the plant extracts ranged between 16.7 ± 0.01 % and 100 ± 0.00 % at 25 μg/ml concentration. The methanol extract of Eryngium thorifolium possessed the highest activity on promastigotes of L. tropica with 100 % inhibition at 25 μg/ml. The water and chloroform extracts of C. calolepis and water and methanol extracts of E. thorifolium at a dose of 100 mg/kg reduced parasitaemia in L. tropica infected mice.; Conclusion: Parasite viability results suggest that the methanol extract of Eryngium thorifolium, regarded as non-cytotoxic, is a promising candidate drug for treating L. tropica infection. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.
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    Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes
    (Zerbinis Publications, 2014) Goker B.; Caliskan C.; Caglar H.O.; Kayabasi C.; Balci T.; Tepedelen B.E.; Aygunes D.; Susluer S.Y.; Mutlu Z.; Gunell N.S.; Korkmaz M.; Saydam G.; Gunduz C.; Avci C.B.
    Purpose: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that inhibition of BCR-ABL fusion protein by ponatinib induces apoptosis of CML cells. Epigallocatechin-3-gallate (EGCG), which is a polyphenol in green tea, induces apoptosis in different types of cancer cells. The purpose of this study was to determine the cytotoxic and apoptotic effects of ponatinib and EGCG combination in K562 CML cell line. This study also aimed to detect alterations of the expression levels of cell cycle-regulation related genes after ponatinib and EGCG combination in K562 CML cell line. Methods: The cytotoxic effects of the compounds on K562 cells were determined in a time- and dose-dependent manner by using WST-1 analysis. The combination index (CI) isobologram was used to analyze the data. Apoptotic effects of P-EGCG were defined by flow cytometry and gene expressions were detected by RT-qPCR. Results: IC50 values of ponatinib and EGCG were 87.13 nM and 50μM, respectively. CI value of the P-EGCG was 0.658 and the combination showed synergistic effect (ED90 value: 28.39 nM ponatinib, 117.12 μg/ml EGCG). Ponatinib, EGCG and P-EGCG induced apoptosis compared to control cells. CyclinDl and CDC25A were downregulated by P-EGCG by 2.49 and 2.63-fold, respectively. TGF-β2 was upregulated by 4.57-fold. Conclusion: EGCG possesses cytotoxic and apoptotic properties and may cooperate with the growth inhibiting activity of ponatinib synergistically against CML cells. P-EGCG mediated apoptosis might be associated with upregulation of TGF-β2 gene and downregulation of cyclinDl and CDC25A genes.
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    Disodium pentaborate decahydrate (DPD) induced apoptosis by decreasing hTERT enzyme activity and disrupting F-actin organization of prostate cancer cells
    (IOS Press BV, 2014) Korkmaz M.; Avcı C.B.; Gunduz C.; Aygunes D.; Erbaykent-Tepedelen B.
    Animal and cell culture studies have showed that boron and its derivativesmay be promising anticancer agents in prostate cancer treatment. Thus, DU145 cells were treated with disodium pentaborate decahydrate (DPD) for 24, 48, and 72 h in order to investigate the inhibitor effect and mechanisms of DPD. Then, cell proliferation, telomerase enzyme activity, actin polymerization, and apoptosis were detected by WST-1 assay, qRT-PCR, immunofluorescence labeling, and flow cytometry, respectively. We found that DPD inhibited the growth of human prostate cancer cell line DU145 at the concentration of 3.5 mM for 24 h. Our results demonstrated that 7 mM of DPD treatment prevented the telomerase enzyme activity at the rate of 38%. Furthermore, DPD has an apoptotic effect on DU145 cells which were examined by labeling DNA breaks. With 7 mM of DPD treatment, 8, 14, and 41% of apoptotic cells were detected for 24, 48, and 72 h, respectively. Additionally, immunofluorescence labeling showed that the normal organization of actin filaments was disrupted in DPD-exposed cells, which is accompanied by the alteration of cell shape and by apoptosis in targeted cells. Taken together, the results indicate that DPD may exert its cytotoxicity at least partly by interfering with the dynamic properties of actin polymerization and decreasing the telomerase activity. Eventually, for the first time, the results of this study showed that DPD suppressed the activity of telomerase in DU145 cells, and therefore, we suggested that DPD could be an important agent for its therapeutic potential in the treatment of prostate cancer. © International Society of Oncology and BioMarkers (ISOBM) 2013.
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    Anti-cancer efficiency of natural killer cells differentiated from human adipose tissue-derived mesenchymal stem cells and transfected with miRNA150
    (Morion LLC, 2017) Karlitepe A.; Kabadayi H.; Vatansever S.; Gurdal M.; Gunduz C.; Ercan G.
    Aim: The aim of this study is to investigate the effects of miR150 transfection on NK-like cells differentiated from adipose tissue derived mesenchymal stem cells (AD-MSCs). Methods: NK-like cells were differentiated from AD-MSCs and activated by miR150 transfection. Transfected/non-Transfected NK-like cells were characterized by immunohistochemical and RTPCR analyzes. Apoptotic efficiency of the transfected/non-Transfected NK-like cells on pancreatic cancer cells PANC1 were determined by TUNEL and RT-PCR. Results: In miR150-Transfected cells, the increased expression of NK cell-specific genes such as GKMB, KIR2DL2, CD16, CD56, NKG2D, NKp46 and increased immunoreactivity of NK cell-specific surface marker CD314 (NKG2D) were evident. TUNEL assays showed that NK-like cells with/without transfection induced apoptosis in PANC1 cells in the same manner. The decrease in oncogene expression and the increase in the tumor suppressor gene expression in PANC1 cells upon co-culture with NK-like cells differentiated from AD-MSCs were more prominent following miRNA150 transfection. Conclusion: It was shown in vitro that NK-like cells could be obtained by differentiation from AD-MSCs and their efficiency could be increased via miR150 transfection. The results are encouraging for further clinical studies in improvement of immunotherapeutic approaches for cancer therapy. Copyright © Experimental Oncology, 2017.
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    Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells
    (John Wiley and Sons Inc, 2020) Ozdemir Kutbay N.; Biray Avci C.; Sarer Yurekli B.; Caliskan Kurt C.; Shademan B.; Gunduz C.; Erdogan M.
    Anaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. The success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. In this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT2 Profiler PCR Array. In C643 and SW1736 cell lines, IC50 doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 µM, and 23.17 µM. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes: AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, and RICTOR genes, in the MET and PIO combination-treated cells. In addition, expression levels of tumor suppressor genes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, and ULK2, were found to have increased significantly. The MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. The decreases, particularly, in AKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, and PRKCA expressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets. © 2020 Wiley Periodicals LLC
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    Comparison of the multi-epitope recombinant antigen DIPOL and hydatid fluid for the diagnosis of patients with cystic echinococcosis
    (Elsevier B.V., 2022) Ozturk E.A.; Manzano-Román R.; Sánchez-Ovejero C.; Caner A.; Angın M.; Gunduz C.; Karaman Ü.; Altintas N.; Bozkaya H.; Unalp O.; Dokumcu Z.; Divarci E.; Casulli A.; Altintas N.; Siles-Lucas M.; Unver A.
    The use of serological tests containing multiple immunodominant antigens rather than single antigens have the potential to improve the diagnostic performance in Cystic Echinococcoses (CE) as a complement tool to clear the inconclusive imaging data. Here, we comparatively evaluated the diagnostic value of Hydatid Fluid (HF) and the recently described recombinant multi-epitope antigen DIPOL in IgG-ELISA in a clinically defined cohort of CE patients. The serum samples from 149 CE patients were collected just before surgical or Percutaneous- Aspiration- Injection- Reaspiration (PAIR) procedures. Additionally, serum samples of patients with other parasitic infections (n=49) and healthy individuals (n=21) were also included in the study as controls. To investigate the association between the genotype of the parasite and DIPOL, cyst materials from 20 CE patients were sequenced. In terms of overall sensitivity, HF was higher than DIPOL (82.55%,78.52%, respectively). However, while the sensitivity of HF was higher than DIPOL in patients with active and transitional cysts (83.3%, 75.4%, respectively), sensitivity of DIPOL in inactive cysts was higher compared to HF (95.6%, 78.3%, respectively). The sensitivity of DIPOL depending on cyst stage was statistically significant (P= 0.041). In terms of specificity, DIPOL was found to be better than HF (97.71%, 91.43%, respectively). By genotyping, the majority of 20 patients showed G1 genotype (80%). All patients harboring G3 and G1/G3 cyst genotypes were positive with both antigens, while 87.5% of patients with G1 genotype were seropositive with HF and 75% with DIPOL. The overall sensitivity and high specificity of DIPOL suggest that this recombinant protein containing immunodominant epitopes is a potential substitute for the HF by serological tests for the diagnosis of CE. © 2021
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    Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells
    (Taylor and Francis Ltd., 2022) Kayabasi C.; Yilmaz Susluer S.; Balci Okcanoglu T.; Ozmen Yelken B.; Mutlu Z.; Goker Bagca B.; Caliskan Kurt C.; Saydam G.; Durmuskahya C.; Kayalar H.; Ozbilgin A.; Biray Avci C.; Gunduz C.
    Origanum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose ∼5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G0/G1, S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML. © 2022 Taylor & Francis Group, LLC.
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    Distribution and Phylogenetic Analysis of Subtypes and Alleles of Blastocystis sp. in the Stool Samples Collected from Patients with Gastrointestinal Complaints in İzmir, Turkey
    (Springer Science and Business Media Deutschland GmbH, 2023) Aykur M.; Calıskan Kurt C.; Dirim Erdogan D.; Biray Avcı C.; Vardar R.; Aydemir S.; Girginkardesler N.; Gunduz C.; Dagci H.
    Purpose: Blastocystis sp. is one of the most prevalent intestinal protozoa found in humans and many other animals. The present study aimed to examine the distribution and genetic diversity of Blastocystis sp. in stool samples from patients with gastrointestinal complaints in İzmir, Turkey. Methods: All stool samples of 439 patients with gastrointestinal complaints were examined by native-Lugol and trichrome staining. To investigate the presence of Blastocystis sp. in stool samples, DNA was isolated, and PCR was performed with the barcode region in the SSU rRNA gene. PCR positive samples were sequenced to identify subtypes and alleles of Blastocystis sp. Results: The prevalence of Blastocystis sp. was found to be 16.6% (73/439) in patients with gastrointestinal complaints in İzmir, Turkey. Three different Blastocystis sp. subtypes were identified. ST3 (28/55; 51.0%) was the most common subtype followed by ST2 (19/55; 34.5%) and ST1 (8/55; 14.5%). Itching and diarrhea were the most prominent clinical symptoms in Blastocystis sp. positive patients. When clinical symptoms and subtypes were compared, diarrhea was found in 62.5%, 47.4%, and 46.4% of patients with ST1, ST2, and ST3 subtypes, respectively. In addition, itching was found in 37.5%, 32.1%, and 21.1% of patients with ST1, ST3, and ST2, respectively. Six distinct alleles were identified by allele analysis of Blastocystis 18S rRNA gene: allele 4 for ST1, alleles 9, 11, and 12 for ST2, and alleles 34 and 36 for ST3. In this study, Blastocystis sp. was detected in 16 of 21 districts, including the central and rural districts of İzmir. Although ST1 was detected in central districts, it was not found in rural districts. Conclusion: This study provides comprehensive data on the prevalence and molecular epidemiology of the genetic diversity at the level of subtypes and alleles of Blastocystis sp. in different districts of İzmir province in Turkey. To the best of our knowledge, this is the first study which evaluates the distribution of subtypes and alleles of Blastocystis sp. according to PCR and SSU rRNA gene sequencing in patients with gastrointestinal complaints in different districts of İzmir province in Turkey. © 2023, The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.