Person: YILMAZ GÖLER, AYŞE MİNE
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YILMAZ GÖLER
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AYŞE MİNE
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Publication Open Access Anti-cancer effects of curcumin, quercetin and tea catechins(MARMARA UNIV, FAC PHARMACY, 2016-09-20) YALÇIN, AHMET SUHA; Yalcin, A. Suha; Yilmaz, Ayse Mine; Altundag, Ergul Mutlu; Kocturk, SemraPolyphenols are present in high amounts in all parts of plants including roots, seeds, flowers, leaves, branches and trunk as well as plant derived products such as tea, coffee and wine. Extensive amount of information is available on biological effects of polyphenols including antioxidant, anti-cancer, anti-inflammatory, anti-coagulant and anti-microbial activities. In recent years, researchers have turned their interest towards identifying molecular mechanisms underlying the anti-cancer effects of these compounds. However, the limited bioavailability of polyphenols and the existence of differences in cancer cells in terms of intracellular mechanisms affected has necessitated the use of specific approaches to individual cancer cell types as well as methods of increasing bioavailability. In this review, the structures, bioavailability, biological activities and molecular mechanisms of anti-cancer effects of curcumin, quercetin and tea catechins are discussed.Publication Open Access Cytotoxicity of Different Nano Composite Resins on Human Gingival and Periodontal Ligament Fibroblast Cell Lines: An In Vitro Study(MDPI, 2020-03-01) YILMAZ GÖLER, AYŞE MİNE; Kavuncu, Gamze; Yilmaz, Ayse Mine; Yilmaz, Betul Karademir; Atali, Pinar Yilmaz; Altunok, Elif Cigdem; Kuru, Leyla; Agrali, Omer BirkanThe aim of this study is to determine the cytotoxicity of three different nano composite resins (CRs) on human gingival fibroblast (hGF) and periodontal ligament fibroblast (hPDLF) cell lines. These CRs selected were nanohybrid organic monomer-based Admira Fusion (AF), nanohybrid Bis-(acryloyloxymethyl) tricyclo [5.2.1.0.sup.2,6] decane-based Charisma Topaz (CT), and supra nano filled resin-based Estelite Quick Sigma (EQS). MTT assay was performed to assess the cytotoxicity of CRs at 24 h and one week. AF and EQS applied on hGF cells at 24 h and one week demonstrated similar cytotoxic outcomes. Cytotoxicity of CT on hGF cells at one week was higher than 24 h (p = 0.04). Cytotoxicity of CT on hGF cells was higher at 24 h (p = 0.002) and one week (p = 0.009) compared to control. All composites showed higher cytotoxicity on hPDLF cells at one week than the 24 h (AF; p = 0.02, CT; p = 0.02, EQS; p = 0.04). AF and EQS demonstrated lower cytotoxicity on hPDLF cells than the control group at 24 h (AF; p = 0.01, EQS; p = 0.001). CT was found more cytotoxic on hPDLF cells than the control (p = 0.01) and EQS group (p = 0.008) at one week. The cytotoxicity of CRs on hGF and hPDLF cells vary, according to the type of composites, cell types, and exposure time.Publication Open Access Klorheksidinin insan dişeti fibroblastları üzerindeki hücre canlılığı ve sitotoksisite etkinliğinin in vitro koşullarda değerlendirilmesi(2023-04-01) YILMAZ GÖLER, AYŞE MİNE; ÖZTÜRK ÖZENER, HAFİZE; Bayraktar G., YILMAZ GÖLER A. M., ÖZTÜRK H.Amaç: Bu in vitro çalışmada, % 0,2’lik klorheksidin (CHX) solüsyonunun, insan dişeti fibroblast (HGF) hücre canlılığı ve sitotoksisitesi üzerindeki etkilerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Bu çalışma 30 saniye ve 2 dakikalık zaman aralıklarında, nötr pH değerindeki % 0,2’lik CHX solüsyonu ve hücre olarak ATCC’den ticari olarak temin edilen HGF-1 (CRL2014) hücre hatları kullanılarak gerçekleştirildi. CHX’in HGF üzerindeki hücre canlılığı etkileri 3-(4,5-dimetiltiazol-2-il)-2,5- difeniltetrazolyum bromür (MTT) testi ile ve sitotoksik etkileri laktat dehidrogenaz (LDH) testi ile değerlendirildi. Sonuçlar ortalama ve standart sapma değerleri kullanılarak two way ANOVA testiyle istatistiksel olarak analiz edildi (p<0,05). Bulgular: MTT testi sonuçlarına göre, % 0,2 CHX solüsyonunun zamanla hücre canlılığını azalttığı görüldü (p<0,0001). LDH testi sonuçlarına göre ise % 0,2 CHX’in sitotoksik etkinliğinin kontrol grubuna kıyasla arttığı (p<0,0001) ancak zaman içinde istatistiksel olarak anlamlı bir fark göstermediği (p>0,05) gözlendi. Sonuç: Bu in vitro çalışmanın sınırları dahilinde, % 0,2 CHX solüsyonu, 30 sn ve 2 dk’lık kısa maruz kalma sürelerinde, HGF hücre canlılığını azalttı ve HGF üzerinde sitotoksik etki gösterdi.Publication Open Access Effect of different immobilization media on breakdown of whey proteins by Streptococcus thermophilus(2022-05-01) YILMAZ GÖLER, AYŞE MİNE; Safak F. Z., Bıcım G., Yılmaz A. M., Aksu M. B., Yalcın A. S.Objective: In this study, we aimed to compare the efficiency of different immobilization media to facilitate breakdown of whey proteins by Streptococcus thermophilus (S. thermophilus). Materials and Methods: S. thermophilus was isolated from yoghurt. High-protein whey powder was present in fermentation media and two-phase dispersion technique was used for immobilization of S. thermophilus in agar, agarose and κ-carrageenan. Total protein after fermentation of whey proteins with S. thermophilus in different media was measured. We have also performed sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis to observe changes in individual whey proteins after fermentation in different media. Results:Total protein concentration showed a significant decrease at the end of 24 hours of fermentation in all media. SDS-PAGE results showed that the amount of both α-lactalbumin and β-lactoglobulin were reduced in all immobilization media compared to control. The effect of κ-carrageenan was considerably higher compared to other media. Conclusion:Our results showed that immobilization in κ-carrageenan increased the breakdown of whey proteins by S. thermophilus and can be used to increase fermentation efficiencyPublication Open Access Exploring the anticancer effects of brominated plastoquinone analogs with promising cytotoxic activity in MCF-7 breast cancer cells via cell cycle arrest and oxidative stress induction(2022-06-01) YILMAZ GÖLER, AYŞE MİNE; YILMAZ, BETÜL; Jannuzzı A. T., Yılmaz Göler A. M., Bayrak N., Yıldız M., Yıldırım H., Yılmaz B., Shilkar D., Jayaprakash Venkatesan R., Jayaprakash V., Tuyun A. F.Plastoquinone analogs are privileged structures among the known antiproliferative natural product-based compound families. Exploiting one of these analogs as a lead structure, we report the investigation of the brominated PQ analogs (BrPQ) in collaboration with the National Cancer Institute of Bethesda within the Developmental Therapeutics Program (DTP). These analogs exhibited growth inhibition in the micromolar range across leukemia, non-small cell lung cancer (EKVX, HOP-92, and NCI-H522), colon cancer (HCT-116, HOP-92), melanoma (LOX IMVI), and ovarian cancer (OVCAR-4) cell lines. One brominated PQ analog (BrPQ5) was selected for a full panel five-dose in vitro assay by the NCI’s Development Therapeutic Program (DTP) division to determine GI50, TGI, and LC50parameters. The brominated PQ analog (BrPQ5) displayed remarkable activity against most tested cell lines, with GI50values ranging from 1.55 to 4.41 µM. The designed molecules (BrPQ analogs) obeyed drug-likeness rules, displayed a favorable predictive Absorption, Distribution, Metabolism, and Excretion (ADME) profile, and an in silico simulation predicted a possibleBrPQ5interaction with proteasome catalytic subunits. Furthermore, the in vitro cytotoxic activity ofBrPQ5was assessed, and IC50values for U-251 glioma, MCF-7 and MDA-MB-231 breast cancers, DU145 prostate cancer, HCT-116 colon cancer, and VHF93 fibroblast cell lines were evaluated using an MTT assay. MCF-7 was the most affected cell line, and the effects ofBrPQ5on cell proliferation, cell cycle, oxidative stress, apoptosis/necrosis induction, and proteasome activity were further investigated in MCF-7 cells. The in vitro assay results showed thatBrPQ5caused cytotoxicity in MCF-7 breast cancer cells via cell cycle arrest and oxidative stress induction. However,BrPQ5did not inhibit the catalytic activity of the proteasome. These results provide valuable insights for further discovery of novel antiproliferative agents.Publication Open Access Analysis of quinolinequinone analogs with promising cytotoxic activity against breast cancer(2023-01-01) YILMAZ GÖLER, AYŞE MİNE; YILMAZ GÖLER A. M., Tarbin Jannuzzi A., Biswas A., Mondal S., Basavanakatti V. N., Jayaprakash Venkatesan R., YILDIRIM H., Yıldız M., ÇELİK ONAR H., BAYRAK N., et al.It is quite challenging to find out bioactive molecules in the vast chemical universe. Quinone moiety is a unique structure with a variety of biological properties, particularly in the treatment of cancer. In an effort to develop potent and secure antiproliferative lead compounds, five quinolinequinones (AQQ1-5) described previously have been selected and submitted to the National Cancer Institute (NCI) of Bethesda to envisage their antiproliferative profile based on the NCI Developmental Therapeutics Program. According to the preliminary in vitro single-dose anticancer screening, four of five quinolinequinones (AQQ2-5) were selected for five-dose screening and they displayed promising antiproliferative effects against several cancer types. All AQQs showed a excellent anticancer profile with low micromolar GI50 and TGI values against all leukemia cell lines, some non-small cell lung and ovarian cancer, most colon, melanoma, and renal cancer, and in addition to some breast cancer cell lines. AQQ2-5 reduced the proliferation of all leukemia cell lines at a single dose and five additional doses, as well as some non-small cell lung and ovarian cancer, the majority of colon cancer, melanoma and renal cancer, and some breast cancer cell lines. This motivated us to use in vitro, in silico, and in vivo technologies to further investigate their mode of action. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ3, in HCT-116 colon cancer, MCF7 and T-47D breast cancer, and DU-145 prostate cancer cell lines, and HaCaT human keratinocytes. Concomitantly, IC50 values of AQQ2 and AAQ3 against MCF7 and T-47D cell lines of breast cancer, DU-145 cell lines of prostate cancer, HCT-116 cell lines of colon cancer, and HaCaT human keratinocytes were determined. AQQ2 exhibited anticancer activity through the induction of apoptosis and caused alterations in the cell cycle. In silico pharmacokinetic studies of all analogs have been carried out against ATR, CHK1, WEE1, CDK1, and CDK2. In addition to this, in vitro ADME and in vivo pharmacokinetic profiling for the most effective AAQ (AAQ2) have been studied.Publication Open Access Higher proteotoxic stress rather than mitochondrial damage is involved in higher neurotoxicity of bortezomib compared to carfilzomib(ELSEVIER, 2020-05) YILMAZ GÖLER, AYŞE MİNE; Jannuzzi, Ayse Tarbin; Arslan, Sema; Yilmaz, Ayse Mine; Sari, Gulce; Beklen, Hande; Mendez, Lucia; Fedorova, Maria; Arga, Kazim Yalcin; Yilmaz, Betul Karademir; Alpertunga, BuketProteasome inhibitors have great success for their therapeutic potential against hematologic malignancies. First generation proteasome inhibitor bortezomib induced peripheral neuropathy is considered as a limiting factor in chemotherapy and its second-generation counterpart carfilzomib is associated with lower rates of neurotoxicity. The mitochondrial toxicity (mitotoxicity) hypothesis arises from studies with animal models of bortezomib induced peripheral neuropathy. However, molecular mechanisms are not fully elucidated and the role of mitotoxicity in bortezomib and carfilzomib induced neurotoxicity has not been investigated comparatively. Herein, we characterized the neurotoxic effects of bortezomib and carfilzomib at the molecular level in human neuronal cells using LC-MS/MS analysis, flow cytometry, RT-qPCR, confocal microscopy and western blotting. We showed that bortezomib and carfilzomib affected the human neuronal proteome differently, and bortezomib caused higher proteotoxic stress via protein oxidation, protein K48-ubiquitination, heat shock protein expression up-regulation and reduction of mitochondria membrane potential. Bortezomib and carfilzomib did not affect the gene expression levels related to mitochondrial dynamics (optic atrophy 1; OPA1, mitofusin 1; MFN1, mitofusin 2; MFN2, fission 1; FIS1, dynamin-related protein 1; DRP1) and overall mitophagy rate whereas, PINK1/Parkin mediated mitophagy gene expressions were altered with both drugs. Bortezomib and carfilzomib caused downregulation of the contents of mitochondrial oxidative phosphorylation complexes, voltage-dependent anion channel 1 (VDAC1) and uncoupling protein 2 (UCP2) similarly. Our findings suggest that, both drugs induce mitotoxicity besides proteotoxic stress in human neuronal cells and the higher incidence of neurotoxicity with bortezomib than carfilzomib is not directly related to mitochondrial pathways.Publication Open Access Ubiquitin proteasomal system is a potential target of the toxic effects of organophosphorus flame retardant triphenyl phosphate(2022-11-01) YILMAZ GÖLER, AYŞE MİNE; Jannuzzı A. T. , Yılmaz Göler A. M. , Alpertunga B.© 2022 Elsevier B.V.The consumption of the widely used flame retardant Triphenyl phosphate (TPP) is increasing. It is now frequently detected in the environment and also domestically. Although the possibility of dermal exposure to TPP is quite high, little is known about its potential molecular toxicity mechanisms. In this study, we found that TPP caused cytotoxicity on human skin keratinocytes (HaCaT) and significantly inhibited the proliferation and cell migration in a concentration-dependent manner. Additionally, HaCaT cells were sensitive to TPP-induced apoptosis. Reactive oxygen species production was induced with TPP, which increased the protein carbonylation and lipid peroxidation levels. Moreover, TPP inhibited proteasome activity and increased the accumulation of ubiquitinated proteins. Exposure to TPP significantly increased the HSP90, HSP70, GRP94 and GRP78 protein levels. Overall, our findings indicate that TPP may pose a risk to human health and contribute to the current understanding of the risks of TPP at the molecular level.Publication Open Access Effect of ketone bodies on viability of human breast cancer cells (MCF-7)(MARMARA UNIV, FAC MEDICINE, 2018-06-05) YALÇIN, AHMET SUHA; Kaya, Zuhal; Yilmaz, Ayse Mine; Yalcin, A. SuhaObjective: Cancer cells exhibit an elevated glycolytic phenotype under aerobic conditions, which is known as the Warburg effect. Recent studies have also shown that cancer cells are glucose-dependent and cannot use ketone bodies as a primary source of energy. In this study, we have investigated the effects of ketone bodies on viability of breast cancer cells considering that breast cancer cells would not use ketone bodies as a primary energy source. Materials and Methods: In this study we have used MCF-7 cells, which are breast cancer cells that cannot use ketone bodies as a primary energy source and human foreskin fibroblast cells (HFF) as controls. We measured cell viability in both cells cultured in the presence or absence of glucose as well as the ketone bodies acetoacetate and beta-hydroxybutyrate. Results: Cell viability was significantly decreased in response to ketone bodies compared with control media in MCF-7 cells whereas in control cells (HFF) cell viability was not changed. Conclusion: In light of the data obtained, we suggest that dietary manipulation with the use of ketone bodies may be a new therapeutic strategy for breast cancer.Publication Open Access Synergistic Effects of Methotrexate and Suberoylanilide Hydroxamic Acid in Triggering Apoptosis of Chronic Myeloid Leukemia Cells(AKAD DOKTORLAR YAYINEVI, 2015-03-30) YALÇIN, AHMET SUHA; Altundag, Ergul M.; Yilmaz, Ayse M.; Corek, Ceyda; Yalcin, A. Suha; Taga, Yavuz; Kocturk, SemraIn this study, we have investigated the effects of suberoylanilide hydroxamic acid (SAHA) against chronic myeloid leukemia (CML) cells in combination studies with methotrexate (MTX), which is a dihydrofolate reductase inhibitor used in combination therapy with other agents or alone. Combination of synergistic ratios of MTX and SAHA led to apoptotic cell death of CML cells via PARR cleavage, cytochrome c release and ROS increase in vitro. We suggest that combination of MD( and SAHA may minimize the toxicity and side effects of SAHA treatment, thus providing lower amounts of each drug in CML treatment.