Person: YILMAZ GÖLER, AYŞE MİNE
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YILMAZ GÖLER
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AYŞE MİNE
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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 Metadata only Primary adrenal insufficiency in a patient with biallelic QRSL1 mutations(2022-09-01) YILMAZ GÖLER, AYŞE MİNE; GÜRAN, TÜLAY; Dursun F., Genc H. M. , YILMAZ GÖLER A. M. , Tas I., Eser M., Pehlivanoglu C., Yilmaz B. K. , GÜRAN T.Publication 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 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 Metadata only Combination of second-generation proteasome inhibitor carfilzomib with bortezomib in four different breast cancer cell lin(2022-01-01) YILMAZ GÖLER, AYŞE MİNE; ŞAHİN, ALİ; YILMAZ, BETÜL; Altundag E. M., Yilmaz A. M., Sahin A., Yilmaz B.Background: Proteasome inhibitors target different pathways in cells and therefore are promising drugs in cancer therapy. The use of these inhibitors is approved mainly in hematological cancers, and recently many clinical trials and preclinical studies have been conducted on efficacy in solid tumors. Carfilzomib is a second-generation inhibitor and was developed to decrease the side effects of bortezomib. Although there are many valid therapies for breast cancer, resistance and recurrence are inevitable in many cases and the proteasomal system plays an important role in related pathways. Objective: This study is a preliminary work to evaluate the combined effects of bortezomib and carfilzomib in four different breast cancer cells. Methods: MDA-MB-231, MCF-7, UACC-2087, and SKBR-3 cell lines were used. Cell viability was determined using bortezomib and carfilzomib alone and in combination. Combination effect values were determined using the Chou-Talalay method. Apoptosis, proteasome activity, cleaved PARP, and HSP70 expressions were analyzed in the determined doses. Results: The response to the combination of the two inhibitors was different in four cell lines. Apoptosis was significantly higher in combination groups compared to carfilzomib in three cell lines except for SKBR-3, and higher in the combination group compared to bortezomib only in UACC-2087. Combination decreased cleaved PARP levels in MDA-MB-231 and MCF-7 and increased SKBR-3 compared to bortezomib. HSP70 levels decreased in combination with UACC-2087 and SKBR-3 compared to carfilzomib. Conclusion: Taken together, the combination of the two inhibitors was more apoptotic compared to carfilzomib and apoptosis was higher only in UACC-2087 compared to bortezomib. This apoptosis data can not be directly correlated to the degree of proteasome inhibition, PARP cleavage, and HSP70 response.Publication Open Access Effect of whey protein derivatives on cell viability, cell migration and cell cycle phases in MCF-7 cells(2023-01-01) YILMAZ GÖLER, AYŞE MİNE; YALÇIN, AHMET SUHA; Aksoy F. T., YILMAZ GÖLER A. M., Bicim G., Yalcin A. S.Objective: This study aimed to obtain protein derivatives after treatment of whey proteins with hazelnut oil and olive oil and determined their effects on MCF-7 cells. Materials and Methods: Whey proteins obtained from 6% whey powder were treated with hazelnut oil (HO) and olive oil (OO) at a protein to lipid ratio of 1:10 at 60 ̊C for 120 minutes. The protein derivatives formed with whey protein and HO or OO were applied to MCF-7 cancer cells and healthy fibroblasts. The effects of protein derivatives on cell viability, apoptosis, reactive oxygen species (ROS) production, wound healing, cell cycle phase distribution and cell cycle related proteins Akt and p21(Waf1/Cip1) expressions were investigated. Results: Cell viability decreased significantly after 24 h of incubation with WP:OO. The percentage of apoptotic or necrotic cells varied between 5-10% and no statistically significant effect was observed. There was no statistically significant difference in ROS production and colony formation between controls and WP:HO or WP:OO groups. Treatment of cells with WP:OO for 24 h significantly decreased cell migration compared to the control group. G2/M phase was significantly suppressed in WP:OO group compared to the control group. WP:OO also increased the expression of p21(Waf1/Cip1) significantly when compared with the control group. Conclusion: Our results showed that whey protein derivatives applied to MCF-7 cells are cytotoxic and may be useful in breast cancer treatment