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Öğe Antioxidant Properties and Protective Effect of Turkish Propolis on t-BHP-Induced Oxidative Stress in Foreskin Fibroblast Cells(ASSOC PHARMACEUTICAL TEACHERS INDIA, 2018) Misir, Sema; Aliyazicioglu, Yuksel; Demir, Selim; Turan, Ibrahim; Yaman, Serap Ozer; Deger, OrhanObjective: Propolis is an important bee product, rich in polyphenolic compounds. It has antitumoral, antioxidant, antimutagenic, and other useful activities. Biological activities of propolis are generally attributed to its substance of polyphenolic compounds. The aim of this study was to investigate the in vitro antioxidant properties and reduction amount of intracellular reactive oxygen species (ROS) in human normal foreskin fibroblast cells by Turkish propolis ethanolic extract (EEP). Method: Total phenolic and flavonoid contents, reducing power, radical scavenging capacity, and iron chelating activity of EEP were determined using spectrophotometric methods. Intracellular ROS levels were determined by spectrofluorometric analysis with CM-H(2)DCFDA. Results: Our results indicated that antioxidant activity was correlated with the higher total phenolic and flavonoid contents of EEP. The generated ROS levels were significantly decreased by EEP compared to only t-BHP group. Conclusion: Ethanolic propolis extract may be evaluated as a potency antioxidant resource and/or a novel natural agent in food and drug industries.Öğe Antiproliferative and proapoptotic activity of Turkish propolis on human lung cancer cell line(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2016) Demir, Selim; Aliyazicioglu, Yuksel; Turan, Ibrahim; Misir, Sema; Mentese, Ahmet; Yaman, Serap Ozer; Akbulut, Kubra; Kilinc, Kagan; Deger, OrhanCancer is a heterogeneous disease, two of whose characteristic features are uncontrollable cell proliferation and insufficient apoptosis. Various studies have investigated the antiproliferative effects of propolis, a natural bee product, from different countries, and its cytotoxic effects have been attributed to its polyphenol contents. The purpose of this study was to show the cytotoxic effects, and possible mechanisms involved, of ethanolic extract of Turkish propolis (EEP) on the human lung cancer (A549) cell line. Cytotoxic activity of EEP on A549 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic action of EEP on A549 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, endoplasmic reticulum stress using RT-PCR, and caspase activity using luminometric analysis. EEP exhibited selective toxicity against A549 cells compared to normal fibroblast cells. We determined that EEP arrested the cell cycle of A549 cells at the G(1) phase, induced endoplasmic reticulum stress, caspase activity, and apoptosis and reduced mitochondrial membrane potential. These results indicate that Turkish propolis is capable of reducing cancer cell proliferation and may have a promising role to play in the development of new anticancer drugs in the future.Öğe Biomarker potentials of miRNA-associated circRNAs in breast cancer (MCF-7) cells: an in vitro and in silico study(Springer, 2021) Misir, Sema; Hepokur, Ceylan; Aliyazicioglu, Yuksel; Enguita, Francisco J.Breast cancer is a heterogeneous disease, which is the most common malignancy in women. The incidence and mortality rates of breast cancer indicate that it is the leading cause of cancer-related with deaths. circRNAs operate as part of competing endogenous RNAs (ceRNAs) mechanisms, which play critical roles in the different biological processes of breast cancer such as proliferation, migration, and apoptosis. The goal of the present study is to identify the potential predictive biomarker for breast cancer diagnosis in the circRNA network by in vitro and in silico analyzes. 40 miRNAs were obtained from the miRWalk database and their combinatorial target genes (potential ceRNAs) were identified with ComiR. We stated that the cancer-specific circRNA genes in MCF-7 cells using the cancer-specific circRNA (CSDC) database, and obtained the ones showing potential ceRNA activity in our previous analysis among them. Identified genes with remarkable expression differences between BCa and normal breast tissue were determined by the GEPIA database. Moreover, the Spearman correlation test in the GEPIA database was used for the statistical analysis of the relationship between DCAF7 and SOGA1, SOGA1 and AVL 9, DCAF7 and AVL 9 gene pairs. And also, DCAF7, SOGA1, and AVL9 gene expression levels were detected in MCF-7 and MCF-10A cells by RT-qPCR method. DCAF7, SOGA1, and AVL9 gene were significantly more expressed to BCa tissue and MCF-7 cells than normal breast tissue and MCF-10 A cells. And also, DCAF7 and SOGA1, SOGA1 and AVL9, DCAF7 and AVL9 genes pairs were found to be significantly correlated with BCa. These genes may be considered as potential predictive biomarkers to discriminate BCa patients from healthy persons. Our preliminary results can supply a new perspective for in vitro and vivo studies in the future.Öğe Circular RNAs serve as miRNA sponges in breast cancer(Springer Japan Kk, 2020) Misir, Sema; Hepokur, Ceylan; Aliyazicioglu, Yuksel; Enguita, Francisco J.Circular RNAs are a large group of non-coding RNAs with a closed-loop structure. circRNAs play significant roles in many biological processes as miRNA sponges, regulators for gene transcription, combining with RNA-binding proteins and translation of protein. Nowadays, circRNAs have become a research hotspot in the field of cancer and molecular biology. Accumulating evidences have indicated that circRNAs participate in the initiation and development of various cancers such as breast cancer. Breast cancer is a heterogeneous disease, which is the most common malignancy in women. The incidence and mortality rates of breast cancer indicate that it is the leading cause of cancer-related deaths. The goal of the present review is to introduce biogenesis, function characteristics and types of circRNAs, and also their biological functions on breast cancer, especially as miRNA sponges. Additionally, we discuss their use as a new therapeutic target for the treatment of breast cancer.Öğe Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models(Springer, 2021) Matic, Ivana Z.; Ergun, Sercan; Dordic Crnogorac, Marija; Misir, Sema; Aliyazicioglu, Yuksel; Damjanovic, Ana; Dzudzevic-Cancar, HurijaSix extracts were obtained from plant species Hypericum perforatum L., collected at Samsun in Turkey. The aim of this study was to examine the mechanisms of the anticancer activity of these extracts. Methanol, ethyl-acetate and hexane were used as a solvents for extraction from both branch-body part of the plant (extracts 1, 2 and 3) and from plant flowers (extracts 4, 5 and 6). The cytotoxic effects of the extracts were determined against 2D and 3D cancer cell models. Cell cycle changes of treated HeLa cells were analyzed by flow cytometry. Measurements of gene and microRNA expression levels in treated HeLa cells were done by quantitative real time PCR. Five examined extracts (2-6) exerted selective concentration-dependent cytotoxic effects on HeLa, K562, and A549 cancer cells, while the extract 1 exhibited very weak cytotoxicity. The extract 6 showed the highest intensity of cytotoxic activity. All tested extracts (2-6) demonstrated the ability to induce apoptosis in HeLa cells through activation of caspase-3. These extracts remarkably decreased gene expression levels of MMP2, MMP9, TIMP3, and VEGFA in HeLa cells. Flower extracts might have stronger effects on miR128/193a-5p/335 level changes than branch-body extracts. Hypericum perforatum extracts exerted weaker cytotoxic effects on 3D HeLa spheroids when compared with their effects on 2D monolayer HeLa cells. Taken together, results of our research may suggest the promising anticancer properties of the Hypericum perforatum extracts.Öğe Cytotoxic effect of Rosa canina extract on human colon cancer cells through repression of telomerase expression(ELSEVIER SCIENCE BV, 2018) Turan, Ibrahim; Demir, Selim; Kilinc, Kagan; Yaman, Serap Ozer; Misir, Sema; Kara, Hanife; Genc, Berna; Mentese, Ahmet; Aliyazicioglu, Yuksel; Deger, OrhanRosa canina is a member of the genus Rosa that has long been used for medical objectives. Several studies have reported cytotoxic effects of different Rosa species, but there has been only limited investigation of the cytotoxic effect of R. canina. The purpose of the current study was to examine the potential effect of R. canina extract on cell viability, the cell cycle, apoptosis, and the expression of telomerase in human colon cancer (WiDr) cells. The cytotoxic effect of the extract was determined using MIT assay. The mechanism involved in the cytotoxic effect of the extract was then evaluated in terms of apoptosis and the cell cycle using flow cytometry. Mitochondrial membrane potential (MMP) was investigated using the fluorometric method, and expression levels of telomerase were studied using RT-PCR. R. canina extract exhibited a selective cytotoxic effect on WiDr cells compared with normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. R. canina extract significantly repressed telomerase expressions at treatment times of 48 and 72 h in WiDr cells. Our results suggest that R. canina may have considerable potential for development as a novel natural product-based anticancer agent. (C) 2018 Xi'an Jiaotong University. Production and hosting by Elsevier B.V.Öğe Cytotoxic Effect of Turkish Propolis on Liver, Colon, Breast, Cervix and Prostate Cancer Cell Lines(PHARMACOTHERAPY GROUP, 2015) Turan, Ibrahim; Demir, Selim; Misir, Sema; Kilinc, Kagan; Mentese, Ahmet; Aliyazicioglu, Yuksel; Deger, OrhanPurpose: To investigate the total polyphenolic and flavonoid contents, antioxidant power and cytotoxic activity of ethanol extracts of Turkish propolis (EEP). Methods: The total polyphenolic and flavonoid contents of EEP were determined by spectrometric methods. Antioxidant power and cytotoxic activity of EEP were evaluated using ferric reducing antioxidant power (FRAP) and MTT assays, respectively. Results: The total polyphenolic and flavonoid contents, and FRAP value of EEP were 124.6 +/- 1.5 mg gallic acid/g sample dry weight, 42.0 +/- 0.8 mg quercetin/g sample dry weight and 311.0 +/- 2.5 mg trolox/g sample dry weight, respectively. EEP exhibited powerful cytotoxic effects against the five human cancer cell lines. The highest cytotoxic activity of Turkish EEP was demonstrated on PC-3 cell line (IC50 = 20.7 +/- 3.4 mu g/mL). Conclusion: The results demonstrate that EEP is a good source of antioxidant and a natural antitumor agent capable of reducing cancer cell proliferation.Öğe Effect of Turkish Propolis on miRNA Expression, Cell Cycle, and Apoptosis in Human Breast Cancer (MCF-7) Cells(ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, not defined) Misir, Sema; Aliyazicioglu, Yuksel; Demir, Selim; Turan, Ibrahim; Hepokur, CeylanEnriched in flavonoid compounds, phenol acids, and terpene derivatives, propolis has been shown to regulate apoptosis signaling pathways and alter the expression of microRNAs (miRNAs). In the present study, it has been aimed to examine the effects of Turkish propolis on miRNA levels of breast cancer (MCF-7) cells, and its relationship with cell proliferation and apoptosis. Cytotoxic activity of ethanolic propolis extract (EEP) was evaluated using MTT assay. Mechanisms involved in the cytotoxic action of Turkish propolis in MCF-7 cells were investigated with regard to apoptosis and cell cycle using flow cytometry and western blot. Mitochondrial membrane potential (MMP) were evaluated by spectrofluorometric method. miRNA levels were detected by qRT-PCR method. EEP exhibited selective toxicity against MCF-7 cells compared to normal fibroblast cells. EEP increased the cell cycle arrest at the G(1) phase. EEP elevated the apoptotic cell death through increasing pro-apoptotic protein levels (p21, Bax, p53, p53-Ser46, and p53-Ser15), decreasing MMP and altering the expression levels of specific tumor suppressors (miR-34, miR-15a, and miR-16-5p) and oncogenic (miR-21) miRNAs. These data support that Turkish propolis may be evaluated as a potential natural agent for new anticancer drugs in future.Öğe Evaluation of the radioprotective effect of Turkish propolis on foreskin fibroblast cells(MEDKNOW PUBLICATIONS & MEDIA PVT LTD, 2016) Yalcin, Can Ozgur; Aliyazicioglu, Yuksel; Demir, Selim; Turan, Ibrahim; Bahat, Zumrut; Misir, Sema; Deger, OrhanAim of Study: Propolis is a resinous bee product, rich of polyphenolic compounds and flavonoids. It is known that in different geographic zones its chemical composition varies due to the different plant sources. Many biological properties including antimicrobial, antioxidative, anti-inflammatory, antitumoral, antigenotoxic, antimutagenic, cytostatic activities have been ascribed to propolis. These biological effects are predominantly attributed to its content of polyphenols. In this study, we aimed to evaluate the radioprotective effect of ethanolic extract of Turkish propolis. (EETP) against -ray-induced DNA damage on fibroblast cells using comet assay for the first time. Materials and Methods: Fibroblast cells were pretreated 15 and 30 min with concentrations of 100, 200 and 300 g/mL EETP then they were exposed to 3 Gy -rays. Amifostine (synthetic aminothiol compound) was used as a positive control. Results: The results showed a significant decrease in -ray-induced DNA damage on cells treated with EETP and amifostine when compared to only irradiated cells. (P 001). Conclusion: It was concluded that EETP prevent -ray-induced DNA damage in fibroblast cells and might have radioprotective activity.Öğe Identification of a Novel hsa_circ_0058058/miR-324-5p Axis and Prognostic/Predictive Molecules for Acute Myeloid Leukemia Outcome by Bioinformatics-Based Analysis(Mdpi, 2024) Misir, Sema; Ozer Yaman, Serap; Petrovic, Nina; Sami, Ahmad; Akidan, Osman; Hepokur, Ceylan; Aliyazicioglu, YukselSimple Summary Acute myeloid leukemia (LAML) is among the most common types of hematological cancer. In recent years, it has been shown that circular RNA (circRNA) and microRNA (miRNA) can be used as markers for diagnosis and treatment results in tumor development, in the early stages of the tumor or after chemotherapy. This study aimed to identify the disease-related circRNA-miRNA-mRNA network by bioinformatic analysis and investigate the mechanisms in the development and progression of LAML. Bioinformatics analyses identified the hsa_circ_0058058/miR-324-5p axis in LAML and its possible functions in LAML development. It was found that hsa_circ_0058058 could regulate the expression of AP1G1 and SP1 through miR-324-5p to promote angiogenesis, cell cycle, and DNA replication processes. Downregulation of Hsa circ-0058058 may contribute to the anticancer functions of miR-324-5p on LAML tumorigenesis. Upregulation of miR-324-5p could abolish the oncogenic effects of AP1G1 and SP1 on LAML tumorigenesis.These analyses demonstrated their important role by showing that these molecules can be used as a diagnostic biomarker and therapeutic target for the treatment of LAML.Abstract Acute myeloid leukemia (LAML) is one of the most prevalent hematological malignancies. In recent years, while targeted approaches have shown promise in the fight against cancer, the treatability and prognosis of patients remain inadequate due to the shortage of drugs. Noncoding RNAs, especially circular RNA (circRNA) and microRNA (miRNA), have been shown to play a unique role in tumor development. This study aims to identify the disease-associated circRNA-miRNA-mRNA network by bioinformatic analysis and investigate the mechanisms in the development and progression of LAML. Additionally, it reveals the promising roles of these molecules as a diagnostic biomarker and therapeutic target for LAML treatment. Using various bioinformatics approaches, we identified the hsa_circ_0058058/miR-324-5p axis in LAML and its possible functions in LAML development. According to our results, hsa circ-0058058 can regulate the expression of AP1G1 and SP1 through miR-324-5p to support angiogenesis, the cell cycle, and DNA replication processes. Downregulation of hsa circ-0058058 may contribute to the anticancer functions of miR-324-5p on LAML tumorigenesis, and upregulation of miR-324-5p can abolish the oncogenic effects of AP1G1 and SP1 on LAML tumorigenesis. Additionally, highly enriched pathways indicated possible interactions between molecules underlying LAML pathology. Targeted molecules within this network may be able to function as therapeutic and diagnostic biomarkers for disease, while more research and clinical confirmation are needed.Öğe Morus rubra Extract Induces G(1) Cell Cycle Arrest and Apoptosis in Human Lung and Prostate Cancer Cells(ASSOC PHARMACEUTICAL TEACHERS INDIA, 2017) Turan, Ibrahim; Demir, Selim; Kilinc, Kagan; Aliyazicioglu, Yuksel; Alver, Ahmet; Misir, Sema; Yaman, Serap Ozer; Akbulut, Kubra; Mentese, Ahmet; Deger, OrhanObjective: Cancer is one of the most deadly types of disease and evasion from apoptosis and unstoppable cell proliferation are accepted as its distinctive features. Many studies have evaluated the cytotoxic effect of different Morus species but, there is no study about cytotoxic effect of Morus rubra. In this study we aimed to evaluate phenolic composition, antioxidant properties and cytotoxic effect of acidified dimethyl sulfoxide extract of M. rubra (AMRE). Method: Antioxidant properties, phenolic composition and cytotoxic effect of AMRE were determined using spectrophotometric methods, HPLC, and MTT assay, respectively. Then, mechanisms of cytotoxic effect of AMRE on human prostate (PC-3) and lung (A549) cancer cells were examined in regard to cell cycle, apoptosis and mitochondrial membrane potential using flow cytometric methods. Results: Total phenolic content and reducing power values were 11.9 mg gallic acid equivalents and 42.9 mg trolox equivalents per g sample, respectively. Ascorbic and gallic acid were detected in AMRE as major antioxidant compounds. We determined that AMRE increased cell cycle arrest at G(1) phase and exhibited apoptotic features via decreasing mitochondrial membrane potential in both prostate and lung cancer cells. Conclusion: These findings demonstrate that M. rubra extract can affect the behavior of human prostate and lung cancer cells in vitro conditions, and this effect now needs to be investigated in vivo.Öğe Phenolic Characterisation and Antioxidant Activity of Primula vulgaris and Its Antigenotoxic Effect on Fibroblast Cells(KOWSAR PUBL, 2017) Ozkan, Mehtap Tugce; Aliyazicioglu, Rezzan; Demir, Selim; Misir, Sema; Turan, Ibrahim; Yildirmis, Sermet; Aliyazicioglu, YukselBackground: Primula vulgaris has been used in traditional treatment, and its biological functions are attributed to its polyphenolics content. Objectives: The aim of this study was to determine the phenolics composition and the antioxidant activity of water extract of P. vulgaris (WEP) and to determine its probable preventive effects against H2O2-induced DNA damage in human fibroblast cells. Methods: The total polyphenolic content (TPC), ferric reducing antioxidant power (FRAP), and radical scavenging activity of WEP were determined using spectrophotometric methods. Phenolic compounds and antigenotoxic effects of WEP were evaluated using HPLC and comet assay, respectively. Results: The TPC and FRAP values of WEP were 15.023 +/- 0.84 mg gallic acid and 82.63 +/- 0.31 mu M trolox per g sample, respectively. rho-coumaric acid and rutin were detected as major phenolics. Moreover, WEP reduced H2O2-induced DNA damage in a concentration dependent manner in fibroblast cells compared to the positive controls (only 20 mu M H2O2 treatment). Conclusions: Primula vulgaris can be used in food, cosmetics, and drug industries because of its antioxidant and antigenotoxic activities.Öğe Selective Cytotoxic Effect of Dorycnium pentaphyllum Extract on Human Breast, Liver, and Lung Cancer Cells(KAHRAMANMARAS SUTCU IMAM UNIV REKTORLUGU, 2019) Demir, Selim; Turan, Ibrahim; Misir, Sema; Aliyazicioglu, YukselAlthough some studies have evaluated the cytotoxic activity of different Fabaceae species, there has been only limited research into the cytotoxic effect of Dorycnium pentaphyllum. The purpose of this study was to determine the antioxidant properties and cytotoxic effect of D. pentaphyllum extract on various human cancer cells. The total phenolic content (TPC) of the extract was determined using colorimetric method. The cytotoxic effect of the extract on human lung (A549), liver (HepG2), and breast (MCF-7) cancer cells and a normal human fibroblast cells was assessed using the MTT assay. TPC value of extract was found as 140.3 +/- 1.1 mg gallic acid equivalent per g sample. Extract showed selective cytotoxicity on all studied cancer cells compared to normal fibroblast cells, and the IC50 values of the extract in the cancer cells range from 100.4 to 298.5 mu g/mL. This is the first study to reveal the cytotoxic effect of D. pentaphyllum extract on cancer cell lines. Phytomedical applications of D. pentaphyllum may represent promising approaches in the treatment of cancer.