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Öğe Association of Cytotoxic T Lymphocyte Antigen-4 Gene Polymorphisms with Psoriasis Vulgaris: A Case-Control Study in Turkish Population(Hindawi Ltd, 2018) Dursun, Hatice Gul; Yilmaz, Huseyin Osman; Dursun, Recep; Kulaksizoglu, SevsenPsoriasis is a common, chronic, and autoimmune skin disease in which dysregulation of immune cells, particularly T cells, is thought to play an important role in the pathogenesis. Cytotoxic T lymphocyte antigen-4 (CTLA-4) expressed only on activated T cells is an immunoregulatory molecule and plays a role in the pathogenesis of autoimmune disorders. We aimed to determine whether CTLA-4 gene polymorphisms are associated with development and/or clinical features of psoriasis vulgaris (Pv). Genotyping of SNPs (-318C>T, +49A>G, and CT60A>G) in CTLA-4 gene was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 103 Pv patients and 102 controls. No statistically significant associations were detected in any of the investigated genetic models for the -318C>T polymorphism. The genotype distributions of +49A>G and CT60A>G were associated with Pv development. In haplotype analysis, while frequency of CAA haplotype was significantly higher in the control group, frequencies of CGG and CAG haplotype were significantly higher among the patients. However, all of CTLA-4 polymorphisms and haplotypes do not have an effect on severity and onset age of Pv. In conclusion, the +49A>G and CT60A>G polymorphisms may be risk factors for Pv development. Furthermore, CGG and CAG haplotypes may contribute to Pv development, while CAA haplotype may be protective against Pv.Öğe Bioactive Compounds of Rheum ribes L. and its Anticancerogenic Effect via Induction of Apoptosis and miR-200 Family Expression in Human Colorectal Cancer Cells(Routledge Journals, Taylor & Francis Ltd, 2021) Ayan, Ilknur Cnar; Cetinkaya, Sumeyra; Dursun, Hatice Gul; Suntar, IpekRheum ribes L. is a widespread plant species in the eastern part of our country and is consumed as a vegateble by the folk people. In our study, we investigated whether R. ribeshas anti-cancerogenic effect on colorectal cancer cell lines. Six different extracts were obtained from R. ribes. Total phenolic, flavonoid contents, antioxidant activities, and cytotoxic effects of all extracts on colorectal cancer cells were determined. Differences in expression levels of the miR-200 family and target genes were assessed by real-time qPCR in cells. Antiproliferative effect was determined by TUNEL, Annexin V, cell cycle, invasion analysis; and levels of BCL-2, ZEB1, GATA4 and FAS/CD95 proteins were determined by ELISA. According to the results of miRNA expression analysis, the only dose group with a significant increase (p < 0,05) in the expression level of all of miRNAs in both cell lines was RM (Root methanol) extract alone. Our results showed that, RM caused a significant increase in the expressions of miR-200a/b/c and miR-141, and it suppressed BCL-2, ZEB1, GATA4 expressions, with this way. Thus, it has been suggested that the treatment of RM alone, or combined treatment of RM with 5-FU result in a better response than cancer cells treated with 5-FU alone.Öğe Evaluation of Apoptosis Pathway of Geraniol on Ishikawa Cells(Routledge Journals, Taylor & Francis Ltd, 2021) Kuzu, Betul; Cuce, Gokhan; Ayan, Ilknur Cinar; Gultekin, Burcu; Canbaz, Halime Tuba; Dursun, Hatice Gul; Sahin, ZaferEndometrial cancer is the most common type of cancer in the female reproductive system. Geraniol is acyclic monoterpene alcohol derived from essential oils of aromatic plants. This study aimed to investigate the apoptosis pathway of geraniol on Ishikawa cells. The cytotoxic effects of Geraniol on Ishikawa cells were determined by an MTT test. Ishikawa cells were seeded on cover slips, the IC50 dose was applied, and the cells were incubated with antibodies against Bax, Bcl-2, and TUNEL Assay. mRNA expression analysis of apoptosis-related genes was determined by RT-qPCR with an IC50 dose of Geraniol. The IC50 dose of Geraniol decreased Bcl-2 staining significantly, but it significantly increased Bax staining and TUNEL positive cells. A significant increase in the Bax, caspase3, caspase-8, cytochrome C and Fas genes and a significant decrease in the Bcl-2 gene was observed when the IC50 dose group was compared to the cells in the control group based on their mRNA expression levels.Analysis of expression of genes whose products are involved in apoptosis suggests the involvement of the mitochondrial pathway.Öğe NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris(Hindawi Ltd, 2018) Dursun, Recep; Dursun, Hatice Gul; Zamani, Ayse Gul; Yildirim, Mahmut Selman; Cinar, ElknurPsoriasis is a common, chronic, and autoimmune skin disease. Factors that play a role in etiopathogenesis of psoriasis include internal factors such as genetic susceptibility and immunological factors and external factors such as stress, infection, trauma, drug, and environmental compounds. N-acetyltransferase 2 ( NAT2) is a xenobiotic enzyme that is involved in the metabolism of drugs, environmental toxins, and carcinogens. In this study, we aimed to demonstrate whether the variations in the NAT2 gene lead to a predisposition to psoriasis by affecting the enzyme's ability to metabolize drugs and environmental components or not. Three polymorphisms (rs1799929, rs1799930, and rs1799931) in NAT2 gene were genotyped and compared by real-time PCR method in 260 psoriasis vulgaris patients and 200 healthy controls. There was no difference in the genotype distributions and allele frequencies of polymorphisms between psoriasis vulgaris patients and controls. When the effects of polymorphisms on the clinical features of the disease, such as onset age and severity, are assessed, it has been found that rs1799930 and rs1799929 are, respectively, associated with early onset age and severity of the disease. In conclusion, rs1799929, rs1799930, and rs1799931 polymorphisms of the NAT-2 gene do not appear to be a risk factor for the development of psoriasis. Conversely, they may have an effect on either more severe or early onset cases of the disease.Öğe The Phytochemical Profile and Biological Activity of Liquidambar orientalis Mill. var. orientalis via NF-?B and Apoptotic Pathways in Human Colorectal Cancer(Routledge Journals, Taylor & Francis Ltd, 2022) Cetinkaya, Sumeyra; Cinar Ayan, Ilknur; Suntar, Ipek; Dursun, Hatice GulLiquidambar orientalis Mill. var. orientalis (Hammamelidaceae) commonly known as oriental sweet gum is a medicinal plant endemic to Turkey, and used for treatment of wounds such as ulcers, gastritis and skin diseases. However, there are only a limited number of studies on the anticancer properties of this plant. The aim of this study is to investigate the cellular and molecular mechanisms of L. orientalis in colorectal cancer cell lines and to reveal the active therapeutic components. Antioxidant, anti-proliferative, anti-invasive and apoptotic effects were investigated for determining biological activities. The phytochemical profile and quantitation assays were carried out by using HPLC-ESI-Q-TOF-MS. The results demonstrated that leaf methanol extract (LM) of L. orientalis has the highest cytotoxic activity in HCT-116 (IC50 27.80 mu g/mL) and HT-29 (IC50 43.13 mu g/mL) cell lines as compared to the other extracts tested. Regarding chemical composition, quercetin 3-glucoside (61.005 +/- 1.527 mg/g extract), chlorogenic acid (31.627 +/- 0.970 mg/g extract), pyrogallol (9.950 +/- 0.001 mg/g extract), epigallocatechin gallate (9.671 +/- 0.004 mg/g extract), apigenin 7-O-glucoside (2.687 +/- 0.027 mg/g extract), gallic acid (2.137 +/- 0.012 mg/g extract), genistin (1.270 +/- 0.027 mg/g extract), luteolin (0.055 +/- 0.0005 mg/g extract) and kaempferol (0.506 +/- 0.007 mg/g extract) were identified as the major phytochemical compounds. Our results showed that LM extract exhibited In Vitro cytotoxic and apoptotic properties.Öğe Piceatannol induces apoptotic cell death through activation of caspase-dependent pathway and upregulation of ROS-mediated mitochondrial dysfunction in pancreatic cancer cells(Springer, 2022) Ayan, Ilknur Cinar; Guclu, Ebru; Vural, Hasibe; Dursun, Hatice GulBackground Piceatannol is a naturally occurring plant-derived phenolic compound (stilbenoid), an analogue of resveratrol. It has been shown that, piceatannol has biological activity properties such as antiproliferative, antioxidative, anti-inflammatory and proapoptotic, in various human cancer studies in vitro and in vivo. Objectives and methods In this study, it was aimed to investigate whether piceatannol induces apoptosis through anticancer activity methods (cell viability, colony formation, annexin-V/7-AAD, ROS (Reactive oxygen species), MMP (Mitochondrial membrane potential), wound healing, invasion assay, RT-qPCR (Real-Time Quantitative Polymerase Chain Reaction), western blotting in PANC-1 and MIA PaCa-2 pancreatic cancer (PC) cell lines. Results According to our results, piceatannol decreased cell viability in a dose and time-dependent manner [the half-maximal inhibitory concentration (IC50): 60 mu M in PANC-1 and IC50: 90 mu M in MIA PaCa-2 cell line at 48 h (h)] and caused significant changes in the expression of apoptosis-related genes and protein. Piceatannol induced apoptosis in PANC-1 and MIA PaCa-2 cells, accompanied by increased ROS production, decreased MMP, and increased Caspase-3-9 activity. Piceatannol also inhibited colony-forming abilities, invasion, and migration of PC cells. Conclusion Our results show that piceatannol has an anti-cancerogenic effect on PANC-1 and MIA PaCa-2 cells, and exerts this effect by suppressing proliferation and inducing apoptosis. Therefore, piceatannol could be considered to be a potential chemotherapeutic agent candidate for the treatment and prevention of PC. [GRAPHICS] .
