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Publication Metadata only The potential role of polyamine metabolism in different growth hormone mutations (E33G, N47D, T-24A, A13S, W-7X, IVS1GAAA, IVS183C-1, F166Del) on Epithelial mesenchymal transition (EMT) in HEK293(2016) Kaysın, Furkan; Çoker Gürkan, Ajda; Ünsal, Zeynep Narçin; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 125860; 113920; 156421; 6125Publication Metadata only Lack of evidence for the association of ornithine decarboxylase (+316 G>A), spermidine/spermine acetyl transferase (‑1415 T>C) gene polymorphisms with calcium oxalate stone disease(2013) Çoker Gürkan, Ajda; Arısan, Serdar; Ünsal, Zeynep Narçin; ARISAN, ELİF DAMLA; 125860; 113920; 6125Urolithiasis is a complex and multifactorial disorder characterized by the presence of stones in the urinary tract. Urea cycle is an important process involved in disease progression. L‑ornithine is a key amino acid in the urea cycle and is converted to putrescine by ornithine decarboxylase (ODC). Putrescine, spermidine and spermine are natural polyamines that are catabolized by a specific enzyme, spermidine/spermine acetyltransferase (SSAT). The single‑nucleotide polymorphisms (SNPs) in the intron region of ODC (+316 G>A) and promoter region of SSAT (‑1415 T>C) genes have been found to be associated with the polyamines expression levels. The aim of this study was to examine whether the ODC (+316 G>A) intron 1 region gene polymorphism and SAT‑1 promoter region (‑1415 T>C) gene polymorphisms are potential genetic markers for susceptibility to urolithiasis. A control group of 104 healthy subjects and a group of 65 patients with recurrent idiopathic calcium oxalate stone disease were enrolled into this study. Polymerase chain reaction (PCR)‑based restriction analysis was performed for the ODC intron 1 (+316 G>A) region and SAT‑1 (‑1415 T>C) promoter gene polymorphisms by PstI and MspI restriction enzyme digestion, respectively. The genotype distribution of polymorphisms studied in the ODC intron 1 region (+316 G>A) and SAT‑1 ‑1415 T>C promoter region did not reveal a significant difference between urolithiasis and the control groups (P=0.713 and 0.853), respectively. Furthermore, no significant difference was observed between the control and patient groups for ODC +316 G>A and SAT‑1 ‑1415 T>C allele frequencies (P=0.877 and 0.644), respectively. In conclusion, results of the present study suggest that ODC + 316 G>A and SAT‑1 ‑1415 T>C gene polymorphisms might not be a risk factor for urolithiasis.Publication Metadata only The inhibition of PI3K and NF kappa B promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells(Elsevier France-Editions Scientifiques Medicales Elsevier, 23 Rue Linois, 75724 Paris, France, 2016-02) Akkoç, Yunus; Çoker Gürkan, Ajda; Palavan Ünsal, Zeynep Narçın; Berrak, Özge; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 113920; 125860; 156421; 6125Bcl-2 protein has been contributed with number of genes which are involved in oncogenesis. Among the many targets of Bcl-2, NF kappa B have potential role in induction of cell cycle arrest. Curcumin has potential therapeutic effects against breast cancer through multiple signaling pathways. In this study, we investigated the role of curcumin in induction of cell cycle arrest via regulating of NF kappa B and polyamine biosynthesis in wt and Bcl-2+ MCF-7 cells. To examine the effect of curcumin on cell cycle regulatory proteins, PI3K/Akt, NF kappa B pathways and polyamine catabolism, we performed immunoblotting assay. In addition, cell cycle analysis was performed by flow cytometry. The results indicated that curcumin induced cell cycle arrest at G2/M phase by downregulation of cyclin B1 and Cdc2 and inhibited colony formation in MCF-7 wt cells. However, Bcl-2 overexpression prevented the inhibition of cell cycle associated proteins after curcumin treatment. The combination of LY294002, PI3K inhibitor, and curcumin induced cell cycle arrest by decreasing CDK4, CDK2 and cyclin E2 in Bcl-2+ MCF-7 cells. Moreover, LY294002 further inhibited the phosphorylation of Akt in Bcl-2+ MCF-7 cells. Curcumin could suppress the nuclear transport of NF kappa B through decreasing the interaction of P-I kappa B-NF kappa B. The combination of wedelolactone, NF kappa B inhibitor, and curcumin acted different on SSAT expression in wt MCF-7 and Bcl-2+ MCF-7 cells. NF kappa B inhibition increased the SSAT after curcumin treatment in Bcl2 overexpressed MCF-7 cells. Inhibition of NF kappa B activity as well as suppression of ROS generation with NAC resulted in the partial relief of cells from G2/M checkpoint after curcumin treatment in wt MCF7 cells. In conclusion, the potential role of curcumin in induction of cell cycle arrest is related with NF kappa B-regulated polyamine biosynthesis. (C) 2015 Elsevier Masson SAS. All rights reserved.Publication Metadata only ODC is a Mediator of the Purvalanol A-Induced Apoptotic Signaling via the p38 Mitogen-Activated Protein Kinase Pathway in MCF-7 Breast Cancer Cells(2012) Köse, Betsi; Alkurt, Gizem; Çoker Gürkan, Ajda; Ünsal, Zeynep Narçin; ARISAN, ELİF DAMLA; 125860; 113920; 6125Publication Open Access Celastrol Modulates Lipid Synthesis via PI3K/Akt/mTOR Signaling Axis to finalize Cell Death Response in Prostate Cancer Cells(2017) Çoker Gürkan, Ajda; Ünsal, Zeynep Narçin; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; RENCÜZOĞULLARI, ÖZGE; 113920; 222563; 125860; 156421; 6125FASN is key enzyme during lipid biogenesis is associated with prostate cancer. In this study, we aim to investigate the potential role of celastrol, root extracts of Tripterygium wilfordii on modulation of lipid biosynthesis-associated PI3K/Akt signaling. To determine the effect of celastrol on cell viability, prostate cancer cells were exposed with celastrol in dose dependent manner. AR (+) LNCaP and AR (−) DU145 and PC3 cell viability were inhibited by celastrol with IC50 in the range of 0.05–1 µM. To address the role of celastrol on cell death mechanism, celastrol-treated prostate cancer cells were evaluated with immunoblotting and flow cytometric analysis. Celastrol significantly upregulated PARP and caspase 9 cleavage also increased sub-G1 population. Celastrol also inhibited cell migration and invasion. These effects were associated with decreased PI3K/Akt signaling axis and downregulation of epithelial mesenchymal transition in prostate cancer cells. Likewise, lipid biosynthesis was downregulated with celastrol, however inhibition of PI3K/Akt signaling axis via LY294002 further decrease the cell migration and proliferation rate in prostate cancer cells. Our data suggest that, celastrol suppressed cell proliferation via inhibition of lipid biosynthesis through downregulation of PI3K/Akt signal axis. Targeting lipid metabolism-related enzymes in prostate cancer may offer new avenues for therapeutic approaches.Publication Metadata only ER stress is involved in Epibrassinolide-induced apoptotic cell death(2014) Çoker Gürkan, Ajda; Ünsal, Zeynep Narçin; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 156421; 113920; 125860; 6125Publication Metadata only Growth hormone mediated resistance against curcumin induced-apoptosis via modulating of JAK/STAT/SOCS pathway and inflammatory cytokines in MDA-MB-453 breast cancer cells(Wiley-Blackwell, 111 River St, Hoboken 07030-5774, NJ USA, 2016-09) Uğur, M.; Çoker Gürkan, Ajda; Palavan Ünsal, Zeynep Narçın; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 125860; 113920; 156421; 6125Publication Metadata only Purvalanol and roscovitine exert their apoptotic effect differently in terms of mTOR downstream signalling route(2015) Doğruel, Tuğçe; Berrak, Özge; Çoker Gürkan, Ajda; Ünsal, Zeynep Narçin; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 113920; 156421; 125860; 6125Publication Metadata only Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells(Elsevier France-Editions Scientifiques Medicales Elsevier, 23 Rue Linois, 75724 Paris, France, 2015-04) Akkoç, Yunus; Berrak, Özge; Çoker Gürkan, Ajda; Palavan Ünsal, Zeynep Narçın; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 113920; 156421; 125860; 6125Curcumin is a natural anti-cancer agent derived from turmeric (Curcuma longa). Curcumin triggers intrinsic apoptotic cell death by activating mitochondrial permeabilization due to the altered expression of pro-and anti-apoptotic Bcl-2 family members. Phosphoinositol-3-kinase (PI3K) and Akt, key molecular players in the survival mechanism, have been shown to be associated with the Bcl-2 signaling cascade; therefore, evaluating the therapeutic efficiency of drugs that target both survival and the apoptosis mechanism has gained importance in cancer therapy. We found that Bcl-2 overexpression is a limiting factor for curcumin-induced apoptosis in highly metastatic MCF-7 breast cancer cells. Forced overexpression of Bcl-2 also blocked curcumin-induced autophagy in MCF-7 cells, through its inhibitory interactions with Beclin-1. Pre-treatment of PI3K inhibitor LY294002 enhanced curcumin-induced cell death, apoptosis, and autophagy via modulating the expression of Bcl-2 family members and autophagosome formation in MCF-7 breast cancer cells. Atg7 silencing further increased apoptotic potential of curcumin in the presence or absence of LY294002 in wt and Bcl-2+ MCF-7 cells. The findings of this study support the hypothesis that blocking the PI3K/Akt pathway may further increased curcumin-induced apoptosis and overcome forced Bcl-2 expression level mediated autophagic responses against curcumin treatment in MCF-7 cells. (C) 2015 Elsevier Masson SAS. All rights reserved.Publication Embargo Epibrassinolide-induced apoptosis regardless of p53 expression via activating polyamine catabolic machinery, a common target for androgen sensitive and insensitive prostate cancer cells(Wiley-Blackwell, 111 River St, Hoboken 07030-5774, Nj Usa, 2014-12) Çoker Gürkan, Ajda; Palavan Unsal, Narçin; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 156421; 113920; 125860; 6125BACKGROUNDEpibrassinolide (EBR), is a member of the brassinosteroids (BR), has been shown as an apoptotic inducer in different cancer cell lines. We previously showed that EBR induced apoptosis by activating polyamine catabolic pathway, which lead to the accumulation of cytotoxic compounds such as hydrogen peroxide and aldehydes in LNCaP and DU 145 prostate cancer cells. However, we found that LNCaP prostate cancer cells expressing functional androgen receptor (AR) was found more sensitive to EBR than those with non-functional AR (DU 145 cells). RESULTSTo better understand the apoptotic effect of EBR, we aimed to investigate the cellular responses in p53 null, PC3 prostate cancer cells. We showed that EBR induced mitochondria-mediated and caspase-dependent apoptosis in wt and p53 stable transfected PC3 cells, which suggesting that EBR-induced apoptosis regardless of p53 expression. In addition, inhibition of p53 by pifithrin- orthe activation of Mdm2 by Nutlin-3 co-treatment did not alter EBR induced PARP cleavage. Furthermore, EBR treatment was also induced apoptosis in both LNCaP(wt p53) and DU 145 (mt p53)cells, respectively. These all findings verified that EBR-induced apoptosis regardless of p53 expression. The PA catabolic pathway was also altered in PC3 cells causing the generation of reactive oxygen species (ROS) and intracellular PA pool decrease. However, the silencing of spermidine-spermineacetyltransferase (SSAT), a key enzyme at polyamine catabolic machinery prevented the EBR-induced apoptosis. CONCLUSIONSTherefore, we concluded that EBR-induced apoptosis was mainly related with PA catabolic pathway and independent from p53 expression. Prostate 74: 1622-1633, 2014. (c) 2014 Wiley Periodicals, Inc.