Person: YERLİKAYA, PINAR OBAKAN
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YERLİKAYA
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PINAR OBAKAN
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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 Open Access Aging-related diseases and autophagy(2016) Çoker Gürkan , Ajda; Palavan Unsal, Narcin; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKANAutophagy is fundamental, evolutionary conserved physiological process at molecular level which targets long-lived cytosolic proteins and organelles to be recycled through lysosomal degradation. Diminished autophagic activity caused cellular stress in many organisms following aging, and inhibition of autophagy in model organisms causes degenerative changes and pathologic diseases observed with high incidence ratio generally in older ages. Consequently the delayed senescence or increased longevity in model organisms often stimulate autophagy, and autophagy inhibition compromises anti-aging effects. The cytoprotective function of autophagy is presented in various human diseases such as lung, liver, cardiovascular diseases, neurodegeneration, myopathies, cancer, stroke, infections and metabolic diseases which are found associated with autophagic targets. These pathologies are defined with their age-dependent characteristics, is not fully understood that how autophagy network regulates metabolism and may cause diseases in age-related manner. In this book chapter, we are going to discuss the autophagy and aging relationship in three different parts. In the first section autophagy and aging relationship is going to be presented through explaining responsible signalling network. The autophagy and age-related neurological disorders, genetic basis of age-dependent diseases and the functional role of autophagy is going to be discussed in the second and third part of the chapter.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 Activation of polyamine catabolic enzymes involved in diverse responses against epibrassinolide-induced apoptosis in LNCaP and DU145 prostate cancer cell lines(Springer Wien, Sachsenplatz 4-6, Po Box 89, A-1201 Wien, Austria, 2014-03) Palavan Unsal, Narçin; Calcabrini, Annarica; Agostinelli, Enzo; Bolkent, Şehnaz; ARISAN, ELİF DAMLA; YERLİKAYA, PINAR OBAKAN; 156421; 113920; 6125; 3894Epibrassinolide (EBR) is a biologically active compound of the brassinosteroids, steroid-derived plant growth regulator family. Generally, brassinosteroids are known for their cell expansion and cell division-promoting roles. Recently, EBR was shown as a potential apoptotic inducer in various cancer cells without affecting the non-tumor cell growth. Androgen signaling controls cell proliferation through the interaction with the androgen receptor (AR) in the prostate gland. Initially, the development of prostate cancer is driven by androgens. However, in later stages, a progress to the androgen-independent stage is observed, resulting in metastatic prostate cancer. The androgen-responsive or -irresponsive cells are responsible for tumor heterogeneity, which is an obstacle to effective anti-cancer therapy. Polyamines are amine-derived organic compounds, known for their role in abnormal cell proliferation as well as during malignant transformation. Polyamine catabolism-targeting agents are being investigated against human cancers. Many chemotherapeutic agents including polyamine analogs have been demonstrated to induce polyamine catabolism that depletes polyamine levels and causes apoptosis in tumor models. In our study, we aimed to investigate the mechanism of apoptotic cell death induced by EBR, related with polyamine biosynthetic and catabolic pathways in LNCaP (AR+), DU145 (AR-) prostate cancer cell lines and PNT1a normal prostate epithelial cell line. Induction of apoptotic cell death was observed in prostate cancer cell lines after EBR treatment. In addition, EBR induced the decrease of intracellular polyamine levels, accompanied by a significant ornithine decarboxylase (ODC) down-regulation in each prostate cancer cell and also modulated ODC antizyme and antizyme inhibitor expression levels only in LNCaP cells. Catabolic enzymes SSAT and PAO expression levels were up-regulated in both cell lines; however, the specific SSAT and PAO siRNA treatments prevented the EBR-induced apoptosis only in LNCaP (AR+) cells. In a similar way, MDL 72,527, the specific PAO and SMO inhibitor, co-treatment with EBR during 24 h, reduced the formation of cleaved fragments of PARP in LNCaP (AR+) cells.Publication Metadata only Triptolide overcome autocrine Growth Hormone (GH) Mediated Resistance in a Dose-Dependent Manner in MDA-MB-453 Breast Cancer Cells Via Acting on EMT Pathway(2019-07-06) Malcanlı, S; Ozkurt, E.; Palavan Unsal, N.; Coker Gürkan, A.; ŞAHİN, BURCU AYHAN; YERLİKAYA, PINAR OBAKAN; ARISAN, ELİF DAMLA; 30985Breast cancer is one o f the most common cancer types among women. Beyond environmental and genetic risk factors such as age and genetic background, many growth factors (e.g. VEGF) and hormones (estrogen) are known to affect the development o f breast cancer. Recently, autocrine growth hormone (GH), an essential hormone affecting post-natal growth, has been shown to trigger cell proliferation, invasion, metastasis, and also lead to drag resistance. Upregulation of GH and its receptor (GHR) expression was determined in mammary carcinoma cells. Forced GH expression induced drag resistance against tamoxifen, doxorubicin, mitomycin and curcumin in MCF-7, T47D and BT^I74 breast cancer cells. Triptolide is a diterpenoid triepoxide which have been demonstrated to have multiple biological activities and also triggers apoptotic cell death in breast cancer cells. In this study, our aim was to investigate the role of epithelial-mesenchymal transition (EMT) signalling during triptolide-induccd apoptotic cell death in MDA-MB-453 wt and GH+ breast cancer cells. Triptolide decreased cell viability in a dose-dependent manner, mitochondrial membrane potential loss and nuclear fragmentation were observed. 20 nM triptolide decreased cell viability by 25% and 15% in MDA-MB-453 wt and GH+ cells, respectively. Although autocrine GH expression triggered cell proliferation and colony formation in MDA-MB-453 cells, triptolide (20 nM) treatment suppressed forced GH-mediated invasion and metastasis. Furthermore, autocrine GH mediated aggressive profile was prevented by triprolide treatment through Slug, N-cadherin, Vimentin downregulation within 24 h. Triptolid induced caspase-dependent apoptotic cell death via modulating Bcl-2 family member's expression profile in MDA-MB-453. In consequence, autocrine GH overexpression increased aggressive phenotype of MDA-MD-453 breast cancer cells, however triptolide treatment overcame this resistance mechanism and induced apoptotic cell death.Publication Restricted The Role of the PI3K/AKT/mTOR Signaling Axis in the Decision of the Celastrol-Induced Cell Death Mechanism Related to the Lipid Regulatory Pathway in Prostate Cancer Cells(Elsevier, 2020) RENCÜZOĞULLARI, ÖZGE; Çoban, Mervenur; Sevgin, Bortecine; Çoker-Gürkan, Ajda; YERLİKAYA, PINAR OBAKAN; Palavan-Ünsal, Narcin; ARISAN, ELİF DAMLAProstate cancer is one of the leading cancer types among the male population worldwide, with high incidence and mortality rates. Celastrol is a promising bioactive component extracted from Tripterygium wilfordi. Celastrol is a multimodal agent with therapeutic advantages, with activities that affect cell proliferation, inflammation (through affecting proteotoxic stress) and cell death mechanisms such as autophagy, apoptosis and paraptosis. Celastrol alters the PI3K/AKT signaling axis to suppress the cell viability of cancer cells. Although a number of celastrol targets have been identified in cancer cells, the genomic differences in malignant cells prevent the efficacy of celastrol. Therefore, new studies are required to highlight its potential therapeutic effects in cancer cells. In this study, we investigated the therapeutic potential of celastrol in LNCaP, DU145 and PC3 prostate cancer cells. According to our results, celastrol decreased cell viability in a dose-dependent manner in the cells. LNCaP prostate cancer cells were more sensitive to celastrol treatment compared to DU145 and PC3 cells. We found that celastrol modulated PI3K/AKT/mTOR signaling to alter lipid regulatory pathways by affecting LAMP -1 and lipin-1 in PC3 cells. Although celastrol downregulated FASN in all cell lines, active mTOR signaling led to altered responses in prostate cancer cells by affecting the cellular fate decision pathways.Publication 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; 6125