Browsing by Subject "apoptosis"
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Item Open Access 4,5-dianilinophtalimide protects neuroendocrine cells against serum deprivation-induced stress and apoptosis(2013) Ergin V.; Erdogan, M.; Karasu Ç.; Menevşe, A.OBJECTIVE: The aim of this study was to reveal the effects of 4,5-dianilinophthalimide (DAPH), which inhibits amyloid β fibrillization, against serum deprivation (SD)-induced apoptosis and the possible mechanisms in differentiated PC12 neuron cells. METHODS: Firstly, we evaluated whether DAPH protects cell viability exposed to SD by MTT assay. Next, we examined the changes of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73) and cleaved-CASP3 (Asp175) profiles by immunoblotting, in PC12 cells exposed to SD. Intracellular reactive oxygen species (ROS) level was also measured. RESULTS: SD induced apoptosis accompanied by up-regulation of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73), cleaved-CASP3 (Asp175) and intracellular ROS content. Co-treatment with nontoxic doses of DAPH prevented apoptosis by the attenuation of activated proteins and reduction of ROS level. These results suggest that serum deprivation-induced apoptosis inhibited by DAPH administration. CONCLUSION: We have provided for the first evidence that DAPH has a neuroprotective effect on SD-caused stress, probably via contributing the reestablishment of redox homeostasis. © 2013 Neuroendocrinology Letters.Item Open Access The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity(Nature Publishing Group, 2015) Sag, D.; Cekic, C.; Wu, R.; Linden J.; Hedrick, C.C.ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1-/- mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1-/- mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1-/- macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer. © 2015 Macmillan Publishers Limited. All rights reserved.Item Open Access Cytotoxic activities of some benzothiazole-piperazine derivatives(Taylor and Francis Ltd, 2015) Gurdal, E.E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Compound 1d is highly cytotoxic against all tested cancer cell lines. Further investigation of compound 1d by Hoechst Staining and Fluorescence-Activated Cell Sorting Analysis (FACS) revealed that this compound causes apoptosis by cell cycle arrest at subG1 phase. © 2014 Informa UK Ltd. All rights reserved.Item Open Access Herpes simplex virus 1 amplicon vector-mediated siRNA targeting epidermal growth factor receptor inhibits growth of human glioma cells in vivo(2005) Saydam O.; Glauser, D.L.; Heid I.; Turkeri G.; Hilbe, M.; Jacobs, A.H.; Ackermann, M.; Fraefel, C.In primary glioblastomas and other tumor types, the epidermal growth factor receptor (EGFR) is frequently observed with alterations, such as amplification, structural rearrangements, or overexpression of the gene, suggesting an important role in glial tumorigenesis and progression. In this study, we investigated whether posttranscriptional gene silencing by vector-mediated RNAi to inhibit EGFR expression can reduce the growth of cultured human gli36 glioma cells. To "knock down" EGFR expression, we have created HSV-1-based amplicons that contain the RNA polymerase III-dependent H1 promoter to express double-stranded hairpin RNA directed against EGFR at two different locations (pHSVsiEGFR I and pHSVsiEGFR II). We demonstrate that both pHSVsiEGFR I and pHSVsiEGFR II mediated knock-down of transiently transfected full-length EGFR or endogenous EGFR in a dose-dependent manner. The knock-down of EGFR resulted in the growth inhibition of human glioblastoma (gli36-luc) cells both in culture and in athymic mice in vivo. Cell cycle analysis and annexin V staining revealed that siRNA-mediated suppression of EGFR induced apoptosis. Overall HSV-1 amplicons can mediate efficient and specific posttranscriptional gene silencing. Copyright © The American Society of Gene Therapy.Item Open Access MAb 6D5 against proteins overexpressed in hepatocellular carcinoma cell lines(2007) Yagci, T.[No abstract available]Item Open Access Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes α7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons(2009) Hruska, M.; Keefe J.; Wert, D.; Tekinay, A.B.; Hulce J.J.; Ibañez-Tallon I.; Nishi, R.Vertebrate α-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases > 100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of α7-containing nicotinic acetylcholine receptors (α7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks α7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of α7 signaling-induced cell death during development. Copyright © 2009 Society for Neuroscience.Item Open Access A ranking-based meta-analysis reveals let-7 family as a meta-signature for grade classification in breast cancer(Public Library of Science, 2015) Oztemur, Y.; Bekmez, T.; Aydos, A.; Yulug I.G.; Bozkurt, B.; Dedeoglu, B.G.Breast cancer is one of the most important causes of cancer-related deaths worldwide in women. In addition to gene expression studies, the progressing work in the miRNA area including miRNA microarray studies, brings new aspects to the research on the cancer development and progression. Microarray technology has been widely used to find new biomarkers in research and many transcriptomic microarray studies are available in public databases. In this study, the breast cancer miRNA and mRNA microarray studies were collected according to the availability of their data and clinical information, and combined by a newly developed ranking-based meta-analysis approach to find out candidate miRNA biomarkers (meta-miRNAs) that classify breast cancers according to their grades and explain the relation between miRNAs and mRNAs. This approach provided meta-miRNAs specific to breast cancer grades, pointing out let-7 family members as grade classifiers. The qRTPCR studies performed with independent breast tumors confirmed the potential biomarker role of let-7 family members (meta-miRNAs). The concordance between the meta-mRNAs and miRNA target genes specific to tumor grade (common genes) supported the idea of mRNAs as miRNA targets. The pathway analysis results showed that most of the let-7 family miRNA targets, and also common genes, were significantly taking part in cancer-related pathways. The qRT-PCR studies, together with bioinformatic analyses, confirmed the results of meta-analysis approach, which is dynamic and allows combining datasets from different platforms. © 2015 Oztemur et al.Item Open Access Synthesis and anticancer activity evaluation of some benzothiazole-piperazine derivatives(Bentham Science Publishers B.V., 2015) Gurdal, E.E.; Buclulgan, E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Aroyl substituted compounds 1h and 1j were found to be the most active derivatives. In addition, further investigation of compounds 1h and 1j by Hoechst staining and FACS revealed that these compounds cause apoptosis by cell cycle arrest at subG1 phase. © 2015 Bentham Science Publishers.