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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Treatment of renal cell carcinoma cell line A-498 with zebularine

ABSTRACT: Cultures of A-498 cells were treated for 120hours with 1000ÂµM zebularine (SIGMA) in three independent biological experiments. Zebularine acts as a DNA methyltransferase (DNMT) inhibitor thereby upregulating genes that are inactivated by e.g. promotor hypermethylation. The experiment aimed to search for upregulated transcripts to provide new targets for biomarker development and therapeutic use. 308 candidates were upregulated more than 1.5-fold. Members of the metallothionein group (MT1G, MT1H, and MT2A) were validated in 49 clinical samples of renal cell carcinomas. Total RNA of treated (1000ÂµM zebularine) and untreated A-498 cells (experiment A05-A07) was subjected to Affymetrix array analysis to detail the overall expression changes after treatment with a DNMT inhibitor. Treated cells showed no obvious signs of zebularine-induced cytotoxicity as revealed by XTT assays. Cell were split twice during the 120hour treatment period.

ORGANISM(S): Homo sapiens

SUBMITTER: Hans Krause

PROVIDER: E-GEOD-51627 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Treatment of prostate cancer cell lines DU-145 and LNCaP with zebularine

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2013-10-24 | E-GEOD-51629 | biostudies-arrayexpress

Treatment of renal cell carcinoma cell line A-498 with zebularine

Project description:Cultures of A-498 cells were treated for 120hours with 1000µM zebularine (SIGMA) in three independent biological experiments. Zebularine acts as a DNA methyltransferase (DNMT) inhibitor thereby upregulating genes that are inactivated by e.g. promotor hypermethylation. The experiment aimed to search for upregulated transcripts to provide new targets for biomarker development and therapeutic use. 308 candidates were upregulated more than 1.5-fold. Members of the metallothionein group (MT1G, MT1H, and MT2A) were validated in 49 clinical samples of renal cell carcinomas.

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2011-07-30 | E-GEOD-23991 | biostudies-arrayexpress

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2019-11-02 | E-MTAB-6832 | biostudies-arrayexpress

DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis.

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2013-12-01 | E-GEOD-42490 | biostudies-arrayexpress

Revealing the transitory and local effect of the demethylation agent zebularine on plant development and proteome dynamics of Salix purpurea

Project description:DNA methylation plays major roles in the epigenetic regulation of gene expression, transposon and transcriptional silencing, and DNA repair, with implications in developmental processes and phenotypic plasticity. Relevantly for arboreal species, DNA methylation constitute a regulative layer in cell wall dynamics associated with xylogenesis. The use of methyltransferase and/or demethylase inhibitors has been proven informative to shed light on the methylome dynamics behind the regulation of these processes. The present work employs the cytidine analog zebularine to inhibit DNA methyltransferases and induce DNA hypomethylation in Salix purpurea plantlets grown in vitro and in soil. An integrative approach has been adopted to highlight the effects of hypomethylation on proteomic dynamics, exposing the age-specific (three weeks of in vitro culture and one month of growth in soil) and tissue-specific (shoot and root) effects following exposure to zebularine. Significant proteomic shifts were revealed in the development from in vitro to in-soil culture and, whereas zebularine treatment decreased methylation in three-weeks roots, a functionally heterogeneous subset of protein entries was differentially accumulated in shoot samples, including entries associated with cell wall dynamics, tissue morphogenesis, and hormonal regulation. The identification of tissue-specific proteomic hallmarks in combination with hypomethylating agents provides new insights into the role of DNA methylation in early plant development in willow species.

2024-01-08 | PXD045653 | Pride

DNA Methyltransferase Inhibitor Zebularine Induces Human Cholangiocarcinoma Cell Death through Alteration of DNA Methylation Status

Project description:Cholangiocarcinoma (CCA) is a cancer arising from the neoplastic transformation of cholangiocytes. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. In this study, we explore the effect and possible mechanism of action of zebularine on CCA cells. We demonstrate that zebularine exerts an antitumor effect on CCA cells. Zebularine treatment decreased the concentrations of DNA methyltransferase (DNMT) proteins, and DNMT1 knockdown led to apoptotic cell death in the CCA cell lines TFK-1 and HuCCT1. DNA methylation analysis demonstrated that zebularine induced DNA demethylation, and the GO Biological Process terms “hemophilic cell adhesion”, “regulation of transcription, DNAdependent” and “Wnt signaling pathway” were found to be significantly enriched in association with demethylated genes. Furthermore, we observed that zebularine treatment decreased β-catenin protein levels in TFK-1 and HuCCT1 cells. These results suggest that zebularine alters DNA methylation status, and that some aspect of DNA demethylation by zebularine induces suppression of the Wnt signaling pathway, which leads to apoptotic cell death in CCA. We previously reported a novel mechanism of zebularine-induced cell growth arrest and apoptosis in hepatocellular carcinoma via a DNA methylation-independent pathway. Together, our present and previous studies indicate that zebularine could function as both a DNMT inhibitor and a non-DNMT inhibitor reagent, and that, while the optimal usage of zebularine may depend on cancer type, zebularine may be useful for chemotherapy against cancer.

2015-03-24 | GSE60446 | GEO

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