ArticleCellular oncology (Dordrecht, Netherlands)2013
Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines.
Article in Cellular oncology (Dordrecht, Netherlands), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Aberrant gene promoter methylation of E-cadherin, p16Medical oncology (Northwood, London, England) · 2017Article
- DNA methylation profiling of primary neuroblastoma tumors using methyl-CpG-binding domain sequencing.Scientific data · 2016Article
- DNA methylation patterns in EBV-positive and EBV-negative Hodgkin lymphomas.Cellular oncology (Dordrecht, Netherlands) · 2015Article
- MYCN concurrence with SAHA-induced cell death in human neuroblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2015Article
- Age dependent changes in the LPS induced transcriptome of bovine dermal fibroblasts occurs without major changes in the methylome.BMC genomics · 2015Article
- Epigenome engineering in cancer: fairytale or a realistic path to the clinic?Frontiers in oncology · 2015Review
- Somatic mutations of amino acid metabolism-related genes in gastric and colorectal cancers and their regional heterogeneity--a short report.Cellular oncology (Dordrecht, Netherlands) · 2014Article
- Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents--implications for cancer treatment and chemoprevention.Cellular oncology (Dordrecht, Netherlands) · 2014Review
- Epigenetic contribution to individual variation in response to lipopolysaccharide in bovine dermal fibroblasts.Veterinary immunology and immunopathology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpigenetic alterations are inherent to cancer cells, and epigenetic drugs are currently primarily used to treat hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and also exhibit epigenetic alterations involving e.g. apoptotic pathways, which suggests that these tumors may also be sensitive to epigenetic drugs. This notion prompted us to assess molecular and functional effects of low dosage epigenetic drugs in neuro-ectodermal tumor-derived cell lines of pediatric origin.
resultsIn 17 neuroblastoma (NBL) and 5 peripheral primitive neuro-ectodermal tumor (PNET) cell lines a combination treatment of 5-aza-2'-deoxycytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages was found to reduce proliferation and to induce wide-spread DNA demethylation, accompanied by major changes in gene expression profiles. Approximately half of the genes that were significantly up-regulated upon treatment exhibited a significant demethylation in their promoter regions. In the NBL cell lines, almost every cellular pathway (193/200) investigated showed expression alterations after treatment, especially a marked up-regulation of genes in the p53 pathway. The combination treatment also resulted in up-regulation of known epigenetically regulated genes such as X-chromosomal genes, tissue-specific genes and a limited number of imprinted genes, as well as known tumor suppressor genes and oncogenes.
conclusionsNanomolar dosages of epigenetic drugs have a dramatic impact on the genomes of neuro-ectodermal tumor-derived cell lines, including alterations in DNA methylation and concomitant alterations in gene expression.
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