Welcome to HEDD

The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on the storage and integration of epigenetic drug datasets that were obtained from laboratory experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

read more

Combination of HDAC inhibitors and Azacytidine for Cancer Cell Selective Targeting of Esophageal Cancer Cells

Drug Name:5-Azacytidine;Entinostat
Drug Category:DNMTi;HDACi
Sample Type:human esophageal tumor cell lines (OE21 and OE33);human non-neoplastic esophageal epithelial cells (Het1A cells)
Condition:esophageal tumor,non-neoplastic esophageal epithelial
Experiment Type:Expression profiling by array
Experiment Platform:GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Description:Esophageal cancers (ECs) are highly aggressive tumors with poor prognosis and few treatment options. This study investigated the possibility of treating esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells by inhibitors of broad and specific histone deacetylases (HDACi; SAHA, MS-275, FK228) and/or of DNMT (Azacytidine, AZA). Drug targets (HDAC1,2,3 and DNMT1) were present in non-neoplastic (HET-1A), ESCC (OE21) and EAC (OE33) cell lines. All cell lines responded to HDACi by reduced HDAC activity and increased histone acetylation as well as to AZA by up-regulation of p21. Expression of drug targets remained largely unaffected by HDACi and AZA treatment. Importantly, cell viability, apoptosis, cell cycle dynamics and DNA damage were only affected by HDACi and/or AZA in ESCC and EAC, but not the non-neoplastic cells. This was specifically seen for the combination of MS-275 and AZA, leading to enhanced cancer cell selectivity and drug efficiency. By transcriptome analyses of MS-275, AZA and MS-275/AZA treated cells, known (e.g. p21) as well as novel regulated genes significantly associated with the cellular effects post HDACi and/or AZA treatment in ESCC and EAC cells were identified. Finally, human EC tissue specimens frequently expressed the actionable drug targets HDAC1/2/3 and DNMT1. In summary, a combined HDACi (MS-275)/AZA treatment is cancer cell selective and efficient in vitro. Since the majority of ECs express the drug targets in situ, this paves the way for further investigations of HDACi/AZA treatment in esophageal cancer cells and their translation into a clinico-pathological setting.
PubmedID:25923331
Citation:Ahrens TD;Timme S; Hoeppner J;Ostendorp J; Hembach S; Follo M; Hopt UT; Werner M; Busch H; Boerries M;Lassmann S.Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine.Epigenetics 2015;10(5):431-45
Downlaod:File Download (26.172MB)

About

pix

The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on integrating epigenetic drug studies based Omics data from high through experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

Copyright

©2016 Group of Computational Epigenomics and Bioinformatics, College of Life Science, Jilin Normal University, China

吉ICP备16005872号