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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.

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RNA expression in MDA-MB-231 cells treated for 24h with SAHA, Pargyline, or both [HG-U133A_2]

Drug Name:Pargyline;Suberoylanilide hydroxamic acid
Drug Category:HDMi;HDACi
Sample Type: human breast cancer cells (MDA-MB-231)
Condition:breast cancer
Experiment Type:Expression profiling by array
Experiment Platform:GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Description:In this study, we showed that treatment of human breast cancer cells with inhibitors targeting the zinc cofactor dependent class I/II HDACs, but not NAD+ dependent class III HDACs, led to significant increase of H3K4me2 which is a specific substrate of histone lysine-specific demethylase 1 (LSD1) and a key chromatin mark promoting transcriptional activation. We also demonstrated that inhibition of LSD1 activity by a pharmacological inhibitor, pargyline, or siRNA resulted in increased acetylation of H3K9 (AcH3K9). However, siRNA knockdown of LSD2, a homolog of LSD1, failed to alter the level of AcH3K9, suggesting that LSD2 activity may not be functionally connected with HDAC activity. Combined treatment with LSD1 and HDAC inhibitors resulted in enhanced levels of H3K4me2 and AcH3K9, and exhibited synergistic growth inhibition of breast cancer cells. Finally, microarray screening identified a unique subset of genes whose expression was significantly changed by combination treatment with inhibitors of LSD1 and HDAC. Our study suggests that LSD1 intimately interacts with histone deacetylases in human breast cancer cells. Inhibition of histone demethylation and deacetylation exhibits cooperation and synergy in regulating gene expression and growth inhibition, and may represent a promising and novel approach for epigenetic therapy of breast cancer.
PubmedID: 21452019
23354309
Citation:Huang Y; Vasilatos SN; Boric L;Shaw PG; Davidson NE.Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. Breast Cancer Res Treat 2012 Feb;131(3):777-89.
Vasilatos SN;Katz TA;Oesterreich S;Wan Y;Davidson NE;Huang Y. Crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells.Carcinogenesis 2013 Jun;34(6):1196-207.
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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.

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

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