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

Romidepsin and azacitidine synergize in their epigenetic modulatory effects to induce apoptosis in CTCL

Drug Name:romidepsin
Drug Category:HDACi
Sample Type:CTCL cell lines as well as CD4+ T cells derived from patients with Sézary Syndrome (SS) with high tumor burden
Condition:CTCL ,Sézary Syndrome (SS)
Experiment Type:Methylation profiling by high throughput sequencing
Experiment Platform:GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Description:PURPOSE:Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies that despite available therapies commonly relapse. The emergence of combination epigenetic therapies in other hematologic malignancies have made investigation of such combinations in CTCL a priority. Here, we explore the synergistic antiproliferative effects of romidepsin, an HDAC inhibitor, and azacitidine, a demethylating agent, combination in CTCL. EXPERIMENTAL DESIGN: The growth inhibition under combination treatment and single agent was explored by the MTT cell viability assay and the Annexin V/propidium iodide (PI) apoptosis assay in different CTCL cell lines and tumor cells derived from Sézary syndrome patients. Quantitative analysis of a dose-effect relationship of romidepsin and azacitidine was done by the CompuSyn software. Investigation of mechanism of action was performed by flow cytometry, immunoblotting, qRT-PCR arrays, and chromatin immunoprecipitation. Global CpG methylation sequencing was utilized to study genome methylation alteration under the treatment modalities. RESULTS: The combination of romidepsin and azacitidine exerts synergistic antiproliferative effects and induction of apoptosis involving activation of the caspase cascade in CTCL cell lines and tumor cells derived from Sézary syndrome patients. We identified genes that were selectively induced by the combination treatment, such as the tumor suppressor geneRhoBthat is linked to enhanced histone acetylation at its promoter region in parallel with pronounced expression of p21. Global CpG methylation sequencing in a CTCL cell line and tumor cells demonstrated a subset of genes with a unique change in methylation profile in the combination treatment. CONCLUSIONS: The synergistic antiproliferative effects of romidepsin and azacitidine combination treatment justify further exploration in clinical trials for advanced CTCL.Clin Cancer Res; 22(8); 2020-31.
PubmedID:26660520
Citation:Rozati S; Cheng PF;Widmer DS;Fujii K; Levesque MP;Dummer R. Romidepsin and Azacitidine Synergize in their Epigenetic Modulatory Effects to Induce Apoptosis in CTCL. Clin Cancer Res 2016 Apr 15;22(8):2020-31.
Downlaod:File Download (123.555MB)

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