Improved Therapeutic Effect against Leukemia by a Combination of the Histone Methyltransferase Inhibitor Chaetocin and the Histone Deacetylase Inhibitor Trichostatin A
| Autor: | Il-Kwon Lee, Hoon Kook, Hyeoung-Joon Kim, Je-Jung Lee, Huong Thi Thanh Tran, Jae-Sook Ahn, Yeo-Kyeoung Kim, Kyeong-Soo Park, Hee Nam Kim, Thanh-Nhan Nguyen-Pham |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Adolescent medicine.drug_class Tumor Suppressor Genes Apoptosis HL-60 Cells Hydroxamic Acids Piperazines Histones Young Adult Histone Deacetylase Cell Line Tumor medicine Humans Oncology & Hematology Enzyme Inhibitors Promoter Regions Genetic Histone Methyltransferase Aged Cyclin-Dependent Kinase Inhibitor p15 Histone deacetylase 5 Leukemia biology HDAC11 Chemistry Histone deacetylase inhibitor Acetylation General Medicine Histone-Lysine N-Methyltransferase DNA Methylation Middle Aged Cadherins Molecular biology Frizzled Receptors Histone Deacetylase Inhibitors Leukemia Myeloid Acute Trichostatin A Histone Gene Expression Regulation Histone methyltransferase Cancer research biology.protein Histone Methyltransferases Original Article Histone deacetylase K562 Cells medicine.drug |
| Zdroj: | Journal of Korean Medical Science |
| ISSN: | 1598-6357 1011-8934 |
| Popis: | SUV39H1 is a histone 3 lysine 9 (H3K9)-specific methyltransferase that is important for heterochromatin formation and the regulation of gene expression. Chaetocin specifically inhibits SUV39H1, resulted in H3K9 methylation reduction as well as reactivation of silenced genes in cancer cells. Histone deacetylase (HDAC) inhibitors inhibit deacetylases and accumulate high levels of acetylation lead to cell cycle arrest and apoptosis. In this study, we demonstrated that treatment with chaetocin enhanced apoptosis in human leukemia HL60, KG1, Kasumi, K562, and THP1 cells. In addition, chaetocin induced the expression of cyclin-dependent kinase inhibitor 2B (p15), E-cadherin (CDH1) and frizzled family receptor 9 (FZD9) through depletion of SUV39H1 and reduced H3K9 methylation in their promoters. Co-treatment with chaetocin and HDAC inhibitor trichostatin A (TSA) dramatically increased apoptosis and produced greater activation of genes. Furthermore, this combined treatment significantly increased loss of SUV39H1 and reduced histone H3K9 trimethylation responses accompanied by increased acetylation. Importantly, co-treatment with chaetocin and TSA produced potent antileukemic effects in leukemia cells derived from patients. These in vitro findings suggest that combination therapy with SUV39H1 and HDAC inhibitors may be of potential value in the treatment of leukemia. |
| Databáze: | OpenAIRE |
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