Document Detail


Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells.
MedLine Citation:
PMID:  18813790     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Histone deacetylase inhibitors (HDACIs) are involved in cell growth, apoptosis and differentiation. This study aimed to investigate the effects of HDACI scriptaid on histone modification, demethylation, cell growth, cell cycle and apoptosis in the RKO colorectal cancer cell line and screening for scriptaid-induced genes. RKO cells were treated with 5-aza-2'-deoxycytidine (5-aza-dC), trichostatin A (TSA) or scriptaid at different concentrations. Histone modification and methylation status of a silenced p16 gene were analyzed using chromatin immunoprecipitation and methylation-specific PCR, respectively. Flow cytometry was performed for the analysis of cell cycle and apoptosis. Scriptaid-induced expression was analyzed using Human OneArray chip. Scriptaid resulted in the demethylation and re-expression of a hypermethylated p16 gene along with 5-aza-dC synergistically in the RKO cells, but not alone. Scriptaid induced modifications of core histone tails important in euchromatin structure: increases in acetyl-H3-K9 and dimethyl-H3-K4 and a decrease in dimethyl-H3-K9. Cell growth was inhibited by scriptaid in a dose-dependent manner. Cell cycle analysis showed that scriptaid induced G1 arrest at 0.5 and 1.0 microM concentrations and G1 and G2/M arrest at 2.0 microM. Scriptaid did not have a significant effect on apoptosis in RKO cells. An altered expression of 278 genes was observed in RKO cells in response to scriptaid treatment. In conclusion, the present study suggests that scriptaid may be effective in growth suppression and cell cycle arrest and in the reversal of repressive chromatin marks at the promoter region of a hypermethylated p16 gene in colorectal cancer.
Authors:
Eun Ju Lee; Bo Bin Lee; Soon-Ja Kim; Yong-Doo Park; Joobae Park; Duk-Hwan Kim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  33     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-24     Completed Date:  2008-11-13     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  767-76     Citation Subset:  IM    
Affiliation:
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Azacitidine / analogs & derivatives,  pharmacology
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Colonic Neoplasms / drug therapy*,  genetics*
DNA Methylation
Enzyme Inhibitors / pharmacology
Epigenesis, Genetic*
Gene Expression Regulation, Neoplastic*
Genes, p16
Histone Deacetylase Inhibitors*
Humans
Hydroxylamines / pharmacology*
Promoter Regions, Genetic
Quinolines / pharmacology*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Hydroxylamines; 0/Quinolines; 0/scriptaid; 320-67-2/Azacitidine; 776B62CQ27/decitabine

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