Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells

  • Authors: Eun Ju Lee, Bo Bin Lee, Soon-Ja Kim, Yong-Doo Park, Joobae Park, Duk-Hwan Kim
  • View Affiliations

  • Published online on: Wednesday, October 1, 2008
  • Pages: 767-776
  • DOI: 10.3892/ijo_00000063

Abstract

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 µM concentrations and G1 and G2/M arrest at 2.0 µM. 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.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Lee, E., Lee, B., Kim, S., Park, Y., Park, J., & Kim, D. (2008). Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. International Journal of Oncology, 33(4), 767-776.
MLA
Lee, Lee, Kim, Park, Park, and Duk-Hwan Kim. "Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells." International Journal of Oncology International Journal of Oncology 33.4 (2008): 767-776.
Chicago
Lee, Lee, Kim, Park, Park, and Duk-Hwan Kim. "Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 767-776.