A sequential treatment of depsipeptide followed by 5-azacytidine enhances Gadd45β expression in hepatocellular carcinoma cells

Chunling Jiang, Bingsen Zhou, Kenneth Fan, Eric Heung, Lijun Xue, Xiyong Liu, Mark Kirschbaum, Yun Yen

研究成果: 雜誌貢獻文章

12 引文 (Scopus)

摘要

Background: DNA methylation can influence histone modification and gene expression. The growth-arrest DNA damage inducible gene 45β (Gadd45β) has been reported as a potential diagnostic marker for aggressive hepatocellular carcinoma. In this study, the synergistic effect of the histone deacetylase inhibitor depsipeptide and the DNA methyltransferase inhibitor 5-azacytidine on the Gadd45β gene expression in human liver cells was examined. Materials and Methods: The effects of depsipeptide and 5-azacytidine in CL-48, HepG2 and Hep3B cells were examined by PCR, cell viability test, Western blot and chromatin immunoprecipitation assay. Results: Two μM depsipeptide reactivated Gadd45β gene expression considerably within 4 h in HepG2 cells, but not in CL-48 or Hep3B cells. Up to 10 μM 5-azacytidine had no reactivation effect on Gadd45β. A sequential treatment of depsipeptide+5-azacytidine (but not 5-azacytidine+depsipeptide) exhibited a synergistic effect on Gadd45β gene reactivation in the HepG2 cells. Conclusion: The results show for the first time that histone acetylation in sequence with hypermethylation can override transcriptional repression. Our results provide a novel insight into the epigenetics-based strategy for treating human liver cancer.

原文英語
頁(從 - 到)3783-3789
頁數7
期刊Anticancer Research
27
發行號6 B
出版狀態已發佈 - 十一月 1 2007
對外發佈Yes

指紋

Depsipeptides
Azacitidine
DNA Damage
Hepatocellular Carcinoma
Gene Expression
Hep G2 Cells
Growth
Genes
Histone Code
Histone Deacetylase Inhibitors
Chromatin Immunoprecipitation
Methyltransferases
DNA Methylation
Acetylation
Liver Neoplasms
Epigenomics
Histones
Cell Survival
Western Blotting
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

A sequential treatment of depsipeptide followed by 5-azacytidine enhances Gadd45β expression in hepatocellular carcinoma cells. / Jiang, Chunling; Zhou, Bingsen; Fan, Kenneth; Heung, Eric; Xue, Lijun; Liu, Xiyong; Kirschbaum, Mark; Yen, Yun.

於: Anticancer Research, 卷 27, 編號 6 B, 01.11.2007, p. 3783-3789.

研究成果: 雜誌貢獻文章

Jiang, C, Zhou, B, Fan, K, Heung, E, Xue, L, Liu, X, Kirschbaum, M & Yen, Y 2007, 'A sequential treatment of depsipeptide followed by 5-azacytidine enhances Gadd45β expression in hepatocellular carcinoma cells', Anticancer Research, 卷 27, 編號 6 B, 頁 3783-3789.
Jiang, Chunling ; Zhou, Bingsen ; Fan, Kenneth ; Heung, Eric ; Xue, Lijun ; Liu, Xiyong ; Kirschbaum, Mark ; Yen, Yun. / A sequential treatment of depsipeptide followed by 5-azacytidine enhances Gadd45β expression in hepatocellular carcinoma cells. 於: Anticancer Research. 2007 ; 卷 27, 編號 6 B. 頁 3783-3789.
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abstract = "Background: DNA methylation can influence histone modification and gene expression. The growth-arrest DNA damage inducible gene 45β (Gadd45β) has been reported as a potential diagnostic marker for aggressive hepatocellular carcinoma. In this study, the synergistic effect of the histone deacetylase inhibitor depsipeptide and the DNA methyltransferase inhibitor 5-azacytidine on the Gadd45β gene expression in human liver cells was examined. Materials and Methods: The effects of depsipeptide and 5-azacytidine in CL-48, HepG2 and Hep3B cells were examined by PCR, cell viability test, Western blot and chromatin immunoprecipitation assay. Results: Two μM depsipeptide reactivated Gadd45β gene expression considerably within 4 h in HepG2 cells, but not in CL-48 or Hep3B cells. Up to 10 μM 5-azacytidine had no reactivation effect on Gadd45β. A sequential treatment of depsipeptide+5-azacytidine (but not 5-azacytidine+depsipeptide) exhibited a synergistic effect on Gadd45β gene reactivation in the HepG2 cells. Conclusion: The results show for the first time that histone acetylation in sequence with hypermethylation can override transcriptional repression. Our results provide a novel insight into the epigenetics-based strategy for treating human liver cancer.",
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AU - Kirschbaum, Mark

AU - Yen, Yun

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