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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3783-3789
Number of pages7
JournalAnticancer Research
Volume27
Issue number6 B
Publication statusPublished - Nov 1 2007
Externally publishedYes

Keywords

  • 5-azacytidine
  • Depsipeptide
  • Gadd45β
  • HCC
  • Synergistic effect

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    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, 27(6 B), 3783-3789.