5-Aza-2′-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer)

Zunyan Dai, Shujun Liu, Guido Marcucci, Wolfgang Sadee

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

DNA methylation and histone acetylation are main epigenetic events regulating gene expression, serving as anticancer drug targets. A combination of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine with the histone deacetylase inhibitor depsipeptide synergistically induces apoptosis. To characterize genes involved in this process, we measured expression of 376 apoptosis-related genes with microarrays after treatment with the two inhibitors alone or in combination. The pro-apoptotic BIK (Bcl2-interacting killer) was the only gene synergistically upregulated in all four cancer cell lines tested (A549, PC-3, TK-10, and UO-31). BIK induction was confirmed by RT-PCR and Western blots. Histone acetylation of the BIK promoter region increased with depsipeptide treatment but was not further affected by 5-aza-2′-deoxycytidine. In summary, synergistic upregulation of pro-apoptotic BIK-previously shown to suppress tumor growth-appears to play a critical role in anticancer effects of 5-aza-2′-deoxycytidine plus depsipeptide.

Original languageEnglish (US)
Pages (from-to)455-461
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume351
Issue number2
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

Keywords

  • 5-Aza-2′-deoxycytidine
  • Anticancer
  • BIK (Bcl2-interacting killer)
  • Depsipeptide
  • Epigenetics
  • Synergistic induction

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