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 language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Dec 15 2006|
- BIK (Bcl2-interacting killer)
- Synergistic induction