TY - JOUR
T1 - 5-Aza-2′-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer)
AU - Dai, Zunyan
AU - Liu, Shujun
AU - Marcucci, Guido
AU - Sadee, Wolfgang
PY - 2006/12/15
Y1 - 2006/12/15
N2 - 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.
AB - 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.
KW - 5-Aza-2′-deoxycytidine
KW - Anticancer
KW - BIK (Bcl2-interacting killer)
KW - Depsipeptide
KW - Epigenetics
KW - Synergistic induction
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U2 - 10.1016/j.bbrc.2006.10.055
DO - 10.1016/j.bbrc.2006.10.055
M3 - Article
C2 - 17064661
AN - SCOPUS:33750514048
SN - 0006-291X
VL - 351
SP - 455
EP - 461
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -