DNA methyltransferase inhibitors (DNMTIs), including decitabine (DAC) and 
azacitidine (AZA), have recently been highlighted for the treatment of high-risk 
myelodysplastic syndrome (MDS); however, their action mechanisms have not been 
clearly defined. Therefore, we investigated the effects of DNMTIs on MDS-derived 
cell lines in vitro. An MDS-derived cell line MDS92 and its blastic subline 
MDS-L and HL-60 were used. All three cell lines were sensitive to DNMTIs, but 
MDS-L was the most susceptible. DAC-induced cell death in MDS-L was preceded by 
DNA damage-induced G2 arrest via a p53-independent pathway. AZA did not 
influence the pattern of cell cycle, although it induced DNA damage response. 
The IC(50) of DAC or AZA on MDS-L cells was associated with the dose inducing 
the maximal hypomethylation in long interspersed nuclear elements-1 (LINE-1) 
methylation assay. AZA suppressed the level of methylation in a time-dependent 
manner (days 4, 7, and 10), whereas DAC maintained the level of methylation from 
day 4 to 11. The protein expression of DNMT1 and DNMT3a decreased with the 
suppression of growth and methylation. We conclude that this study provides 
in vitro models for understanding the effects of DNMTIs on cell growth and gene 
regulation, including differences in the possible action mechanism of DAC and 
AZA.