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. 2021 Jan 20;5(2):438–450. doi: 10.1182/bloodadvances.2020001461

Figure 3.

Figure 3.

PTC299 enhances effects of decitabine. (A) Apoptosis induced by PTC299 and/or decitabine (DAC). MDS-L and SKM-1 cells were treated with PTC299 and/or DAC for 72 hours, stained with Annexin V and PI, and then analyzed by flow cytometry. Data are shown as mean ± SD (n = 3). *P < .05, **P < .01, ***P < .001 by 1-way ANOVA. (B) Cell-cycle status of MDS-L and SKM-1 cells treated with PTC299 and/or DAC for 72 hours. BrdU was added to the culture 2 hours before the analysis. (C) Cell-cycle status of MDS-L cells treated with PTC299 only for 48 hours followed by combination therapy with DAC. BrdU was added to the culture 2 hours before the analysis. (D) Schematic representation of the pyrimidine synthesis pathway and the target step in which DAC is incorporated into DNA. A proposed model of DAC incorporation into DNA in normal and cytidine starved states is depicted (bottom). (E) DAC incorporation into DNA in MDS-L cells in the presence of PTC299 for 24 hours. MDS-L cells were cultured in the presence of 0, 100, and 200 nM DAC for 24 hours with and without 30 nM PTC299. The amounts of DAC incorporated into DNA were assessed by an LC-MS/MS analysis.