1. Prediction of novel cell cycle inhibitors based on CODIM1.
Prediction of novel cell cycle inhibitors based on CODIM1. (A) Heatmap: expression fold change in each cell line with shaded columns, indicating chemical treatments not present in the respective cell‐line‐specific module. Grey: compounds with a known effect on cell cycle (Supplementary Table 5). Although, six well‐known cell cycle blockers were detected in all cell lines delineating a module core in CODIM1, 26 additional cell cycle blockers were only detected as part of this module in one or two of the three cell lines (shaded columns). This variability highlights the benefits of aggregating information across cell lines. (B) Three chemicals not previously known to inhibit cell cycle were examined in cell viability and proliferation assays. For sulconazole and vinburnine dose‐dependent reduction of cell viability and proliferation were confirmed in two cell lines with IC50 values as indicated. For mephentermine, an effect on cell viability and proliferation could not be detected in either cell line (treat., treatment). (C) Control and drug‐treated HL60 cells were attributed to different cell cycle phases according to their DNA content (PI, FACS analysis) for three treatment durations (24, 48 and 96 h). The error bars represent the s.e.m. Sulconazole (25 μM) treatment led to a marked increase in sub‐G1 population across all time points (24, 48 and 96 h), which is indicative of an apoptotic cell population. Vinburnine (25 μM) induced a G2/M arrest within 24 h similar to Nocodazole (Supplementary Figure 9) and further treatment (48 and 96 h) resulted in increased apoptosis in HL60 cells.
Murat Iskar et al. Mol Syst Biol 2013;9:662
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