Figure 6
Figure 6. Inhibition of PI3K-AKT signaling and up-regulation of apoptosis-related proteins by PIK-90 and PI-103. (A) PIK-90 and PI-103 reduce CXCL12-induced phosphorylation of Akt (especially at Ser473) and of its downstream effector S6 ribosomal protein (at Ser235/236 and Ser240/244) and produce a trend to increased cleavage of the apoptosis-related proteins caspase 7 and its target poly-(ADP-ribose) polymerase (PARP). To generate the bar graphs, (phospho)protein expression of B CLL cells from 5 different patients was quantified with RPPA, and the quantification data were then corrected for loading and normalized to controls that were stimulated with CXCL12 but not preincubated with PI3K inhibitors. Each bar represents the mean (± SEM; n = 5) relative quantity of the (phospho)proteins that are displayed on the right vertical axis after pretreatment with the PI3K inhibitors that are indicated on the left vertical axis and stimulation of all samples with CXCL12 for 5 minutes. *Significant differences from the control samples. (B) Heat map showing decreases in phosphorylation of PI3K-AKT signaling proteins and increases of the apoptosis-related proteins cleaved caspase 7 and cleaved PARP in 5 different CLL patients after treatment with PI3K inhibitors. To generate this heat map, protein expression was quantified with RPPA, and the quantification data were corrected for loading and normalized to respective control samples from each patient who were stimulated with CXCL12 but not pretreated with PI3K inhibitors. Each square represents expression levels of the respective proteins indicated on the vertical axis for one individual CLL sample. The PI3K inhibitors and their respective concentrations are displayed on the top horizontal axis, whereas the bottom horizontal axis indicates that all samples were stimulated for 5 minutes with CXCL12. Shades of red and green indicate up- or down-regulation of a given (phospho)protein, respectively, in comparison with the levels in untreated control cells from each patient (the latter were normalized to a black color in each case).

Inhibition of PI3K-AKT signaling and up-regulation of apoptosis-related proteins by PIK-90 and PI-103. (A) PIK-90 and PI-103 reduce CXCL12-induced phosphorylation of Akt (especially at Ser473) and of its downstream effector S6 ribosomal protein (at Ser235/236 and Ser240/244) and produce a trend to increased cleavage of the apoptosis-related proteins caspase 7 and its target poly-(ADP-ribose) polymerase (PARP). To generate the bar graphs, (phospho)protein expression of B CLL cells from 5 different patients was quantified with RPPA, and the quantification data were then corrected for loading and normalized to controls that were stimulated with CXCL12 but not preincubated with PI3K inhibitors. Each bar represents the mean (± SEM; n = 5) relative quantity of the (phospho)proteins that are displayed on the right vertical axis after pretreatment with the PI3K inhibitors that are indicated on the left vertical axis and stimulation of all samples with CXCL12 for 5 minutes. *Significant differences from the control samples. (B) Heat map showing decreases in phosphorylation of PI3K-AKT signaling proteins and increases of the apoptosis-related proteins cleaved caspase 7 and cleaved PARP in 5 different CLL patients after treatment with PI3K inhibitors. To generate this heat map, protein expression was quantified with RPPA, and the quantification data were corrected for loading and normalized to respective control samples from each patient who were stimulated with CXCL12 but not pretreated with PI3K inhibitors. Each square represents expression levels of the respective proteins indicated on the vertical axis for one individual CLL sample. The PI3K inhibitors and their respective concentrations are displayed on the top horizontal axis, whereas the bottom horizontal axis indicates that all samples were stimulated for 5 minutes with CXCL12. Shades of red and green indicate up- or down-regulation of a given (phospho)protein, respectively, in comparison with the levels in untreated control cells from each patient (the latter were normalized to a black color in each case).

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