Figure 3
From: Cell cycle-dependent activity of the novel dual PI3K-MTORC1/2 inhibitor NVP-BGT226 in acute leukemia
Evaluation of dual PI3K/MTOR inhibition in mutant-TK AKT-activated acute leukemia cell lines. (A) MOLM14 cells harboring a FLT3 ITD and K562 cells harboring a BCR-ABL1 gain-of-function mutation are treated with NVP-BGT226 or NVP-BEZ235 and cellular proliferation is measured using an XTT-based assay. Both inhibitors reveal high antiproliferative potency in both cell lines. IC50s are provided at the bottom of each graph. (B) Dual PI3K/MTOR inhibition using NVP-BGT226 or NVP-BEZ235 reveals agent-specific induction of apoptosis in MOLM14 and K562 cells – with NVP-BGT226 the by far more potent agent. Linear regression analysis to calculate IC50s is provided at the bottom of each graph. (C) Cell cycle analyses of MOLM14 cells treated with either agent demonstrate strong G1/G0 arrest with failure to induce meaningful apoptosis for NVP-BEZ235 exposed cells. In contrast, NVP-BGT226 treated cells (bottom panels) show a time-dependent increase of the sub-G1/G0 fraction, indicating apoptotic/dead cells. (D) Similar effects on cell cycle regulation are shown for the K562 cell line treated with either NVP-BEZ235 or NVP-BGT226 – with a strong G1/G0 arrest for NVP-BEZ235 but potent and time-dependent increase of the apoptotic/dead cell fraction for NVP-BGT226.