Figure 1.

TAE684 inhibits cell proliferation, induces apoptosis and cell cycle arrest, and inactivates EML4-ALK signaling of H2228 cells. (A) TAE684 reduces H2228 cell survival. Cells were treated with indicated concentrations of TAE684 and cell viability was measured by CellTiterGlo 72 hours after treatment. (B, C) TAE684 induces apoptosis. Cells were treated with indicated concentrations of TAE684. Caspase 3/7 activation was measured by Cap3/7Glo 48 hours after treatment (B). Cells were treated with 50 or 200 nM TAE684; apoptosis was measured at indicated time by annexin V stain 72 hours after treatment (C). (D) TAE684 induces G₁ arrest. Cells were treated with 200 nM TAE684 for 24 hours, arrested at G₁/S transition with HU, and released into the S phase. Cells were harvested at indicated time, stained with PI, and analyzed for cell cycle distribution. Percentage of cells in G₁ at various time points is shown. (E) TAE684 inhibits ALK signaling. Cells were treated with 50 nM TAE684 for 6 hours, and Western blot analysis was performed to determine phosphorylation of ALK, Akt, ERK, and STAT3.