Effects of TK inhibitors on apoptosis of HMC-1 cells. (A-F) HMC-1.1 cells (A,C,E) and HMC-1.2 cells (B,D,F) were cultured in the absence (Co) or presence of various concentrations of PKC412 (A-B), AMN107 (C-D), or imatinib (E-F), as indicated, for 24 hours. Thereafter, the percentages of apoptotic cells were quantified by light microscopy. Results represent the mean ± SD of 3 independent experiments. ^*P < .05 compared with control. (G) Electron microscopic examination of PKC412-induced apoptosis in HMC-1 cells. HMC-1.2 cells were incubated with control medium or PKC412 (500 nM or 900 nM as indicated) at 37°C for 24 hours. Then, cells were harvested and analyzed for ultrastructural signs of apoptosis. Whereas apoptotic cells were rarely seen in cultures kept with control medium, HMC-1.2 cells cultured in PKC412 frequently displayed signs of apoptosis including cell shrinkage, membrane ruffling, vacuolization, and condensation of the nuclear chromatin. Original magnification, 5000 ×. Images were captured using a Gatan Bioscan Camera model 792 and Digital Micrograph acquisition software (Gatan, Pleasanton, CA). (H) HMC-1.2 cells were exposed to control medium (Control), PKC412 (1 μM), AMN107 (1 μM), or imatinib (1 μM) at 37°C for 24 hours. Then, cells were examined for viability and apoptosis by combined propidium iodide (PI)/annexin V-FITC staining.