Figure 3.

Caspase-independent forms of membrane lysis unaffected by P-gp overexpression. CEM cell lines, CCRF (P-gp^low) or A7⁺ (P-gp^high) were labeled with ⁵¹Cr (lysis; a, c, and e) and ¹²⁵IUdR (DNA fragmentation; b, d, and f) for 1 h, washed in growth media, and incubated for 4 h in 96-well plates (2 × 10⁴ cells/well) with cell death stimuli at final concentrations as follows: (a and b) pfp (300 units); (c and d) pfp (30 units) and gB (0.5 μg/ml); and (e and f) NK cells at effector/target ratios as shown. In some wells CCRF or A7⁺ cells were preincubated for 30 min with anti-P-gp mAb (MRK-16) (50 μg/ml, final concentration) and/or followed by 20 μM (final concentration) ZVAD-fmk or control ZFA-fmk inhibitor for 30 min. Cell death stimuli then were added as indicated for 4 h (NT = not tested). gB alone at these concentrations was without effect. These data are calculated as the mean ± SE of duplicate samples and are representative of at least two different experiments.