Neal B. Blatt, Jeffrey J. Bednarski, Roscoe E. Warner, Francesco Leonetti, Kathryn M. Johnson, Anthony Boitano, Raymond Yung, Bruce C. Richardson, Kent J. Johnson, Jonathan A. Ellman, Anthony W. Opipari Jr., Gary D. Glick
Regulation of ROS blocks Bz-423–induced killing. (a) After preincubation of Ramos cells for 30 minutes with FK506 (1 μM, blue), vitamin E (100 μM, red), MnTBAP (100 μM, green), or no inhibitor (black), Bz-423 (10 μM) was added to the cultures. White bars indicate control samples treated with vehicle alone. Using flow cytometry, DHE fluorescence (O2–) was measured at 1 hour, caspase activation at 5 hours, ΔΨm (DiOC6) at 5 hours, and PI permeability and hypodiploid DNA at 24 hours. (b) Effect on cell viability of addition of FK506 at times relative to the addition of Bz-423. The results in a and b represent more than five separate determinations. P < 0.05 for the differences between Bz-423 and control for each inhibitor at each endpoint (Student’s t test).