Figure 4
Figure 4. Comparison of cytotoxic activity of apoossypol and gossypol against human B-cell malignancies. NHL B-cell lines bearing t(14;18) translocations (DoHH2, RS11846, and 380) (top) and primary CLL specimens (bottom) were cultured at 106 cells/mL for 48 hours in the absence (vehicle control [white squares]) or presence of various concentrations (log-scale) of gossypol (black circles) or apogossypol (white circles). Percentage viability was determined by staining with FITC–annexin V and PI, scoring viable cells as annexin V negative/PI negative. Data for NHL are representative of several experiments. For CLLs, primary data are shown for 3 patient specimens that had low spontaneous rates of cell death in culture (Rai stage II [n = 1]; Rai stage I [n = 2]), derived from previously untreated patients. Differences in percentage viability between CLLs treated with apogossypol versus gossypol were statistically significant (P < .025 by 2-way ANOVA analysis). An additional 3 CLL specimens were also tested and showed similar sensitivity to gossypol and apogossypol, but higher levels of background cell death precluded determination of LD50 (not shown).

Comparison of cytotoxic activity of apoossypol and gossypol against human B-cell malignancies. NHL B-cell lines bearing t(14;18) translocations (DoHH2, RS11846, and 380) (top) and primary CLL specimens (bottom) were cultured at 106 cells/mL for 48 hours in the absence (vehicle control [white squares]) or presence of various concentrations (log-scale) of gossypol (black circles) or apogossypol (white circles). Percentage viability was determined by staining with FITC–annexin V and PI, scoring viable cells as annexin V negative/PI negative. Data for NHL are representative of several experiments. For CLLs, primary data are shown for 3 patient specimens that had low spontaneous rates of cell death in culture (Rai stage II [n = 1]; Rai stage I [n = 2]), derived from previously untreated patients. Differences in percentage viability between CLLs treated with apogossypol versus gossypol were statistically significant (P < .025 by 2-way ANOVA analysis). An additional 3 CLL specimens were also tested and showed similar sensitivity to gossypol and apogossypol, but higher levels of background cell death precluded determination of LD50 (not shown).

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