GERANYLGERANIOL POTENTLY INDUCES CASPASE-3-LIKE ACTIVITY DURING APOPTOSIS IN HUMAN LEUKEMIA U937 CELLS

In a previous study, we showed that geranylgeraniol (GGO) is a potent inducer of apoptosis in human leukemia cells. The present study descri bes the effects of GGO on the activity of cysteine-dependent aspartate -directed proteases (caspases) in human leukemia U937 cells. The caspa se-3 (CPP32) activity was increased in a time-dependent manner by trea tment with 50 mu M GGO, whereas no activation of caspase-1 (interleuki n-1 beta converting enzyme (ICE)) was observed in any time period unde r the same experimental conditions. Other isoprenyl compounds such as geraniol, geranylgeranylacetone, and vitamin K-2 had no measurable eff ects on the activities of either caspase-3 or caspase-1. A inhibitor t hat preferentially inhibits the caspase-3 related caspases, Z-DEVD-FMK , strongly blocked the GGO-induced DNA fragmentation. These results su ggest the involvement of caspase-3 in GGO induced apoptosis in U937 hu man leukemia cells. (C) 1997 Academic Press.