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 describes the effects of GGO on the activity of cysteine-dependent aspartate-directed proteases (caspases) in human leukemia U937 cells. The caspase-3 (CPP32) activity was increased in a time-dependent manner by treatment with 50 microM GGO, whereas no activation of caspase-1 (interleukin-1beta converting enzyme (ICE)) was observed in any time period under the same experimental conditions. Other isoprenyl compounds such as geraniol, geranylgerany-lacetone, and vitamin K2 had no measurable effects on the activities of either caspase-3 or caspase-1. A inhibitor that preferentially inhibits the caspase-3 related caspases, Z-DEVD-FMK, strongly blocked the GGO-induced DNA fragmentation. These results suggest the involvement of caspase-3 in GGO-induced apoptosis in U937 human leukemia cells.
Masuda
Y
Y
School of Pharmaceutical Sciences, Showa University, Shinagawa-ku, Tokyo, Japan.
Nakaya
M
M
Nakajo
S
S
Nakaya
K
K
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D004224:Diterpenes / Q000494:pharmacology*; D004790:Enzyme Induction; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004224:Diterpenes; C017338:geranylgeraniol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D013755:Tetradecanoylphorbol Acetate