Effects of isoprenoid compounds on human solid cancer cells

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We examined the effects of isoprenoid compounds such as geranylgeraniol and vitamin 1(2 or various solid cancer cell lines derived from human tissues. Geranylgeraniol induced apoptosis in every cancer cells examined in the present study. The 1C50 values range from 3O-9O muM.On the other hand, vitamin K2 that also contains a geranylgeranyl group in the molecule induced apoptosis only in two cell lines such as pancreatic cancer MIA-PaCa 2 cells and ovary cancer TYK-nu cells. When these cells were treated with vitamin K2, they shrank and small apoptotic bodies were formed 4 days after the incubation. Cycloheximide and actinomycin D inhibited the induction of apoptosis by vitamin K2, suggesting protein synthesis is necessary for apoptosis by vitamin K2. By contrast, the apoptosis induced by geranylgeraniol was not inbhibited by cycloheximide. In leukemia U937 cells, both JNK and caspase 3 were activated by the treatment with geranylgeraniol, while these enzymes were not activated by vitamin K2. These results suggest that geranylgeraniol and vitamin K2 might induce apoptosis by different mechanisms.