Induction of apoptosis in various tumor cell lines by geranylgeraniol.

We have found that GGO is a potent inducer of apoptosis in various human tumor cell lines, including a myeloid multipotential leukemia K562 cell line which is resistant to the induction of apoptosis by various apoptosis-inducing agents and conditions. Polyprenylalcohols with isoprenyl units shorter than the geranylgeranyl group or longer than farnesyl group were less effective in inducing apoptosis in myeloid leukemia HL-60 cells and polyprenylketones had no apoptosis-inducing activity. The fragmentation of DNA in HL-60 cells by GGO was so rapid, no significant effect on the cell cycle was observed. [3H]GGO was taken up by HL-60 cells in 3 h and was incorporated into several proteins. The expression of c-myc and bcl-2 decreased significantly within 3 h of the start of the treatment of HL-60 cells with 50 microM GGO.