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.
Ohizumi
H
H
Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Masuda
Y
Y
Yoda
M
M
Hashimoto
S
S
Aiuchi
T
T
Nakajo
S
S
Sakai
I
I
Ohsawa
S
S
Nakaya
K
K
D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology*; D016259:Genes, myc; D006801:Humans; D014407:Tumor Cells, Cultured
D004224:Diterpenes; C017338:geranylgeraniol