Farnesylamine, an analogue of farnesol, was shown to inhibit growth of
PAP2 cells (ras-transformed NIH 3T3 cells) in a dose-dependent manner
. This inhibition was overcome by adding farnesol to the culture mediu
m, but not by adding geranylgeraniol, squalene, cholesterol, dolichol,
myristic acid or palmitic acid. Farnesylamine inhibited both farnesyl
/protein transferase and geranylgeranyl/protein transferase in whole c
ell extracts and also inhibited the prenylation of proteins, particula
rly ras p21, in PAP2 cells. Inhibition of prenylation was associated w
ith increased biosynthesis of other products of the mevalonate biosynt
hetic pathway. These observations suggest that inhibition of the growt
h of PAP2 cells by farnesylamine may be due to blocking of ras-mediate
d signal transduction. This offers a means of investigating mechanisms
involved in ras action and raises the possibility of developing novel
strategies for anticancer therapy.