Sundry mevalonate-derived constituents (isoprenoids) of fruits, vegeta
bles and cereal grains suppress the growth of tumors. This study estim
ated the concentrations of structurally diverse isoprenoids required t
o inhibit the increase in a population of murine B16(F10) melanoma cel
ls during a 48-h incubation by 50% (IC50 value). The IC50 values for d
-limonene and perillyl alcohol, the monoterpenes in Phase I trials, we
re 450 and 250 mu mol/L, respectively; related cyclic monoterpenes (pe
rillaldehyde, carvacrol and thymol), an acyclic monoterpene (geraniol)
and the end ring analog of beta-carotene (beta-ionone) had IC50 value
s in the range of 120-150 mu mol/L. The IC50 value estimated for farne
sol, the side-chain analog of the tocotrienols (50 mu mol/L) fell midw
ay between that of alpha-tocotrienol (110 mu mol/L) and those estimate
d for gamma- (20 mu mol/L) and delta- (10 mu mol/L) tocotrienol. A nov
el tocotrienol lacking methyl groups on the tocol ring proved to be ex
tremely potent (IC50, 0.9 mu mol/L). In the first of two diet studies,
experimental diets were fed to weanling C57BL female mice for 10 d pr
ior to and 28 d following the implantation of the aggressively growing
and highly metastatic B16(F10) melanoma. The isomolar (116 mu mol/kg
diet) and the Vitamin E-equivalent (928 mu mol/kg diet) substitution o
f d-gamma-tocotrienol for dl-alpha-tocopherol in the AIN-76A diet prod
uced 36 and 50% retardations, respectively, in tumor growth (P < 0.05)
. In the second study, melanomas were established before mice were fed
experimental diets formulated with 2 mmol/kg d-gamma-tocotrienol, bet
a-ionone individually and in combination. Each treatment increased (P
< 0.03) the duration of host survival. Our finding that the effects of
individual isoprenoids were additive suggests the possibility that on
e component of the anticarcinogenic action of plant-based diets is the
tumor growth-suppressive action of the diverse isoprenoid constituent
s of fruits, vegetables and cereal grains.