ISOPRENOIDS SUPPRESS THE GROWTH OF MURINE B16 MELANOMAS IN-VITRO AND IN-VIVO

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.