Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo.

Abstract

Sundry mevalonate-derived constituents (isoprenoids) of fruits, vegetables and cereal grains suppress the growth of tumors. This study estimated the concentrations of structurally diverse isoprenoids required to inhibit the increase in a population of murine B16(F10) melanoma cells during a 48-h incubation by 50% (IC50 value). The IC50 values for d-limonene and perillyl alcohol, the monoterpenes in Phase I trials, were 450 and 250 micromol/L, respectively; related cyclic monoterpenes (perillaldehyde, carvacrol and thymol), an acyclic monoterpene (geraniol) and the end ring analog of beta-carotene (beta-ionone) had IC50 values in the range of 120-150 micromol/L. The IC50 value estimated for farnesol, the side-chain analog of the tocotrienols (50 micromol/L) fell midway between that of alpha-tocotrienol (110 micromol/L) and those estimated for gamma- (20 micromol/L) and delta- (10 micromol/L) tocotrienol. A novel tocotrienol lacking methyl groups on the tocol ring proved to be extremely potent (IC50, 0.9 micromol/L). In the first of two diet studies, experimental diets were fed to weanling C57BL female mice for 10 d prior to and 28 d following the implantation of the aggressively growing and highly metastatic B16(F10) melanoma. The isomolar (116 micromol/kg diet) and the Vitamin E-equivalent (928 micromol/kg diet) substitution of d-gamma-tocotrienol for dl-alpha-tocopherol in the AIN-76A diet produced 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, beta-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 one component of the anticarcinogenic action of plant-based diets is the tumor growth-suppressive action of the diverse isoprenoid constituents of fruits, vegetables and cereal grains.

• Authors: L He, H Mo, S Hadisusilo, A A Qureshi, C E Elson
• Journal: The Journal of nutrition (J Nutr) Vol. 127 Issue 5 Pg. 668-74 (May 1997) ISSN: 0022-3166 [Print] United States
• PMID: 9164984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chromans
• Norisoprenoids
• Terpenes
• Vitamin E
• plastochromanol 8
• beta-ionone
• Mevalonic Acid

Topics

• Animals
• Cell Division (drug effects, physiology)
• Cell Transformation, Neoplastic (drug effects, pathology)
• Chromans (analysis, pharmacology)
• Dose-Response Relationship, Drug
• Edible Grain (chemistry)
• Female
• Fruit (chemistry)
• Melanoma, Experimental (pathology, physiopathology)
• Mevalonic Acid (metabolism)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Norisoprenoids
• Terpenes (analysis, pharmacology)
• Time Factors
• Tumor Cells, Cultured
• Vegetables (chemistry)
• Vitamin E (analogs & derivatives, analysis, pharmacology)