Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo.
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.
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Department of Nutritional Sciences, University of Wisconsin, Madison 53706, USA.
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Hadisusilo
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Qureshi
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Elson
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D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D002839:Chromans / Q000032:analysis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D002523:Edible Grain / Q000737:chemistry; D005260:Female; D005638:Fruit / Q000737:chemistry; D008546:Melanoma, Experimental / Q000473:pathology* / Q000503:physiopathology; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D045792:Norisoprenoids; D013729:Terpenes / Q000032:analysis / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014675:Vegetables / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology
D002839:Chromans; D045792:Norisoprenoids; D013729:Terpenes; D014810:Vitamin E; C013649:plastochromanol 8; C008157:beta-ionone; D008798:Mevalonic Acid