Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo
Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo
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DOI：
10.1093/jn/127.5.668
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发表时间：
1997-05-01
影响因子：
4.2
通讯作者：
Elson, CE
中科院分区：
文献类型：
--
作者：
He, L;Mo, HB;Elson, CE
水果、蔬菜和谷物中的各种甲羟戊酸衍生成分（类异戊二烯）抑制肿瘤的生长。本研究估计了在48小时孵育期间抑制鼠B16（F10）黑色素瘤细胞群体增加50%所需的结构多样性类异戊二烯浓度（IC 50值）。I期试验中的单萜类化合物d-柠檬烯和紫苏醇的IC 50值分别为450和250 μ mol/L;相关的环状单萜（紫苏醛、香芹酚和百里酚）、一种无环单萜（香叶醇）和β-胡萝卜素的端环类似物（β-紫罗兰酮）的IC 50值在120-150 μ mol/L范围内。法尼醇（生育三烯酚的侧链类似物）（50 μ mol/L）的IC 50值估计值介于α-生育三烯酚（110 μ mol/L）与γ-（20 μ mol/L）和δ-（10 μ mol/L）生育三烯酚的IC 50值估计值之间。一种在母育酚环上缺少甲基的新型生育三烯酚被证明是非常有效的（IC 50，0.9 μ mol/L）。在两项饮食研究的第一项中，在植入积极生长和高转移性B16（F10）黑色素瘤之前10天和之后28天，向断奶C57 BL雌性小鼠饲喂实验饮食。AIN-76 A饮食中d-γ-生育三烯酚等摩尔（116 μ mol/kg饮食）和维生素E当量（928 μ mol/kg饮食）替代dl-α-生育酚分别使肿瘤生长延迟36%和50%（P < 0.05）。在第二项研究中，在给小鼠喂食用2 mmol/kg d-γ-生育三烯酚、β-紫罗兰酮单独和组合配制的实验饮食之前建立黑素瘤。各处理均显著延长了宿主的存活时间（P < 0.03）。我们的发现，个别类异戊二烯的影响是加性的，这表明植物性饮食的抗癌作用的一个组成部分是水果，蔬菜和谷物的各种类异戊二烯成分的肿瘤生长抑制作用的可能性。
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 mu mol/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 mu mol/L. The IC50 value estimated for farnesol, the side-chain analog of the tocotrienols (50 mu mol/L) fell midway between that of alpha-tocotrienol (110 mu mol/L) and those estimated for gamma- (20 mu mol/L) and delta- (10 mu mol/L) tocotrienol. A novel tocotrienol lacking methyl groups on the tocol ring proved to be extremely 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 prior 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 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.