Elson C E, Yu S G
Department of Nutritional Sciences, University of Wisconsin, Madison 53706-1571.
J Nutr. 1994 May;124(5):607-14. doi: 10.1093/jn/124.5.607.
Anutritive isoprenoid constituents of fruits, vegetables, cereal grains and essential oils exhibit a spectrum of anticarcinogenic activities. The induction of hepatic Phase II detoxifying activities by dietary isoprenoids appears to underlie their blocking action. The second anticarcinogenic action of the dietary isoprenoids, suppression of the growth of chemically initiated and transplanted tumors is, we suggest, secondary to the inhibition of mevalonate pathway activities. Mevinolin, a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activity, depletes cells of the intermediate products of the pathway that are required for the posttranslational modification of proteins, a process giving the proteins lipophilic anchors that bind to membranes. As a consequence, nuclear lamins and ras oncoproteins remain in nascent states, and cells do not proliferate. gamma-Tocotrienol, perillyl alcohol, geraniol and d-limonene suppress hepatic HMG-CoA reductase activity, a rate-limiting step in cholesterol synthesis, and modestly lower serum-cholesterol levels of animals. These isoprenoids also suppress tumor growth. The HMG-CoA reductase of neoplastic tissues differs from that of sterologenic tissues in being markedly resistant to sterol feedback inhibition. Our review suggests that the mevalonate pathway of tumor tissues is uniquely sensitive to the inhibitory actions of the dietary isoprenoids.
水果、蔬菜、谷物和香精油中的无营养类异戊二烯成分具有一系列抗癌活性。膳食类异戊二烯诱导肝脏II相解毒活性似乎是其阻断作用的基础。我们认为，膳食类异戊二烯的第二种抗癌作用，即抑制化学引发和移植肿瘤的生长，是甲羟戊酸途径活性受到抑制的继发结果。美伐他汀是3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶活性的竞争性抑制剂，它会耗尽细胞中蛋白质翻译后修饰所需的该途径中间产物，而这一过程会赋予蛋白质与膜结合的亲脂性锚定物。结果，核纤层蛋白和ras癌蛋白保持新生状态，细胞无法增殖。γ-生育三烯酚、紫苏醇、香叶醇和d-柠檬烯会抑制肝脏HMG-CoA还原酶活性，这是胆固醇合成中的限速步骤，并适度降低动物的血清胆固醇水平。这些类异戊二烯也会抑制肿瘤生长。肿瘤组织中的HMG-CoA还原酶与甾体生成组织中的不同，它对甾醇反馈抑制具有明显抗性。我们的综述表明，肿瘤组织的甲羟戊酸途径对膳食类异戊二烯的抑制作用具有独特的敏感性。
