Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism
Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism
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DOI：
10.1093/jn/131.11.3027s
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发表时间：
2001-11-01
影响因子：
4.2
通讯作者：
Fahey, JW
中科院分区：
文献类型：
--
作者：
Talalay, P;Fahey, JW
几项流行病学研究表明，食用十字花科蔬菜可能特别有效（与水果和蔬菜的总消费量相比），可以降低几个器官部位的癌症风险。广泛食用的十字花科植物特别富含芥子油苷，芥子油苷被植物黑芥子酶和胃肠道微生物菌群转化为异硫氰酸酯。在动物模型中，一些异硫氰酸酯和有限数量的芥子油苷被有效地阻断了化学致癌作用。许多异硫氰酸酯也是2相蛋白的有效诱导剂。大量证据支持这样的观点，即2相酶诱导是降低致癌物敏感性的一种非常有效的策略。这一结论最近得到了强有力的分子支持，在小鼠实验中，特异性转录因子nrf2，这是必不可少的诱导2相蛋白，被删除。在这些基因敲除小鼠中，2相酶的基础水平非常低，并且不可诱导。因此，这些小鼠比野生型小鼠更容易受到苯并[a]芘前胃致癌作用的影响，并且不受2期诱导剂的保护。这些实验为第二阶段酶在控制接触致癌物的风险方面的主要作用提供了非常有力的证据。正在鉴定越来越多的发挥各种保护机制的2期蛋白。因此，除了解毒亲电体，这些蛋白质行使多功能，持久和催化抗氧化保护。
Several epidemiologic studies suggest that consumption of cruciferous vegetables may be particularly effective (compared with total fruit and vegetable consumption) in reducing cancer risk at several organ sites. Crucifers that are widely consumed are especially rich in glucosinolates, which are converted by plant myrosinase and gastrointestinal microflora to isothiocyanates. A number of isothiocyanates and a limited number of glucosinolates that were examined effectively block chemical carcinogenesis in animal models. Many isothiocyanates are also potent inducers of phase 2 proteins. Substantial evidence supports the view that phase 2 enzyme induction is a highly effective strategy for reducing susceptibility to carcinogens. This conclusion has recently received strong molecular support from experiments on mice in which the specific transcription factor, nrf2, which is essential for induction of phase 2 proteins, was deleted. In these knock-out mice, the basal levels of phase 2 enzymes are very low and not inducible. Accordingly, these mice are much more susceptible than their wild-type counterparts to benzo[a]pyrene forestomach carcinogenesis and are not protected by phase 2 inducers. These experiments provide very strong evidence for a major role of phase 2 enzymes in controlling the risk of exposure to carcinogens. An increasing number of phase 2 proteins that exert a variety of protective mechanisms are being identified. Thus, in addition to detoxifying electrophiles, these proteins exercise versatile, long-lasting and catalytic antioxidant protection.