Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms.
Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms.
复制标题
DOI：
--
复制
发表时间：
1994-04
期刊：
影响因子：
11.2
通讯作者：
Yuesheng Zhang;P. Talalay
中科院分区：
文献类型：
--
作者：
Yuesheng Zhang;P. Talalay
有机异硫氰酸酯可阻止不同致癌物(多环芳烃、偶氮染料、乙硫氨酸、N-2-荧乙酰胺和亚硝胺)在啮齿动物体内诱导肿瘤的产生。α-萘基、β-萘基、苯乙基和其他芳基烷基异硫氰酸酯对肝脏、肺、乳腺、前胃和食道的肿瘤发展具有保护作用。许多异硫氰酸酯及其硫代葡萄糖苷前体(β-硫代葡萄糖苷，N-羟基硫酸盐)天然存在于人类食用的植物中，有时大量存在于十字花科蔬菜中。然而，异硫氰酸酯和硫代葡萄糖苷对大量食用蔬菜的抗癌保护作用的可能贡献尚不清楚。异硫氰酸酯的抗癌作用似乎是通过串联和协同机制介导的：(A)细胞色素P-450抑制致癌物质的激活，可能是通过下调酶水平并直接抑制其催化活性，从而降低最终致癌物质的水平；以及(B)诱导第二相酶，如谷胱甘肽转移酶和NAD(P)H：苯醌还原酶，从而使第一相酶产生的任何残留亲电代谢物解毒，从而摧毁它们损伤DNA的能力。由于异硫氰酸酯通过双重机制阻止癌症的发生，并且已经大量存在于人类饮食中，这些试剂是开发有效的人类抗癌化学保护的理想候选者。
Organic isothiocyanates block the production of tumors induced in rodents by diverse carcinogens (polycyclic aromatic hydrocarbons, azo dyes, ethionine, N-2-fluorenylacetamide, and nitrosamines). Protection is afforded by alpha-naphthyl-, beta-naphthyl-, phenyl-, benzyl-, phenethyl-, and other arylalkyl isothiocyanates against tumor development in liver, lung, mammary gland, forestomach, and esophagus. Many isothiocyanates and their glucosinolate precursors (beta-thioglucoside, N-hydroxysulfate) occur naturally and sometimes abundantly in plants consumed by humans, e.g., cruciferous vegetables. Nevertheless, the possible contributions of isothiocyanates and glucosinolates to the well recognized protective effects against cancer of high consumptions of vegetables are unclear. The anticarcinogenic effects of isothiocyanates appear to be mediated by tandem and cooperating mechanisms: (a) suppression of carcinogen activation by cytochromes P-450, probably by a combination of down-regulation of enzyme levels and direct inhibition of their catalytic activities, which thereby lower the levels of ultimate carcinogens formed; and (b) induction of Phase 2 enzymes such as glutathione transferases and NAD(P)H: quinone reductase, which detoxify any residual electrophilic metabolites generated by Phase 1 enzymes and thereby destroy their ability to damage DNA. Since isothiocyanates block carcinogenesis by dual mechanisms and are already present in substantial quantities in human diets, these agents are ideal candidates for the development of effective chemoprotection of humans against cancer.