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节俭型化学预防:用富含萝卜硫素的食物靶向激活核因子E2相关因子2(Nrf2)

Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane.

作者信息

Yang Li, Palliyaguru Dushani L, Kensler Thomas W

机构信息

Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261.

出版信息

Semin Oncol. 2016 Feb;43(1):146-153. doi: 10.1053/j.seminoncol.2015.09.013. Epub 2015 Sep 8.

Abstract

With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate produced by cruciferous vegetables such as broccoli, is found to be a highly promising chemoprevention agent against not only a variety of cancers such as breast, prostate, colon, skin, lung, stomach or bladder, but also cardiovascular disease, neurodegenerative diseases, and diabetes. For reasons of experimental exigency, preclinical studies have focused principally on sulforaphane itself, while clinical studies have relied on broccoli sprout preparations rich in either sulforaphane or its biogenic precursor, glucoraphanin. Substantive subsequent evaluation of sulforaphane pharmacokinetics and pharmacodynamics has been undertaken using either pure compound or food matrices. Sulforaphane affects multiple targets in cells. One key molecular mechanism of action for sulforaphane entails activation of the Nrf2-Keap1 signaling pathway although other actions contribute to the broad spectrum of efficacy in different animal models. This review summarizes the current status of pre-clinical chemoprevention studies with sulforaphane and highlights the progress and challenges for the application of foods rich in sulforaphane and/or glucoraphanin in the arena of clinical chemoprevention.

摘要

由于具有功效、安全性、耐受性、实用性和低成本等特性,含有生物活性植物化学物质的食物作为癌症化学预防策略的要素正受到广泛关注。萝卜硫素[1-异硫氰酸酯基-4-(甲基亚磺酰基)丁烷]是西兰花等十字花科蔬菜中天然存在的异硫氰酸酯,被发现不仅是一种对多种癌症(如乳腺癌、前列腺癌、结肠癌、皮肤癌、肺癌、胃癌或膀胱癌)具有高度潜力的化学预防剂,而且对心血管疾病、神经退行性疾病和糖尿病也有预防作用。出于实验紧迫性的原因,临床前研究主要集中在萝卜硫素本身,而临床研究则依赖于富含萝卜硫素或其生物前体葡萄糖异硫氰酸酯的西兰花芽提取物。随后使用纯化合物或食物基质对萝卜硫素的药代动力学和药效学进行了大量评估。萝卜硫素会影响细胞中的多个靶点。萝卜硫素的一个关键分子作用机制是激活Nrf2-Keap1信号通路,尽管其他作用也有助于其在不同动物模型中的广泛疗效。本综述总结了萝卜硫素临床前化学预防研究的现状,并强调了富含萝卜硫素和/或葡萄糖异硫氰酸酯的食物在临床化学预防领域应用的进展和挑战。

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