Cornblatt Brian S, Ye Lingxiang, Dinkova-Kostova Albena T, Erb Melanie, Fahey Jed W, Singh Navin K, Chen Min-Shue A, Stierer Tracey, Garrett-Mayer Elizabeth, Argani Pedram, Davidson Nancy E, Talalay Paul, Kensler Thomas W, Visvanathan Kala
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Carcinogenesis. 2007 Jul;28(7):1485-90. doi: 10.1093/carcin/bgm049. Epub 2007 Mar 7.
Consumers of higher levels of Brassica vegetables, particularly those of the genus Brassica (broccoli, Brussels sprouts and cabbage), reduce their susceptibility to cancer at a variety of organ sites. Brassica vegetables contain high concentrations of glucosinolates that can be hydrolyzed by the plant enzyme, myrosinase, or intestinal microflora to isothiocyanates, potent inducers of cytoprotective enzymes and inhibitors of carcinogenesis. Oral administration of either the isothiocyanate, sulforaphane, or its glucosinolate precursor, glucoraphanin, inhibits mammary carcinogenesis in rats treated with 7,12-dimethylbenz[a]anthracene. In this study, we sought to determine whether sulforaphane exerts a direct chemopreventive action on animal and human mammary tissue. The pharmacokinetics and pharmacodynamics of a single 150 mumol oral dose of sulforaphane were evaluated in the rat mammary gland. We detected sulforaphane metabolites at concentrations known to alter gene expression in cell culture. Elevated cytoprotective NAD(P)H:quinone oxidoreductase (NQO1) and heme oxygenase-1 (HO-1) gene transcripts were measured using quantitative real-time polymerase chain reaction. An observed 3-fold increase in NQO1 enzymatic activity, as well as 4-fold elevated immunostaining of HO-1 in rat mammary epithelium, provides strong evidence of a pronounced pharmacodynamic action of sulforaphane. In a subsequent pilot study, eight healthy women undergoing reduction mammoplasty were given a single dose of a broccoli sprout preparation containing 200 mumol of sulforaphane. Following oral dosing, sulforaphane metabolites were readily measurable in human breast tissue enriched for epithelial cells. These findings provide a strong rationale for evaluating the protective effects of a broccoli sprout preparation in clinical trials of women at risk for breast cancer.
食用较多十字花科蔬菜，尤其是十字花科属（西兰花、抱子甘蓝和卷心菜）蔬菜的人群，对多种器官部位癌症的易感性会降低。十字花科蔬菜含有高浓度的硫代葡萄糖苷，其可被植物酶黑芥子酶或肠道微生物群水解为异硫氰酸盐，而异硫氰酸盐是细胞保护酶的有效诱导剂和致癌作用的抑制剂。口服异硫氰酸盐萝卜硫素或其硫代葡萄糖苷前体葡萄糖萝卜硫苷，可抑制经7,12 - 二甲基苯并[a]蒽处理的大鼠的乳腺癌发生。在本研究中，我们试图确定萝卜硫素是否对动物和人类乳腺组织发挥直接的化学预防作用。在大鼠乳腺中评估了单次口服150 μmol萝卜硫素剂量的药代动力学和药效学。我们检测到萝卜硫素代谢物的浓度已知可在细胞培养中改变基因表达。使用定量实时聚合酶链反应测量细胞保护酶NAD(P)H：醌氧化还原酶（NQO1）和血红素加氧酶-1（HO-1）基因转录本的升高情况。观察到大鼠乳腺上皮细胞中NQO1酶活性增加了3倍，以及HO-1免疫染色升高了4倍，这为萝卜硫素显著的药效学作用提供了有力证据。在随后的一项初步研究中，八名接受缩乳术的健康女性服用了一剂含有200 μmol萝卜硫素的西兰花芽提取物。口服给药后，在富含上皮细胞的人乳腺组织中很容易检测到萝卜硫素代谢物。这些发现为在乳腺癌风险女性的临床试验中评估西兰花芽提取物的保护作用提供了有力的理论依据。
