Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane.
Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane.
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DOI：
10.3389/fnut.2021.734334
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发表时间：
2021
影响因子：
5
通讯作者：
Williams DE
中科院分区：
文献类型：
--
作者：
Williams DE
植物或细菌黑芥子酶水解芸苔素会产生多种吲哚，主要是吲哚-3-甲醇 (I3C)。 I3C 及其主要体内产品 3,3'-二吲哚基甲烷 (DIM) 在临床前模型中是有效的癌症化学预防剂，并在临床试验中显示出前景。 DIM 的药代动力学/药效学已在啮齿类动物和人类中进行了研究，尿液 DIM 是十字花科蔬菜膳食摄入量的拟议生物标志物。俄勒冈州立大学最近的临床研究表明，DIM 在体内通过单羟基化和双羟基化，然后与硫酸盐或葡萄糖醛酸结合，具有惊人的强大代谢能力。 DIM 具有多种作用机制，最典型的是调节芳烃受体 (AHR) 信号传导。在虹鳟鱼中，当在黄曲霉毒素 B1、多环芳烃、亚硝胺或直接作用致癌物（如 N-甲基-N'-硝基亚硝基胍）之前或同时给予时，可以通过膳食 I3C 实现剂量依赖性癌症化学预防。喂养怀孕小鼠 I3C 可抑制经胎盘致癌。在人类中，主要关注点是乳腺癌和前列腺癌的化学预防。细胞色素 P450 依赖性雌激素代谢的改变被认为是 DIM 依赖性乳腺癌预防的重要驱动因素。迄今为止进行的少数几项研究将富含葡萄糖苷的十字花科植物（例如抱子甘蓝）与 I3C/DIM 补充剂进行比较，结果表明后者的更大影响归因于剂量。每天需要摄入公斤量的球芽甘蓝才能产生可通过补充剂达到的体内 DIM 水平。在临床试验中，这些补充剂剂量几乎没有引起任何副作用。来自萝卜硫苷的萝卜硫素可以与芥子苷衍生的 DIM 协同作用，这可能为临床上组合方法（补充剂和食物）带来机会。
Hydrolysis of glucobrassicin by plant or bacterial myrosinase produces multiple indoles predominantly indole-3-carbinol (I3C). I3C and its major in vivo product, 3,3'-diindolylmethane (DIM), are effective cancer chemopreventive agents in pre-clinical models and show promise in clinical trials. The pharmacokinetics/pharmacodynamics of DIM have been studied in both rodents and humans and urinary DIM is a proposed biomarker of dietary intake of cruciferous vegetables. Recent clinical studies at Oregon State University show surprisingly robust metabolism of DIM in vivo with mono- and di-hydroxylation followed by conjugation with sulfate or glucuronic acid. DIM has multiple mechanisms of action, the most well-characterized is modulation of aryl hydrocarbon receptor (AHR) signaling. In rainbow trout dose-dependent cancer chemoprevention by dietary I3C is achieved when given prior to or concurrent with aflatoxin B1, polycyclic aromatic hydrocarbons, nitrosamines or direct acting carcinogens such as N-methyl-N'-nitro-nitrosoguanidine. Feeding pregnant mice I3C inhibits transplacental carcinogenesis. In humans much of the focus has been on chemoprevention of breast and prostate cancer. Alteration of cytochrome P450-dependent estrogen metabolism is hypothesized to be an important driver of DIM-dependent breast cancer prevention. The few studies done to date comparing glucobrassicin-rich crucifers such as Brussels sprouts with I3C/DIM supplements have shown the greater impact of the latter is due to dose. Daily ingestion of kg quantities of Brussels sprouts is required to produce in vivo levels of DIM achievable by supplementation. In clinical trials these supplement doses have elicited few if any adverse effects. Sulforaphane from glucoraphanin can act synergistically with glucobrassicin-derived DIM and this may lead to opportunities for combinatorial approaches (supplement and food-based) in the clinic.
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影响因子：
6.1
作者：
Busbee PB;Rouse M;Nagarkatti M;Nagarkatti PS
通讯作者：
Nagarkatti PS
影响因子：
3.8
作者：
Beaver, Laura M.;Yu, Tian-Wei;Ho, Emily
通讯作者：
Ho, Emily
DOI：
10.1073/pnas.88.21.9543
发表时间：
1991-11-01
影响因子：
11.1
作者：
BJELDANES, LF;KIM, JY;BRADFIELD, CA
通讯作者：
BRADFIELD, CA
影响因子：
4.1
作者：
Bailey, George S.;Reddy, Ashok P.;Swenberg, James A.
通讯作者：
Swenberg, James A.
DOI：
10.1186/s13167-015-0048-9
发表时间：
2015
期刊：
The EPMA journal
影响因子：
--
作者：
Ashrafian L;Sukhikh G;Kiselev V;Paltsev M;Drukh V;Kuznetsov I;Muyzhnek E;Apolikhina I;Andrianova E
通讯作者：
Andrianova E