Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context.
Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context.
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DOI：
10.1289/ehp.6322
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发表时间：
2003-12
影响因子：
10.4
通讯作者：
Safe SH
中科院分区：
文献类型：
--
作者：
Zhang S;Qin C;Safe SH
化学保护性植物化学物质具有多种活性，并与几种细胞受体相互作用，包括芳烃（Ah）受体（AhR）。在这项研究中，我们研究了AhR激动剂/拮抗剂活性的黄酮类化合物：白杨素，根皮素，山奈酚，高良姜，柚皮素，染料木素，槲皮素，杨梅素，木犀草素，黄芩素，大豆苷元，芹菜素，地奥司明。我们还研究了AhR依赖的活性，黄芩苷和大黄素（在草药提取物）在Ah-responsive MCF-7人乳腺细胞，HepG 2人肝癌细胞，和小鼠Hepa-1细胞瞬时或稳定转染表达荧光素酶报告基因连接到多个拷贝的共识二恶英响应元件的质粒。AhR激动剂活性的化合物（1和10微M）高达25%的最大反应诱导的5 nM的2，3，7，8-四氯二苯并-p-二恶英（TCDD），其效力依赖于细胞环境。高良姜素、染料木素、大豆苷元和地奥司明仅在Hepa-1细胞中有活性，而芫荽苷仅在人HepG 2和MCF-7细胞中诱导活性。Western blot分析证实黄芩素和大黄素也诱导人癌细胞系中的CYP 1A 1蛋白。还研究了在MCF-7和HepG 2细胞中作为激动剂无活性的四种化合物（山奈酚、槲皮素、杨梅素和木犀草素）的AhR拮抗剂活性。木犀草素是一种AhR拮抗剂，在这两种细胞系中，和其他化合物的抑制作用依赖于细胞环境。这些数据表明，膳食植物化学物质表现出大量的细胞环境依赖性AhR激动剂以及拮抗剂活性。此外，由于食物中的植物化学物质和其他具有AhR活性的化合物在饮食中的浓度相对较高，因此，对饮食中毒性当量的四氯二苯并对二恶英和相关化合物的风险评估也应考虑到植物化学物质的AhR激动剂/拮抗剂活性。
Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon (Ah) receptor (AhR). In this study we investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin. We also investigated the AhR-dependent activities of cantharidin and emodin (in herbal extracts) in Ah-responsive MCF-7 human breast cells, HepG2 human liver cancer cells, and mouse Hepa-1 cells transiently or stably transfected with plasmids expressing a luciferase reporter gene linked to multiple copies of a consensus dioxin-responsive element. The AhR agonist activities of the compounds (1 and 10 micro M) were as high as 25% of the maximal response induced by 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their potencies were dependent on cell context. Galangin, genistein, daidzein, and diosmin were active only in Hepa-1 cells, and cantharidin induced activity only in human HepG2 and MCF-7 cells. Western blot analysis confirmed that baicalein and emodin also induced CYP1A1 protein in the human cancer cell lines. The AhR antagonist activities of four compounds inactive as agonists in MCF-7 and HepG2 cells (kaempferol, quercetin, myricetin, and luteolin) were also investigated. Luteolin was an AhR antagonist in both cell lines, and the inhibitory effects of the other compound were dependent on cell context. These data suggest that dietary phytochemicals exhibit substantial cell context-dependent AhR agonist as well as antagonist activities. Moreover, because phytochemicals and other AhR-active compounds in food are present in the diet at relatively high concentrations, risk assessment of dietary toxic equivalents of TCDD and related compounds should also take into account AhR agonist/antagonist activities of phytochemicals.
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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：
8.8
作者：
AHLBORG, UG;BECKING, GC;YRJANHEIKKI, E
通讯作者：
YRJANHEIKKI, E
影响因子：
5.8
作者：
Chen, I;Safe, S;Bjeldanes, L
通讯作者：
Bjeldanes, L
影响因子：
3.6
作者：
Quadri, SA;Qadri, AN;Sherr, DH
通讯作者：
Sherr, DH
影响因子：
5.8
作者：
Gradelet, S;Astorg, P;Lesca, P
通讯作者：
Lesca, P