Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells
Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells
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DOI：
10.1016/0006-2952(96)00060-3
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发表时间：
1996-04-26
影响因子：
5.8
通讯作者：
Bjeldanes, L
中科院分区：
文献类型：
--
作者：
Chen, I;Safe, S;Bjeldanes, L
吲哚-3-甲醇（13 C）是芸苔属蔬菜的主要成分，二吲哚甲烷（DIM）是13 C酸催化缩合的主要产物。这两种化合物以相对低的亲和力竞争性地结合到芳基烃（Ah）受体。在Ah-responsive T47 D人乳腺癌细胞中，I3 C和DIM分别在高达125或31 μ M的浓度下未诱导显著的CYP 1A 1依赖性乙氧基试卤灵O-脱乙基酶（EROD）活性或CYP 1A 1 mRNA水平。1 nM浓度的2，3，7，8-四氯二苯并-p-二恶英（TCDD）诱导这些细胞中的EROD活性，TCDD与不同浓度的I3 C联合处理（1-125 μ M）或DIM（1-31 μ M）导致在最高浓度的I3 C或DIM下诱导的反应降低> 90%。I3 C或DIM也部分抑制（< 50%）通过TCDD和报告基因活性诱导CYP 1A 1 mRNA水平，在瞬时转染试验中使用Ah应答质粒构建体。在T47 D细胞中，单独用5 nM [H-3]TCDD或与250 μ M I3 C或31 μ M DIM联合处理，细胞核Ah受体的形成分别减少37%和73%。I3 C和DIM对诱导的EROD活性的更有效抑制是由于体外抑制酶活性。因此，I3 C和DIM都是T47 D人乳腺癌细胞系中的部分Ah受体拮抗剂。
Indole-3-carbinol (I3C) is a major; component of Brassica vegetables, and diindolylmethane (DIM) is the major acid-catalyzed condensation produce derived from 13C. Both compounds competitively bind to the aryl hydrocarbon (Ah) receptor with relatively low affinity. In Ah-responsive T47D human breast cancer cells, I3C and DIM did not induce significantly CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity or CYP1A1 mRNA levels at concentrations as high as 125 or 31 mu M, respectively. A 1 nM concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced EROD activity in these cells, and cotreatment with TCDD plus different concentrations of I3C (1-125 mu M) or DIM (1-31 mu M) resulted in a > 90% decrease in the induced response at the highest concentration of I3C or DIM. I3C or DIM also partially inhibited (< 50%) induction of CYP1A1 mRNA levels by TCDD and reporter gene activity, using an Ah responsive plasmid construct in transient transfection assays. In T47D cells cotreated with 5 nM [H-3]TCDD alone or in combination with 250 mu M I3C or 31 mu M DIM, there was a 37 and 73% decrease, respectively, in formation of the nuclear Ah receptor. The more effective inhibition of induced EROD activity by I3C and DIM was due to in vitro inhibition of enzyme activity. Thus, both I3C and DIM are partial Ah receptor antagonists in the T47D human breast cancer cell line.