• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5801-5805
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• 2015

As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several pathophysiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.119.2-119.2
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• 2003

Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CYP1A1 gene. Retinoic acid (RA) regulates the transcription of various genes for several essential functions through binding to two classes of nuclear receptors, the retinoic acid receptor (RAR) and retinoid X receptor (RXR). (omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.90-105
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• 2002

The dioxin- or aryl hydrocarbon receptor (AhR) is a member of the Per-Arnt-Sim family of nuclear transcription factors exhibiting a basic helix-loop-helix structure. In its non-ligated state the AhR is associated with hsp 90 and the immunophilin-type XAP2. Upon ligand binding the associated proteins are released, the receptor dimerizes with the AhR nuclear trans locator protein Arnt, and binds to XREs (xenobiotic-responsive elements) in the 5'-flanking region of responsive genes thus modulating their transcription.(omitted)

• 디지털융복합연구
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• 제17권1호
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• pp.443-447
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• 2019

방향성탄화수소 수용체(Arylhydrocarbon Receptor, AhR)은 리간드에 의해 활성화되어 체내 외래물질의 대사를 조절하는 전사인자다. 생체 내에서 AhR의 생리학적 역할은 오랜 기간 연구되어 왔으나 활성화를 유발하지 않는 길항제를 비롯하여 유효한 화학적 도구가 아직 개발되지 않아 기능 연구가 제한적이다. AhR이 다양한 질병의 발병기전에서 중요한 역할을 수행한다는 것이 보고됨에 따라 약물 표적으로서 유효하다고 판단되나 치료나 예방을 위한 유효한 약물은 아직 개발되지 않았다. 길항제로 알려진 화합물들은 낮은 농도에서는 활성이 있어 연구 목적으로 활용되고 있으나 높은 농도에서는 방향성 탄화수소를 활성화하는 부분적 agonist로 작용한다. 이에 AhR 활성화를 유도하지 않는 순수한 길항제의 개발이 필요하다. 본 연구에서는 이미 알려진 AhR 길항제의 골격인 phenyldiazenylphenylpicolinamide의 세 고리구조 중 두 고리구조에 존재하는 메틸 기들을 변형하여 활성을 평가하는 구조-활성 관계 연구를 통하여 새로운 길항제를 개발하고자 하였다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.136-136
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• 2003

Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CVP1A1 gene.(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.23-23
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• 2003

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon (AhR) ligands suppress 17${\beta}$-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent degradation of endogenous estrogen receptor ${\alpha}$ (ER${\alpha}$).(omitted)

• Toxicological Research
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• 제23권2호
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• pp.135-142
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• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.

• BMB Reports
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• 제32권3호
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• pp.279-287
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• 1999

The aromatic hydrocarbon receptor (AhR) is a cytosolic protein that binds the environmental pollutant, dioxin. The liganded AhR translocates into the nucleus where it heterimerizes with a constitutive nuclear protein, AhR nuclear translocator (Arnt). The N-terminal regions of both AhR and Arnt contain basic helix-loop-helix (bHLH) and Per-AhR-Arnt-Sim (PAS) motifs that are required for DNA binding, dimerization, and ligand binding whereas the C-terminal regions of both AhR and Arnt contain transactivation domains. Here, results from the mammalian two-hybrid system indicate that Arnt can make a homodimer but AhR cannot. In the presence of dioxin, the interaction between AhR and Arnt is stronger than that of the Arnt homodimer, suggesting that Arnt prefers to make a heterodimer with the liganded AhR rather than a homodimer. Transfection analyses using the GAL4-driven reporter system suggest that AhR's N-terminal region represses its own transactivation domain, as well as exogenous transactivation domains such as Sp 1 and VP16. Interestingly, the repressed transactivation domains of AhR are activated by ligand-dependent heterodimerization with Arnt. These observations suggest that heterodimerzation with Arnt is necessary not only for DNA binding but also for activation of the repressed transactivation capability of AhR.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.23-23
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• 2003

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.89-89
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• 2003

Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CYP1A1 gene. Retinoic acid (RA) regulates the transcription of various genes for several essential functions through binding to two classes of nuclear receptors, the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Constitutive androstane receptor (CAR) also regulates the transcription of gene. In this study, we have examined how RAR, RXR and CAR regulated CYP1A1 in rainbow trout hepatoma cell (RTH 149) using luciferase reporter gene assay system. We did transient transfection with CYP1A1 luciferase reporter gene and treated with TCDD, all-trans RA, 9-cis RA and phenobarbital. Treatment of all-trans RA, 9-cis RA or phenobarbital decreased the TCDD induced transcription of CYP1Al. When we did transient cotransfection with CYP1A1 luciferase reporter gene and RXR, as increase of RXR concentration, the TCDD induced transcription of CYP1A1 was decreased. Transfection with CAR also decreased the TCDD induced transcription of CYP1A1 in RTH 149 cells.