• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4809-4813
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5117-5121
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• 2014

Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

• 대한의생명과학회지
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• 제9권1호
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• pp.51-58
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• 2003

This study was carried out to investigate the preventive and therapeutic effect of Panax ginseng water extract (PG-WE) on the toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), one of the most notorious toxic environmental pollutants belonging to the group of polyhalogenated aromatic hydrocarbons. Normal control (NC) group guinea pigs (180~200 g) received vehicle and saline, and TCDD-treated (TT) group was given TCDD and saline. P100 and P200 group animals received PG-WE for 28 days since 1 week before TCDD exposure at daily doses of 100 mg/kg b.w. and/or 200 mg/kg b.w., respectively. C100 and C200 group received PG-WE for 14 days starting 1 week after TCDD-exposure. Toxicity was induced by a single intraperitoneal injection of TCDD (1 $\mu\textrm{g}$/kg b.w.). Abnormal increase in AST and ALT activities in TT group was significantly improved by the administration of PC-WE. Microscopically, there were mild to moderate swelling of hepatocytes, hyperchromatism of individual cells, acidophilic cytoplasm and cytoplasm vacuolation of some hepatocytes, slight to moderate variations of staining density, occasional single cell necrosis, variable size and shape of some hepatocytes, small groups of degenerating hepatocytes surrounded by mononuclear cells, dilated sinusoids of centrilobular zone and some loss of lobular architecture in TT group liver. From these results, we could find the protective and therapeutic role of PG-WE in TCDD-induced liver toxicity by examining the blood chemical parameters and histopathological observation.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.118.1-118.1
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• 2003

A growing body of scientific research indicates that man-made chemicals (xenobiotics) may interfere with the normal functioning of endocrine, or hormone systems. These endocrine disruptors may cause a variety of problems with development, behavior, and reproduction. Amongst the xenobiotics the World Health Organization classed 2, 3, 7, 8-TCDD as a "known" human carcinogen. (omitted)

• 한국환경성돌연변이발암원학회지
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• 제24권4호
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• pp.163-170
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• 2004

CYP1B1 enzyme metabolize PAHs and estradiol. CYP1B1 metabolize estradiol to 4-hydroxyestradiol that is considered as carcinogenic metabolite. Luciferase activity was induced about 20 folds over that control by 1 nM TCDD (2,3,7,8-tetrchlorodibenzo-p-dioxin) and these inductions were dose-dependent. Recent industrialized society, human hasbeen widely been exposed to widespread environmental contaminants such as PAHs (polycyclic aromatic hydrocarbon) that are originated from the incomplete combustion of hydrocarbons. PAHs are known to be ligands of the AhR (aryl hydrocarbon receptor). Induction of cytochrome P4501B1(CYP1B1) in cell culture is widely used as a biomarket for PAHs. Therefore we have studied the effect of PAHs in the human breast cancer cells MCF-7 to evaluate bioactivity of PAHs. Cytochrome P4501B1(CYP1B1) is known to be inducible by xenobiotic compounda such as policyclic aromatic hydrocarbon (PAH) and dioxins such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD). And these induction of CYP1B1 is also regulated by many categories of chemicals. In order to investigate the effects of several chemicals on CYP1B1 gene expression in luciferase gene, and then transfected into these cells. After treatment of chemicals, the luciferase activity was measured. We examined effects of PAHs on the CYP1B1-lucifrease reporter gene and CYP1B1 mRNA level. Benzo(k)fluoranthene showed strong response to CYP1B1 promoter activity stimulation, and also CYP1B1 mRNAs increase in MCF-7 cells in a concentration-dependent manner. flvonoids such as genistein decreased B(k)F induced luciferase activity at low concentration. it exhibited stimulatory effect at high concentration.

• 동의생리병리학회지
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• 제18권5호
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• pp.1410-1417
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• 2004

To evaluate effect of Gamimajeonojahwan(GMOH) water extract on sexual functions, we orally administered GMOH exract(1,100㎎/㎏) for four weeks in male rats impaired by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and ketoconazole(KZ). And we investigated the sexual behaviors such as mount latency, mount frequency, intromission latency, intromission frequency, ejaculation period and ejaculation latency. Serum testosterone concentrations also are evaluated in GMOH-and/or vehicle-treated male rats. The results were obtained as follows: GMOH inhibited the increase of intromission latency by TCDD in male rats. GMOH inhibited the decrease of intromission frequency by TCDD in male rats. GMOH inhibited the increase of ejaculation latency by TCDD in male rats. GMOH inhibited the decrease of serum testosterone concentration by TCDD in male rats. GMOH inhibited the decrease of serum testosterone concentration by KZ in male rats. These results suggest that GMOH water extract is active in improving sexual functions and protecting a decrease of testosterone concentrations induced by TCDD and KZ in male rats.

• Tuberculosis and Respiratory Diseases
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• 제78권2호
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• pp.99-105
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• 2015

Background: Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues. Methods: BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction. Results: The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines. Conclusion: Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions.

• 생명과학회지
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• 제13권4호
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• pp.457-462
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• 2003

TCDD를 투여한지 일주일 후부터 어성초를 200mg/kg 복강 내로 4주간 격일로 투여하였다. TTA군과 NTT군은 saline을 투여하였다. 혈청에서 GOT, GPT의 활성도를 측정하였고, 간조직중에서 MDA, GSH, GSSG, GPx, SOD, Catalase의 level을 측정하였다. GOT 활성도는 HTT군이 TTA군과 비교해서 49.00%의 억제 효과를 보였다. 반면 GPT활성도는 TTA(29.70)군에 비해 68.36%의 억제효과를 보였다. MDA는 TTA군이 NTT군 보다 높게 나왔으며, HTT군은 NTT군에 비교하여 30.47%의 억제율을 보였다. HTT군의 GSH는 TTA군에 비해 1.91배 증가하였고, GSSG는 TTA군에 비해 46.72% 감소하였다. SOD는 TTA군이 NTT군보다 낮게 나타났고, HTT는 TTA군에 비해 46%의 증가를 보였다. Catalase는 TTA군(1.12mU/mg protein)의 활성은 NTT(3.44mU/mg protein)군 보다 32.56% 감소하였다. HTT군의 간의 Catalase 활성도는 TTA 군과 비교하여 50.00% 증가 하였다. 이러한 결과에서 보듯이 TCDD로 인해 생성된 free radical은 항산화 효소에 의해서 감소되었으며, 그리고 어성초가 항산화 효소 대신에 노화를 저해하는 작용을 하는 것으로 사료 된다.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2001년도 학술대회
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• pp.115-116
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• 2001

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.125-125
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• 2002