• Proceedings of the PSK Conference
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• 2003.10b
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• pp.131.1-131.1
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• 2003

Phytoestrogens are naturally occurring compounds derived from plants. Structurally, some phytoestrogens resemble endogenous estrogen of humans and animals. Phytoestrogens exhibit estrogen agonist/antagonist properties and have many biological effects such as prevention of hormone-dependent breast cancer, anti-oxidative activity, inhibition of tyrosine kinase activities and inhibition of angiogenesis. In this study we investigated whether biochanin A, a phytoestrogen, and its metabolites such genistein, p-ethylphenol and phenolic aic affect IL-4 production in EL-4 thymoma cell-line and primary lymph node cells. (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.107-107
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• 1997

Cytochrome P450 enzymes have been intensively investigated in hepatic tissues and several mammalian cell lines. Compared to most studies about cytochrome P450 isozymes in liver in vivo and hepatic, cell lines in vitro, the study of cytochrome P450IA1 in human breast cancer cells could be very important to understand the mechanism of the regulation of CYPIA1 gene expression and cell growth. MCF-7 human breast cancer cells are well characterized to study estrogen and antiestrogen action due to the fact that they contain high level of estrogen receptor and have biological markers characterized. And also MCF-7 cells express high level of arylhydrocarbon hydroxylase activity and human cytochrome P450IA1 cDNA was cloned from MCF-7 cells. Ah receptor was characterized in many breast cancer cell lines and polycyclic aromatic hydrocarbon such as 3-MC induced the expression of CYPIA1 gene and cytochrome P450- dependent monooxygenase activity. We undertook a study to examine the effect of estrogens and other chemicals on the regulation of human CYPIA1 gene expression in MCF-7 cells via RTPCR analysis, that might help us to understand the mechanism of the regulation of CYPIA1 gene expression and MCF-7 cell growth. Expression vector containing the functional 5'-regulatory region of human CYPIA1 fused to the CAT reporter gene was transfected into estrogen receptor positive MCF-T cells or estrogen receptor negative MDA-MB-231 cells. After these cells were treated with various chemicals, RTPCR was carried out to measure both CYPIA1 mRNA and CAT mRNA levels. 1nM 3-MC increased in both P450 and CAT mRNA levels over those of control by two folds in MCF-7 cells but does not in MDA-MB-231 cells. Estrogen or tamoxifen or retinoic acid or chrysin decreased in both P450 and CAT mRNA levels that were induced by 3-MC in MCF-7 when each chemical was administered with 3-MC concomitantly. These results suggested that the level of CYPIA1 gene expression is modulated with estrogen-related molecules and make it possible to speculate that ER is related to CYPIA1 gene expression and cell growth in breast cancer cells. [Supported by grants from the Korean Ministry of Education ]

• Korean Journal of Pharmacognosy
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• v.52 no.2
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• pp.118-125
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• 2021

Leguminosae plants are known for its phytoestrogen constituents which play a major role in the prevention of osteoporosis, cancer and heart disease. In this study, the estrogenic activity of 158 samples from 58 species, 3 subspecies and 10 varieties of Leguminosae plants growing in Korea was evaluated. An estrogen, 17β-estradiol was used as a reference compound, and the potency of each sample was expressed in relative efficacy (%) compared to that of the reference by a reporter gene assay using MCF-7 cells. As results, the estrogenic activity of methanolic extracts of Phaseolus vulgaris var. humilis, Sophora flavescens, Lespedeza × robusta, Indigofera pseudotinctoria, Maackia amurensis, Glycine soja, Wisteria floribunda, Robinia pseudoacacia, Astragalus sinicus, Pueraria lobata, Lespedeza maximowiczii var. tomentella, Trifolium repens and Crotalaria sessiliflora showed similar to or higher at 100 ㎍/ml than the positive control at 10 nM. These findings can be a potential evidence for developing estrogen alternatives resolving various types of menopause symptoms with information on proper harvest season and usage plant part. To the best of our knowledge, the estrogenic activity of Lespedeza × robusta, Indigofera pseudotinctoria, Wisteria floribunda, Robinia pseudoacacia and Lespedeza maximowiczii var. tomentella is reported for the first time in this study.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.135-135
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• 2003

Bisphenol A (BPA) mimics estrogen and its activity is one third to one quarter that of estradiol. BPA, an ubiquitous environmental contaminent has been shown to cause development reproductive toxicity and carcinogenic effect. BPA may do physiological action through ER${\alpha}$ and ER${\beta}$ which are expressed in central nerve system.(omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.112-112
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• 2001

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells. In the present study, we have examined the effect of natural estrogen, phytoestrognes and environmental estrogens on the regulation of CYP1A1 gene expression in MCF-7 human breast cancer cell line. that ER and AhR are co-expressed. pCYP1A1 -luc reporter gene was transiently transfected into MCF-7 cells. These cells were treated with various chemicals and then luciferase assay was carried out. 17be1a-estradiol significantly inhibited TCDD stimulated luciferase activity dose dependently and this inhibition was partially recovered by concomitant treatment of tamoxifen. 17beta-estradiol metabolites, 2-hydroxyestradiol and 16alpha-estriol resulted in less potent inhibitory effect than estradiol and synthetic estrogen, diethylstilbestrol (DES) showed no effect on CYP1A1 gene expression. This study demonstrated that estrogen down-regulated TCDD stimulated CYP1A1 expression via ER mediation. And we have found out that several flavonoids such as genistein, kaempferol, daidzein, naringenin, and alkylphenols such as nonylphenol, 4-octylphenol and resveratrol also inhibited TCDD induced CYP1A1 expression like estrogen.

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.175-182
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• 2002

Endocrine disruptors (EDs) are the chemicals that affect endocrine systems through activation or inhibition of steroid hormone response. It is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. The key targets of EDs are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. We constructed a co-expression system of Gal4p DNA binding domain (DBD)- ligand binding domain of human estrogen receptor $\alpha$ or $\beta$, and Gal4p transactivation domain (TAD)-co-activator AIB-1, SRC-1 or TIF-2 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and Gal4p binding site (GAL4 upstream activating sequence, GAL4$_{UAS}$). Expression of this reporter gene was dependent on the presence of estrogen or EDs in the culture medium. We found that the two-hybrid system with combination of the hER$\beta$ LBD and co-activator SRC-1 was most effective in the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. The data in this research demonstrated that the yeast detection system using steroid hormone receptor and co-activator is a useful tool for identifying chemicals that interact with steroid receptors.s.

• Journal of Aquaculture
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• v.17 no.1
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• pp.62-68
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• 2004

A cDNA encoding the masu salmon, Oncorhynchus masou, estrogen receptor $\alpha$ (msER$\alpha$) was cloned from the pituitary gland by polymerase chain reaction (PCR). This cDNA contains an open reading frame encoding 513 amino acid residues, and the calculated molecular weight of this protein is about 56,430 Dalton. The amino acid sequences of the DNA binding and ligand binding domains of msER$\alpha$ showed high homology to those of other fish species (84-100%). Reverse transcription PCR analysis showed that the mRNA level of msER$\alpha$ in the pituitary was slightly higher in estradiol-17$\beta$(E2) injected masu salmon than that of control fish. To test the biological activity of msER$\alpha$, the cDNA was ligated to a mammalian expression vector and transfected into a gonadotrope-derived cell line, L$\beta$T2, with a reporter plasmid including estrogen responsive element. Expression of the reporter protein, luciferase, was E2 and msER$\alpha$-dependent. The masu salmon ER$\alpha$ is structurally conserved among teleost species and functions as a transcriptional activator in the pituitary cells.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1051-1054
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• 2013

Closo-carborane has been considered as an efficient boron-carrier for boron neutron capture therapy (BNCT) and an attractive surrogate of lipophilic phenyl or cyclohexyl ring in drug design. Despite a great number of carborane-containing ligands have been synthesized and evaluated, molecular modeling studies of carborane ligands with macromolecules have been rarely reported. We herein describe a facile docking and scoring-function strategy of 16 carborane ligands with an estrogen receptor by using the commercial Gaussian, Chem3D Pro and Discovery Studio (DS) computational programs. Docked poses of the carborane ligands in silico exhibited similar binding modes to that of the crystal ligand in the active site of estrogen receptor. Score analysis of the best docked pose for each ligand indicated that the Ligscore1 and the Dockscore have a moderate correlation with in vitro biological activity. This is the first report on the scoring-correlation studies of carborane ligands with macromolecules. The integrated Gaussian-DS approach has a potential application for virtual screening, De novo design, and optimization of carborane ligands in medicinal chemistry.

• Natural Product Sciences
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• v.11 no.4
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• pp.220-224
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• 2005

Extensive chemical studies on the stem bark extracts of two Guttifereous plants namely Mesua daphnifolia and Garcinia nitida have led to the isolation of eight xanthones. Mesua daphnifolia gave cudraxanthone G (1), ananixanthone (2), 1,3,5-trihydroxy-4-methoxyxanthone (3) and euxanthone (4) while Garcinia nitida gave inophyllin B (5), 1,3,7-trihydroxy-2,4-bis (3-methylbut-2-enyl)xanthone (6), 3-isomangostin (7) and rubraxanthone (8). All these compounds were assayed against the MDA-MB-231 (human estrogen receptor negative breast cancer) cells. A structure-activity relationship study showed that structurally, all the 1, 3-oxygenated xanthones which carried unsaturated prenyl side chains (either 3-methylbut-2-enyl or 1,1-dimethyl-2-propenyl) at carbones C-2 and C-4 in the xanthone ring A are essential for the outstanding activities in the assay.

• The Journal of Korean Medicine
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• v.22 no.4
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• pp.1-9
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• 2001

Objectives : To investigate the effect of Taxilli Ramulus (TR) extract on bone metabolism of ethanol-treated animal model. Methods : The changes of serum calcium, calcitonin, estrogen level, a1ka1ine phosphatase activity, osteocalcin, parathyroid hormone content and urine calcium level were observed with ethanol treatment for 60 days. The results were compared with an ethanol- TR extract double treatment group. Results : We observed increment of serum osteocalcin, parathyroid hormone content, alkaline phosphatase activity and urine calcium level by chronic ethanol feed and they were recovered to near normal level with Taxilli Ramulus extract treatment. Weight gain, serum calcium level, calcitonin and estrogen content were remarkably reduced with ethanol treatment and their levels were normalized by Taxilli Ramulus extract. Conclusions : These results showed that Taxilli Ramulus extract have the ability to recover to normal in the body an abnormal calcium metabolism process due to external factors. These results suggested that Taxilli Ramulus extract have preventive effects on calcium concentration loss and osteoporosis.