• 생약학회지
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• 제38권1호
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• pp.62-66
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• 2007

Ethanol extract from Salvia miltiorrhiza (SME) was tested for breast cancer chemoprevention and metastasis by measuring the activites of cytochrome P45O 1A1, aromatase, ornithine decarboxylase (ODC), and matrix metalloproteinase (MMP)-9. SME significantly inhibited cytochrome P45O 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity in a dose-dependent manner in a concentration range of 100${\sim}$l,200 ${\mu}g/ml$ (p<0.01). Microsomal aromatase (estrogen synthase) activity was suppressed 54.9%${\sim}$77.5% by the SME at concentration of 600${\sim}$l,200 ${\mu}g/ml$. ODC activity induced by 12-O-tet-radecanoylphorbol-13-acetate (TPA) was significantly reduced by the SME 900 and 1,200 ${\mu}g/ml$ (p<0.05) in MCF-7 breast cancer cells. In addition, SME (900 and 1,200 ${\mu}g/ml$) markedly inhibited MMP-9 activity, a key role in cancer metastasis. Therefore, SME is worth further investigation with respect to breast cancer chemoprevention or therapy.

• Environmental Analysis Health and Toxicology
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• 제31권
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• Journal of Microbiology and Biotechnology
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• 제16권9호
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• pp.1405-1409
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• 2006

Polysaccharides from the starfish Asterina pectinifera were assessed in vitro for their chemopreventive potential in human breast cancer. The polysaccharides from A. pectinifera inhibited cell proliferation in the estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. In addition, the polysaccharides were found to be an inhibitor of cytochrome P450 1A1-mediated ethoxyresorufin O-deethylase activity, and caused a dose-dependent inhibition of aromatase activity in microsomes isolated from a human placenta. There was a significant reduction in the ornithine decarboxylase activity to 30.7% of the control in the polysaccharide-treated MCF-7 breast cancer cells. Therefore, the polysaccharides from A. pectinifera merit further investigation with respect to breast cancer chemoprevention.

• Archives of Pharmacal Research
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• 제23권3호
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• pp.243-245
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• 2000

The diethyl ether extract of isodon excisus var. coreanus exhibited significant inhibitory activity in aromatase assay. Bioactivity-guided fractionation of the extract led to the isolation of three active compounds: inflexin(ent-1${\alpha}$-hydroxy-3${\beta}$,6a-diacetoxykau r-16-en-11,15-dione) (1), ursolic acid (2), and ursolic acid 3-O-acetate (3).

• 한국해양바이오학회지
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• 제1권3호
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• pp.193-197
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• 2006

별불가사리 단백추출물을 조제하여 유방암 발생 및 전이억제효과를 측정한 결과 종양세포증식에 관여하는 aromatase 활성이 농도의존적으로 억제효과가 있었으며, 침윤성 유방암에서 과발현하는 COX-2 단백질 발현을 억제하였다. 그리고 유방암이 진행될수록 활성이 증가하는 MMP-9도 농도의존적 저해율을 보였다. 그러므로 별불가사리 단백추출물은 유방암억제기전에 관련된 더 많은 연구를 통하여 유방암 예방물질로서 개발 가능성이 있는 것으로 보인다.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.67-75
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• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

• Archives of Pharmacal Research
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• 제28권12호
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• pp.1365-1375
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• 2005

The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, i.e., $\bigtriangleup^{9}$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated using in vitro bioassays, viz., the human breast cancer cell proliferation assay, the recombinant human estrogen receptor (ER) competitive binding assay, and the reporter gene assay. The inhibitory effects on estrogen were also examined using the ethoxyresorufin-O­deethylase (EROD) assay, the aromatase assay, and the 17$\beta$-estradiol ($E_{2}$) metabolism assay. The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity. This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use. In addition, MSC induced the CYP1A activity and the $E_{2}$ metabolism, but inhibited the aromatase activity, suggesting that the antiestrogenic activity of MSC is also related to the indirect ER-dependent pathway, as a result of the depletion of the in situ $E_{2}$ level available to bind to the ER. In conclusion, pyrogenic products including polycyclic aromatic hydrocarbons (PAHs) in the non-polar fraction, which is the most biologically active fraction among the seven fractions of MSC, might be responsible for the antiestrogenic effect.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.137-137
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• 2003

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.95.2-95
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• 2003

Ketoconazole is a well-studied drug that blocks fungal growth and testosterone synthesis in humans and rodents by inhibiting the activity of cytochrome P-450 enzymes. But there were no reports that ketoconazole affects on enzymes related to degradation of testosterone. Aromatase converts testosterone to estradiol. Change of aromatase protein level may destroy hormone homeostasis. (omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.137-137
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• 2003

Dichlorodiphenyltrichloroethane (DDT) is a widespread environmental pollutant. Earlier reports have demonstrated that DDT is an endocrine-active compound capable of affecting early-stage sexual differentiation in male rats. Experiments based on receptor binding affinity and receptor-mediated transcriptional activation have identified DDE as an androgen receptor antagonist.(omitted)