• 환경생물
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• 제29권1호
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• pp.74-80
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• 2011

In this study we present a mammalian cell culture model that allows to study the effect of endocrine disruptors (EDCs) on aromatase activity of aquatic amphibian, Bombina orientalis. Bombina orientalis aromatase gene was subcloned into a mammalian expression vector and subsequently transfected to mammalian cells. Although the protein expression level of Bombina orientalis aromatase was low, it had a significant aromatase activity. When EDCs were added to aromatase transfected cells, aromatase activity was significantly decreased. We report here that this system may be used to monitor the effect of EDCs on aromatase activity of aquatic organisms.

• Journal of Acupuncture Research
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• 제19권5호
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• pp.136-148
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• 2002

본 연구는 osteoblastic cells에서 estogen 의 생합성을 유도하는 aromatase의 activity에 대한 봉독(蜂毒)작용을 측정하여, 봉독치료시 Arthritis의 진행 억제 및 estogen의 의한 bone formation의 효과여부를 검증하기 위해 실행하였다. 사용된 세포주로는 Osteoblastic phenotype으로 분화가 유도되는 Human leukaemic cell line FLG 29.1 및 the primary first-passage osteoblastic cells (hOB cells)이며, 이들을 각각 배양하고 각각의 RNA를 isolation한 뒤 PCR 증폭을 하였다. Aromatase에 대한 활성인자인 TPA와 TGF-${\beta}1$ 및 봉독을 이용하여 aromatase의 expression 및 activity에 대해 미치는 영향을 측정한 바, aromatase expression은 FLG 29.1 cell와 hoB cells에서, 50nM TPA 24시간 처리, 봉독 2 ~ 4시간 처리와 TGF-${\beta}1$ 3시간 처리로 유도한 결과 TPA와 TGF-${\beta}1$의 경우는 서로 유사하였고, 봉독에서 상대적으로 높게 나타났다. Aromatase activity는 FLG 29.1 cell, hoB cells에서 24시간 incubation한 결과, 모든 실험에서 일정하게 선상증가를 보였다. $5{\mu}{\ell}/m{\ell}$ BV에서 TPA와 TGF-${\beta}1$보다 뚜렷하게 증가하였으며, 0.5mM Bt2-cAMP, 50nM dexametasone처리에서는 유의성이 없었다. Estrogen 생합성을 촉매하는 aromatase activity BV가 처리에서 현저하게 증가하였기에, Rheumatis arthritis의 bone destruction에 대해 BV가 효과적인 역할을 할 것으로 보여진다.

• 생약학회지
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• 제35권2호통권137호
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• pp.147-151
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• 2004

Water extracts from Thesium chinense Tunczaninov (TCTW) and Prunella vulgaris L. (PVW) were tested for aromatase and cyclooxygenase activities. TCTW and PVW were capable of suppressing aromatase in a human placenta microsomal assay. PVW was shown to be more effective than TCTW in the suppression of aromatase activity. TCTW significantly inhibited cyclooxygenase-2 (COX-2) activity at the concentration of 0.25 (p<0.05), 0.5 (p<0.01) and 2.5 mg/ml (p<0.005). PVW also inhibited COX-2 activity in a dose-dependent manner in a concentration range of $0.05{\sim}2.5\;mg/ml$. The expression of COX-2 was inhibitied by TCTW and PVW in western blot analysis. These results suggest that TCTW and PVW may have breast cancer chemopreventive potentials by inhibiting aromatase and cyclooxygenase activities.

• Environmental Analysis Health and Toxicology
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• 제18권2호
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• pp.95-100
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• 2003

본 연구는 환경호르몬(endocrine disruptors)으로 분류되었으며, 제초제로 널리 사용되었던 Dichlorodiphenyltrichloroethane(DDT)가 설치류의 생식세포 중 Leydig 세포의 testosterone(T)생성억제 및 그 관련 작용메카니즘을 규명코자 수행되었다. 먼저 흰쥐의 웅성 생식세포주인 R2C세포에 T의 양 및 aromatase 활성도를 radio immunoassay (RIA)방법을 이용하여 측정하였다. 그 결과 R2C 세포에 황체형성호르몬(LH)를 처리하여 testosterone생성을 증가시킨 후, DDT를 처리한 군들은 대조군에 비하여 농도 의존적으로 T의 양은 감소하였으며, aromatase 활성도는 증가하였다. 또한 DDT자체만 처리한 군에서도 대조군에 비하여 testosterone의 생성이 감소하였다. 이러한 aromatase활성 증가가 estradiol receptor(ER)와의 상호 관련성을 확인하기 위해 ER antagonist인 ICI 182.780를 처리한 후 T의 양 및 aromatase 활성도를 측정한 결과 DDT에 의해 증가된 aromatase활성도가 ICI 182.780에 의해 다시 감소됨을 확인하였다. 또한 DDT에 의해 감소된 T의 양도 ICI 182.780에 의해 다시 회복되었다. In vivo실험으로 흰쥐에 DDT를 직접 투여한 후 정소 내 성 호르몬들을 측정해 본 결과 T의 양은 유의성 있게 감소하였으며, estradiol(E$_2$)의 양은 증가하였으며, aromatase 활성도도 감소하였다. 이러한 결과를 종합해 볼 때 DDT는 aromatase를 감소시키고, 이렇게 감소된 aromatase에 의해 testosterone 생성량을 억제하고, 이러한 DDT의 aromatase의 감소는 ER을 경유하는 것으로 추정할 수 있다.

• 생명과학회지
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• 제18권4호
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• pp.503-508
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• 2008

동해 해양심층수의 유방암예방 효능과 전이에 미치는 영향을 알아보기 위해 cytochrome P450 1A1 활성과 aromatase 활성 및 유방암세포의 침윤성, 이와 관련된 MMP-9 의 활성과 그 단백질 발현에 미치는 영향을 조사하였다. 해양심층수는 체내외의 여러 화학물질을 체내에서 활성화시켜 발암이나 돌연변이 등을 유발시키는 것으로 알려진 cytochrome P450 1A1을 경도의존적으로 저해시켰다. 또한 호르몬 의존성 유방암의 진행에 관여하는 aromatase의 활성도 경도의존적으로 저해시켰다($5.6{\sim}51.9%$). 해양심층수 처리에 의해 사람유방암세포인 MDA-MB-231 세포의 침윤성은 $73.7{\sim}29.4%$로 감소하였으며, 세포의 침윤시 작용하는 단백질 분해 효소인 MMP-9의 활성과 단백질 발현도 경도의존적으로 억제되었다. 따라서 해양심층수는 유방암 예방과 전이관련의 더 많은 연구에 의해 유방암 예방과 전이 억제작용을 증명할 수 있을 것으로 보인다.

• 환경생물
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• 제21권3호
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• pp.308-312
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• 2003

Various pesticides known or suspected to interfere with steroid hormone function were screened toy effects in leydig cells on catalytic activity and mRNA expression of aromatase. Dichlorodiphenyltrichloroethane (DDT) is a widespread environmental pollutant. In this study, we investigated the effect of DDT on testosterone production through aromatase activity and its molecular mechanism in testicular leydig cell, R2C by using radioimmunoassay (RIA). As the results, the potent leydig: cell activator LH increased testosterone production compared to the control. DDT exposure significantly decreased testosterone production in R2C cell. In addition, DDT was found to increase aromatase gene expression and activity in R2C cell in a dose dependent manner. In order to assess whether the suppressive effects of DDT on LH-inducible testosterone (T) production might be influenced by the ER, ICI 182.780 was used, and it was found that these inhibitory effects of DDT were antagonized by ICI 182.780, implying that the estrogen receptor (ER) mediates the suppressive effects of DDT. Furthermore, the inducible effects of DDT on aromatase gene expression might be influenced by the ER, ICI 182.780 was used, and it was found that these enhancing effects of DDT were antagonized by ICI 182.780, implying that the ER mediates the inducible effects of DDT. Our results indicated that DDT inhibition of luteinizing hormone (LH) -inducible T production in R2C cell is mediated through aromatase. However, the precise mechanisms by which DDT enhance in R2C cell remains unknown. The current study suggests the possibility that DDT might act as a modulator aromatase gene transcription.

• Archives of Pharmacal Research
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• 제22권3호
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• pp.309-312
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• 1999

In searching for potent cancer chemopreventive agents from synthetic or natural products, 28 randomly selected flavonoids were screened for inhibitory effects against partially purified aromatase prepared form human placenta. Over 50% of the flavonoids significantly inhibited aromatase activity, with greatest activity being demonstrated with apigenin $(IC_{50}: 0.9{\mu}/mL)$, chrysin $(IC_{50}: 1.1{\mu}/mL)$ , and hesperetin $(IC_{50}:1.0{\mu}/mL)$.

• 동의생리병리학회지
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• 제20권1호
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• pp.88-92
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• 2006

Genistein was tested for chemopreventive potential against breast cancer by measuring the effect on proliferation of human breast cancer cells, human placental aromatase activity and cyclooxygenases-2 (COX-2) expression and activity, Genistein inhibited the growth of estrogen-independent MDA-MB-231 human breast cancer cell. However, there is no inhibitory effect of genistein on human placental aromatase activity. The expression of COX-2 was inhibited by genistein in Western blot analysis. Genistein significantly inhibited COX-2 activity at the concentrations of 10 (p<0.05), 25 (p<0.05) and 50 ${\mu}M$ (p<0.01). These results suggest that genistein may have breast cancer chemopreventive potential by inhibiting the growth of human breast cancer cell and expression and activity of COX-2.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6317-6325
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• 2015

Ginkgo biloba extract (GBE) is a popular phytomedicine and has been used for disorders of the central nervous system, cardiovascular, renal, respiratory, and circulatory diseases. Although GBE is a complex mixture of over 300 compounds, its major components are 24% flavonoids and 6% terpene lactones. In this study, we tested the inhibitory effects of the three major flavonoids (kaempferol, quercetin, and isorhamnetin) from GBE, independently and as mixtures, on aromatase activity using JEG-3 cells (human placental cells) and recombinant proteins (human placental microsome). In both systems, kaempferol showed the strongest inhibitory effects among the three flavonoids; the flavanoid mixtures exerted increased inhibitory effects. The results of exon I.1-driven luciferase reporter gene assays supported the increased inhibitory effects of flavonoid mixtures, accompanied by suppression of estrogen biosynthesis. In the RT-PCR analysis, decreased patterns of aromatase promoter I.1 mRNA expressions were observed, which were similar to the aromatase inhibition patterns of flavonoids and their mixtures. The present study demonstrated that three flavonoids synergistically inhibit estrogen biosynthesis through aromatase inhibition, decrease CYP19 mRNA, and induce transcriptional suppression. Our results support the usefulness of flavonoids in adjuvant therapy for breast cancer by reducing estrogen levels with reduced adverse effects due to estrogen depletion.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.70-71
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• 2003

Dichlorodiphenyltrichloroethane (DDT), is a widespread environmental pollutant. In this study, we investigated the effect of DDT on testosterone production through aromatase and investigated its molecular mechanism in testicular leydig cell, R2C. We investigated that the effects of DDT on testosterone production and its effects on aromatase activity in R2C cell by radio immunoassay (RIA). (omitted)