The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells
Identifieur interne : 000A18 ( Main/Merge ); précédent : 000A17; suivant : 000A19The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells
Auteurs : Mijie Kim [Corée du Sud] ; Yong Joo Park [Corée du Sud] ; Huiyeon Ahn [Corée du Sud] ; Byeonghak Moon [Corée du Sud] ; Kyu Hyuck Chung [Corée du Sud] ; Seung Min Oh [Corée du Sud]Source :
- Environmental Health and Toxicology [ 2233-6567 ] ; 2016.
Abstract
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
Cortisol, aldosterone, testosterone, and 17β-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 (3β-HSD2 and 17β-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis.
H295R cells exposed to EGb761 (10 and 100 μg/mL) showed a significant decrease in 17β-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17β-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.
These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17β-HSD1, and lead to a decrease in 17β-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.
Url:
DOI: 10.5620/eht.e2016010
PubMed: 27188280
PubMed Central: 4886827
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The effects of the standardized extracts of <italic>Ginkgo biloba</italic> on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells</title><author><name sortKey="Kim, Mijie" sort="Kim, Mijie" uniqKey="Kim M" first="Mijie" last="Kim">Mijie Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-eht-31-e2016010">Oncology and Antimicrobial Products Division, National Institute of Food and Drug Safety Evaluation, Cheongju,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Yong Joo" sort="Park, Yong Joo" uniqKey="Park Y" first="Yong Joo" last="Park">Yong Joo Park</name><affiliation wicri:level="1"><nlm:aff id="af2-eht-31-e2016010">School of Pharmacy, Sungkyunkwan University, Suwon,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ahn, Huiyeon" sort="Ahn, Huiyeon" uniqKey="Ahn H" first="Huiyeon" last="Ahn">Huiyeon Ahn</name><affiliation wicri:level="1"><nlm:aff id="af3-eht-31-e2016010">Department of Nanofusion Technology, Hoseo University, Asan,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moon, Byeonghak" sort="Moon, Byeonghak" uniqKey="Moon B" first="Byeonghak" last="Moon">Byeonghak Moon</name><affiliation wicri:level="1"><nlm:aff id="af3-eht-31-e2016010">Department of Nanofusion Technology, Hoseo University, Asan,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chung, Kyu Hyuck" sort="Chung, Kyu Hyuck" uniqKey="Chung K" first="Kyu Hyuck" last="Chung">Kyu Hyuck Chung</name><affiliation wicri:level="1"><nlm:aff id="af2-eht-31-e2016010">School of Pharmacy, Sungkyunkwan University, Suwon,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Oh, Seung Min" sort="Oh, Seung Min" uniqKey="Oh S" first="Seung Min" last="Oh">Seung Min Oh</name><affiliation wicri:level="1"><nlm:aff id="af3-eht-31-e2016010">Department of Nanofusion Technology, Hoseo University, Asan,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27188280</idno><idno type="pmc">4886827</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886827</idno><idno type="RBID">PMC:4886827</idno><idno type="doi">10.5620/eht.e2016010</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000738</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000738</idno><idno type="wicri:Area/Pmc/Curation">000738</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000738</idno><idno type="wicri:Area/Pmc/Checkpoint">000529</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000529</idno><idno type="wicri:Area/Ncbi/Merge">008301</idno><idno type="wicri:Area/Ncbi/Curation">008301</idno><idno type="wicri:Area/Ncbi/Checkpoint">008301</idno><idno type="wicri:Area/Main/Merge">000A18</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The effects of the standardized extracts of <italic>Ginkgo biloba</italic> on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells</title><author><name sortKey="Kim, Mijie" sort="Kim, Mijie" uniqKey="Kim M" first="Mijie" last="Kim">Mijie Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-eht-31-e2016010">Oncology and Antimicrobial Products Division, National Institute of Food and Drug Safety Evaluation, Cheongju,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Park, Yong Joo" sort="Park, Yong Joo" uniqKey="Park Y" first="Yong Joo" last="Park">Yong Joo Park</name><affiliation wicri:level="1"><nlm:aff id="af2-eht-31-e2016010">School of Pharmacy, Sungkyunkwan University, Suwon,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ahn, Huiyeon" sort="Ahn, Huiyeon" uniqKey="Ahn H" first="Huiyeon" last="Ahn">Huiyeon Ahn</name><affiliation wicri:level="1"><nlm:aff id="af3-eht-31-e2016010">Department of Nanofusion Technology, Hoseo University, Asan,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moon, Byeonghak" sort="Moon, Byeonghak" uniqKey="Moon B" first="Byeonghak" last="Moon">Byeonghak Moon</name><affiliation wicri:level="1"><nlm:aff id="af3-eht-31-e2016010">Department of Nanofusion Technology, Hoseo University, Asan,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chung, Kyu Hyuck" sort="Chung, Kyu Hyuck" uniqKey="Chung K" first="Kyu Hyuck" last="Chung">Kyu Hyuck Chung</name><affiliation wicri:level="1"><nlm:aff id="af2-eht-31-e2016010">School of Pharmacy, Sungkyunkwan University, Suwon,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Oh, Seung Min" sort="Oh, Seung Min" uniqKey="Oh S" first="Seung Min" last="Oh">Seung Min Oh</name><affiliation wicri:level="1"><nlm:aff id="af3-eht-31-e2016010">Department of Nanofusion Technology, Hoseo University, Asan,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Environmental Health and Toxicology</title><idno type="eISSN">2233-6567</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>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 <italic>Ginkgo biloba</italic> (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 <italic>in vitro</italic> model to predict effects on human adrenal steroidogenesis. </p></sec><sec><title>Methods</title><p>Cortisol, aldosterone, testosterone, and 17β-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 (3β-HSD2 and 17β-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. </p></sec><sec><title>Results</title><p>H295R cells exposed to EGb761 (10 and 100 μg/mL) showed a significant decrease in 17β-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17β-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. </p></sec><sec><title>Conclusions</title><p>These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17β-HSD1, and lead to a decrease in 17β-estradiol and testosterone. 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sortKey="Watanabe, G" uniqKey="Watanabe G">G Watanabe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Von Krogh, K" uniqKey="Von Krogh K">K von Krogh</name></author><author><name sortKey="Harjen, H" uniqKey="Harjen H">H Harjen</name></author><author><name sortKey="Alm S, C" uniqKey="Alm S C">C Almås</name></author><author><name sortKey="Zimmer, Ke" uniqKey="Zimmer K">KE Zimmer</name></author><author><name sortKey="Dahl, E" uniqKey="Dahl E">E Dahl</name></author><author><name sortKey="Olsaker, I" uniqKey="Olsaker I">I Olsaker</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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