Environmental Analysis Health and Toxicology

  • Volume 31
  • /
  • Pages.10.1-10.8
  • /
  • 2016
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  • 2671-9525(eISSN)
The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells

  • Kim, Mijie (Oncology and Antimicrobial Products Division, National Institute of Food and Drug Safety Evaluation) ;
  • Park, Yong Joo (School of Pharmacy, Sungkyunkwan University) ;
  • Ahn, Huiyeon (Department of Nanofusion Technology, Hoseo University) ;
  • Moon, Byeonghak (Department of Nanofusion Technology, Hoseo University) ;
  • Chung, Kyu Hyuck (School of Pharmacy, Sungkyunkwan University) ;
  • Oh, Seung Min (Department of Nanofusion Technology, Hoseo University)
  • Received : 2016.03.17
  • Accepted : 2016.04.14
  • Published : 2016.01.01
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Abstract

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.

Keywords

References

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