The effects of the standardized extracts of on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells
| Autor: | Mi-Jie Kim, Byeonghak Moon, Seung Min Oh, Kyu Hyuck Chung, Yong Joo Park, Huiyeon Ahn |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Ginkgo biloba extracts
medicine.medical_specialty endocrine system extracts medicine.drug_class Health Toxicology and Mutagenesis medicine.medical_treatment Pharmacology Toxicology 03 medical and health sciences chemistry.chemical_compound 0404 agricultural biotechnology 0302 clinical medicine Internal medicine medicine Adrenocortical carcinoma GE1-350 Aromatase Testosterone Aldosterone Aromatase inhibitor biology Public Health Environmental and Occupational Health 04 agricultural and veterinary sciences medicine.disease H295R cells 040401 food science Environmental sciences Steroid hormone Endocrinology chemistry Steroidogenesis Estrogen 030220 oncology & carcinogenesis biology.protein Hormonal therapy Original Article hormones hormone substitutes and hormone antagonists |
| Zdroj: | Environmental Health and Toxicology, Vol 31 (2016) Environmental Health and Toxicology |
| ISSN: | 2233-6567 |
| Popis: | 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 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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