Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450
Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/2/203 |
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| author | Katyayani Sharma Angelo Lanzilotto Jibira Yakubu Søren Therkelsen Clarissa Daniela Vöegel Therina Du Toit Flemming Steen Jørgensen Amit V. Pandey |
| author_facet | Katyayani Sharma Angelo Lanzilotto Jibira Yakubu Søren Therkelsen Clarissa Daniela Vöegel Therina Du Toit Flemming Steen Jørgensen Amit V. Pandey |
| author_sort | Katyayani Sharma |
| collection | DOAJ |
| description | Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential oils or their metabolites, like lavender oil and tea tree oil, have been reported to act as potential EDCs and contribute towards sex steroid imbalance in cases of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of essential oils with CYP17A1 and CYP19A1. Functional assays were performed using the radiolabeled substrates or Liquid Chromatography–High-Resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone, and (−)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these essential oils in various beauty and hygiene products is common, but only limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output and ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for novel compounds against hyperandrogenic disorders such as PCa and PCOS. |
| first_indexed | 2024-03-07T22:40:57Z |
| format | Article |
| id | doaj.art-b28db5315d1941499863869ea0b05810 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-07T22:40:57Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b28db5315d1941499863869ea0b058102024-02-23T15:09:21ZengMDPI AGBiomolecules2218-273X2024-02-0114220310.3390/biom14020203Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450Katyayani Sharma0Angelo Lanzilotto1Jibira Yakubu2Søren Therkelsen3Clarissa Daniela Vöegel4Therina Du Toit5Flemming Steen Jørgensen6Amit V. Pandey7Division of Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children’s Hospital, Inselspital, University of Bern, 3010 Bern, SwitzerlandDivision of Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children’s Hospital, Inselspital, University of Bern, 3010 Bern, SwitzerlandDivision of Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children’s Hospital, Inselspital, University of Bern, 3010 Bern, SwitzerlandDivision of Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children’s Hospital, Inselspital, University of Bern, 3010 Bern, SwitzerlandTranslational Hormone Research Program, Department of Biomedical Research, University of Bern, 3010 Bern, SwitzerlandDivision of Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children’s Hospital, Inselspital, University of Bern, 3010 Bern, SwitzerlandDepartment of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, DenmarkDivision of Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children’s Hospital, Inselspital, University of Bern, 3010 Bern, SwitzerlandEndocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential oils or their metabolites, like lavender oil and tea tree oil, have been reported to act as potential EDCs and contribute towards sex steroid imbalance in cases of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of essential oils with CYP17A1 and CYP19A1. Functional assays were performed using the radiolabeled substrates or Liquid Chromatography–High-Resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone, and (−)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these essential oils in various beauty and hygiene products is common, but only limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output and ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for novel compounds against hyperandrogenic disorders such as PCa and PCOS.https://www.mdpi.com/2218-273X/14/2/203EDCsprostate cancerCYP17A1steroidogenesisDHEAanti-cancer drugs |
| spellingShingle | Katyayani Sharma Angelo Lanzilotto Jibira Yakubu Søren Therkelsen Clarissa Daniela Vöegel Therina Du Toit Flemming Steen Jørgensen Amit V. Pandey Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450 Biomolecules EDCs prostate cancer CYP17A1 steroidogenesis DHEA anti-cancer drugs |
| title | Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450 |
| title_full | Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450 |
| title_fullStr | Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450 |
| title_full_unstemmed | Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450 |
| title_short | Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450 |
| title_sort | effect of essential oil components on the activity of steroidogenic cytochrome p450 |
| topic | EDCs prostate cancer CYP17A1 steroidogenesis DHEA anti-cancer drugs |
| url | https://www.mdpi.com/2218-273X/14/2/203 |
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