Version 1
: Received: 31 October 2023 / Approved: 1 November 2023 / Online: 1 November 2023 (10:12:15 CET)
Version 2
: Received: 26 January 2024 / Approved: 28 January 2024 / Online: 29 January 2024 (09:10:10 CET)
Sharma, K.; Lanzilotto, A.; Yakubu, J.; Therkelsen, S.; Vöegel, C.D.; Du Toit, T.; Jørgensen, F.S.; Pandey, A.V. Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450. Biomolecules2024, 14, 203.
Sharma, K.; Lanzilotto, A.; Yakubu, J.; Therkelsen, S.; Vöegel, C.D.; Du Toit, T.; Jørgensen, F.S.; Pandey, A.V. Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450. Biomolecules 2024, 14, 203.
Sharma, K.; Lanzilotto, A.; Yakubu, J.; Therkelsen, S.; Vöegel, C.D.; Du Toit, T.; Jørgensen, F.S.; Pandey, A.V. Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450. Biomolecules2024, 14, 203.
Sharma, K.; Lanzilotto, A.; Yakubu, J.; Therkelsen, S.; Vöegel, C.D.; Du Toit, T.; Jørgensen, F.S.; Pandey, A.V. Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450. Biomolecules 2024, 14, 203.
Abstract
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 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 case 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, and functional assays were done 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 & (-)-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 a 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, ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for the novel compounds against hyperandrogenic disorders such as PCa and PCOS.
Keywords
EDCs; Prostate cancer; CYP17A1; steroidogenesis; DHEA; anti cancer drugs
Subject
Medicine and Pharmacology, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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