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bioRxiv · 10.1101/2023.10.31.564977

Essential oil terpenes may inhibit steroidogenic cytochrome P450 activities.

Sharma, K.·Lanzilotto, A.·Yakubu, J.·Therkelsen, S.·Vöegel, C. D.·du Toit, T.·Jorgensen, F. S.·Pandey, A. V.
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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 Cytochrome P450 c17 (CYP17A1) or aromatase (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 (EOs) 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 regular exposure to lavender-based fragrances among Hispanic population. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1 Computational docking was performed to predict the binding of EOs 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-{beta}-Ionone & (-)--pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these EOs 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.

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Sharma, K., Lanzilotto, A., Yakubu, J., Therkelsen, S., Vöegel, C. D., du Toit, T., Jorgensen, F. S., Pandey, A. V.. 2023-11-02. Essential oil terpenes may inhibit steroidogenic cytochrome P450 activities.. https://doi.org/10.1101/2023.10.31.564977

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