PDF(Pubmed)
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 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.
摘要：
内分泌干扰化学物质（EDC）可能通过改变类固醇代谢来影响前列腺癌（PCa）的发展。尽管它们控制肿瘤生长的确切作用机制尚不清楚，EDC可抑制类固醇生成酶,如CYP17A1或CYP19A1,其参与雄激素或雌激素的产生。高水平的循环雄激素与男性的PCa和女性的多囊卵巢综合征（PCOS）有关。精油或其代谢物，像薰衣草油和茶树油，据报道，由于暴露于薰衣草类香料，男孩青春期前男性乳房发育症和女孩早产性类固醇失衡。我们筛选了一系列EO成分以确定它们对CYP17A1和CYP19A1的影响。进行计算对接以预测精油与CYP17A1和CYP19A1的结合。使用放射性标记的底物或液相色谱-高分辨率质谱进行功能测定,并在LNCaP细胞中进行细胞活力测定。许多测试化合物结合接近CYP17A1的活性位点,并且(+)-Cedrol具有与CYP17A1和CYP19A1的最佳结合。桉树脑,二氢-β-离子酮,和（-）-α-pine烯显示20％至40％的脱氢表雄酮产生抑制；一些化合物也影响CYP19A1。在各种美容和卫生用品中广泛使用这些精油是常见的，但对其潜在有害副作用的了解有限。我们的结果表明，长时间接触这些精油可能会导致类固醇失衡。另一方面,由于它们对降低雄激素输出和在类固醇细胞色素P450的活性位点结合的能力的作用，这些化合物可能为抗PCa和PCOS等高雄激素性疾病的新型化合物提供设计思路。
