Szaefer Hanna, Licznerska Barbara, Sobierajska Hanna, Baer-Dubowska Wanda
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, 60-806 Poznań, Poland.
Molecules. 2025 Jul 23;30(15):3079. doi: 10.3390/molecules30153079.
Estrogens are considered the most important risk factor for the development of breast cancer. Therefore, attempts are being made to reduce their level through diminished synthesis on one hand and to protect against the formation of DNA-damaging estrogen metabolites on the other. Cytochromes P450 (CYPs) play key roles in estrogen synthesis and catabolism, leading to potentially carcinogenic metabolites. CYP19 (aromatase) catalyzes the conversion of androgens to estrogens. The estrogen receptor-dependent pathway induces cell growth. CYP1 family enzymes, particularly CYP1B1, are involved in the redox cycling of estrogen metabolites and the subsequent estrogen-DNA adducts formation. Naturally occurring phytochemicals of different classes were shown to modulate the CYP expression and activity in cell-free systems or breast cancer cells. One of the most promising CYP19 inhibitors is chrysin (flavone), while stilbenes seem to be the most effective CYP1B1 inhibitors. In most cases, their effect is not specific. Therefore, different approaches are made to find the best candidate for the drug prototype of a new therapeutic or chemopreventive agent and to improve its pharmacokinetic parameters. This review presents and discusses the possible effects on major CYPs involved in estrogen metabolism by phytochemicals from the most investigated classes, namely flavonoids, stilbenes, and glucosinolates breakdown products.
雌激素被认为是乳腺癌发生的最重要风险因素。因此，一方面人们试图通过减少合成来降低其水平，另一方面试图防止形成具有DNA损伤作用的雌激素代谢产物。细胞色素P450（CYPs）在雌激素合成和分解代谢中起关键作用，会产生潜在的致癌代谢产物。CYP19（芳香化酶）催化雄激素向雌激素的转化。雌激素受体依赖性途径可诱导细胞生长。CYP1家族酶，尤其是CYP1B1，参与雌激素代谢产物的氧化还原循环以及随后雌激素-DNA加合物的形成。不同种类的天然植物化学物质已被证明可在无细胞系统或乳腺癌细胞中调节CYP的表达和活性。最有前景的CYP19抑制剂之一是白杨素（黄酮），而芪类似乎是最有效的CYP1B1抑制剂。在大多数情况下，它们的作用并不具有特异性。因此，人们采用了不同的方法来寻找新型治疗或化学预防药物原型的最佳候选物，并改善其药代动力学参数。本综述介绍并讨论了来自研究最多的几类植物化学物质，即黄酮类、芪类和硫代葡萄糖苷分解产物，对参与雌激素代谢的主要CYPs可能产生的影响。
