School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon dong, Jangan-gu, Suwon, Kyeonggi-do, 440-746, South Korea.
Phytother Res. 2013 Dec;27(12):1756-62. doi: 10.1002/ptr.4927. Epub 2013 Jan 21.
Breast cancer is the most common cancer in women worldwide. There are many endocrine adjuvant therapies for breast cancer patients that are categorized according to their mechanisms. Among them, aromatase inhibitors (AIs) that block the synthesis of estrogens have proven superiority compared with tamoxifen and have replaced it as a first-line hormonal therapy. However, AIs also have limitations due to their side effects - increased rate of bone loss and musculoskeletal complaints. We therefore need new candidate AIs with fewer side effects. The extracts of Ginkgo biloba (EGb), which contain phytochemicals from the tree, had biphasic effects for estrogens and osteoporosis-inhibiting activities in our previous experiments. In this study, we explored the possibility of EGb as an AI and their mechanisms. Aromatase activities were inhibited by EGb both in JEG-3 cells and in recombinant CYP19 microsomes. The results of polymerase chain reaction for aromatase from a coding sequence and specific promoter sequences (exon I.a, exon I.c) in JEG-3 cells as well as the results of reporter gene assays showed that EGb dose-dependently decreased the aromatase gene expression. The decreased protein levels were demonstrated by Western blotting. From these results, we concluded that EGb could act as an AI at both the enzyme and transcriptional levels.
乳腺癌是全球女性最常见的癌症。乳腺癌患者有许多内分泌辅助治疗方法,这些方法根据其作用机制进行分类。其中,抑制雌激素合成的芳香酶抑制剂 (AIs) 已被证明优于他莫昔芬,并已取代他莫昔芬成为一线激素治疗药物。然而,由于其副作用,如骨丢失和肌肉骨骼投诉的发生率增加,AIs 也存在局限性。因此,我们需要具有更少副作用的新型候选 AIs。我们之前的实验表明,银杏叶提取物 (EGb) 中的植物化学物质对雌激素具有双相作用和抑制骨质疏松的作用。在这项研究中,我们探讨了 EGb 作为 AI 的可能性及其机制。EGb 抑制 JEG-3 细胞和重组 CYP19 微粒体中的芳香酶活性。JEG-3 细胞中芳香酶从编码序列和特定启动子序列(外显子 I.a、外显子 I.c)的聚合酶链反应结果以及报告基因检测结果表明,EGb 可剂量依赖性降低芳香酶基因表达。Western blot 显示蛋白水平降低。从这些结果中,我们得出结论,EGb 可以在酶和转录水平上作为 AI 发挥作用。