Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus)
Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus)
复制标题
DOI：
10.1158/0008-5472.can-06-2206
复制
发表时间：
2006-12-15
期刊：
影响因子：
11.2
通讯作者：
Williams, Dudley
中科院分区：
文献类型：
--
作者：
Chen, Shiuan;Oh, Sei-Ryang;Williams, Dudley
白色蘑菇（双孢蘑菇）是一种潜在的乳腺癌化学预防剂，因为它们抑制芳香酶活性和雌激素生物合成。因此，我们评估了蘑菇提取物在雌激素受体阳性/芳香化酶阳性MCF-7aro细胞系中的体外和体内活性。蘑菇提取物降低睾酮诱导的MCF-7aro细胞的细胞增殖，但对MCF-10A，一种非致瘤细胞系没有影响。大多数有效的蘑菇化学物质可溶于乙酸乙酯。在乙酸乙酯馏分中发现的主要活性化合物是不饱和脂肪酸，如亚油酸、亚麻酸和共轭亚油酸。亚油酸和共轭亚油酸与中国仓鼠卵巢细胞中表达的芳香化酶突变体的相互作用表明，这些脂肪酸抑制芳香化酶具有相似的效力，并且活性位点区域的突变影响其与这两种脂肪酸的相互作用。而这些结果表明，这两种化合物结合的芳香化酶的活性位点，抑制动力学分析表明，它们是非竞争性抑制剂雄烯二酮。由于仅发现共轭亚油酸抑制MCF-7aro细胞的睾酮依赖性增殖，因此蘑菇中生理学相关的芳香酶抑制剂最有可能是共轭亚油酸及其衍生物。使用注射MCF-7aro细胞的裸鼠显示蘑菇化学品的体内作用。研究表明，蘑菇提取物降低肿瘤细胞增殖和肿瘤重量，而对凋亡率没有影响。因此，我们的研究说明了蘑菇提取物及其主要脂肪酸成分的体外和体内抗癌活性。
White button mushrooms (Agaricus bisporous) are a potential breast cancer chemopreventive agent, as they suppress aromatase activity and estrogen biosynthesis. Therefore, we evaluated the activity of mushroom extracts in the estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in vivo. Mushroom extract decreased testosterone-induced cell proliferation in MCF-7aro cells but had no effect on MCF-10A, a nontumorigenic cell line. Most potent mushroom chemicals are soluble in ethyl acetate. The major active compounds found in the ethyl acetate fraction are unsaturated fatty acids such as linoleic acid, linolenic acid, and conjugated linoleic acid. The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants expressed in Chinese hamster ovary cells showed that these fatty acids inhibit aromatase with similar potency and that mutations at the active site regions affect its interaction with these two fatty acids. Whereas these results suggest that these two compounds bind to the active site of aromatase, the inhibition kinetic analysis indicates that they are noncompetitive inhibitors with respect to androstenedione. Because only conjugated linoleic acid was found to inhibit the testosterone-dependent proliferation of MCF-7aro cells, the physiologically relevant aromatase inhibitors in mushrooms are most likely conjugated linoleic acid and its derivatives. The in vivo action of mushroom chemicals was shown using nude mice injected with MCF-7aro cells. The studies showed that mushroom extract decreased both tumor cell proliferation and tumor weight with no effect on rate of apoptosis. Therefore, our studies illustrate the anticancer activity in vitro and in vivo of mushroom extract and its major fatty acid constituents.