Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation:: Identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer
Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation:: Identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer
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DOI：
10.1158/0008-5472.can-05-1865
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发表时间：
2006-01-01
期刊：
影响因子：
11.2
通讯作者：
Lu, JX
中科院分区：
文献类型：
--
作者：
Jiang, C;Lee, HJ;Lu, JX
雄激素和雄激素受体（AR）介导的信号传导对前列腺癌的发展至关重要。发现针对雄激素和AR信号的新型天然植物化学物质，东方草药对这种疾病的化学预防具有令人兴奋的前景。在这篇文章中，我们报道了在雄激素依赖性LNCaP人类前列腺癌细胞模型中，含有韩国当归（AGN）根和其他九种东方草药的草药配方（称为KMKKT）的乙醇提取物的强大和持久的抗雄激素和AR活性的发现。评估的功能性生物标志物包括抑制前列腺特异性抗原（PSA） mRNA和蛋白的表达（IC50，类似于7 μ g/mL， 48小时暴露），通过g抑制雄激素诱导的细胞增殖，抑制雄激素在不引起细胞凋亡的暴露浓度下抑制神经内分泌分化的能力。通过活性引导分离，我们从AGN中鉴定出一种新的抗雄激素和AR化合物，其IC50近似于0.4 μ g/mL （1.3 μ mol/L， 48小时暴露），可抑制PSA表达。Decursin还概述了AGN和KMKKT提取物的神经内分泌分化诱导和G，阻滞作用。从机制上讲，纯形式的前驱素或作为AGN或KMKKT提取物的成分抑制雄激素刺激的AR向细胞核的易位，并下调AR蛋白丰度，而不影响AR mRNA水平。德柏素和含德柏素的草药提取物具有新的抗雄激素和AR活性，对前列腺癌和其他雄激素依赖性疾病的化学预防和治疗具有重要意义。
Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling front Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, similar to 7 mu g/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G, arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of similar to 0.4 mu g/mL (1.3 mu mol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G, arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases.