Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells.
Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells.
复制标题
DOI：
10.1093/carcin/22.3.409
复制
发表时间：
2001-03
期刊：
影响因子：
4.7
通讯作者：
Nianzeng Xing;Yi Chen;Susan H. Mitchell;Charles Y. F. Young
中科院分区：
文献类型：
--
作者：
Nianzeng Xing;Yi Chen;Susan H. Mitchell;Charles Y. F. Young
雄激素受体（AR）参与前列腺癌的发生和进展。为了找到可能提供减弱 AR 功能的新机制的新化合物，我们研究了天然类黄酮化学物质槲皮素对雄激素反应性 LNCaP 前列腺癌细胞系中雄激素作用的影响。 Western blot分析表明，槲皮素以剂量依赖性方式抑制AR蛋白的表达。为了证明对 AR 表达的抑制作用实际上可以降低其功能，我们发现槲皮素抑制前列腺特异性、雄激素调节的肿瘤标志物 PSA 和 hK2 的分泌。槲皮素下调了 PSA、NKX3.1 和鸟氨酸脱羧酶 (ODC) 等雄激素调节基因的 mRNA 水平。瞬时转染进一步表明槲皮素在转录水平抑制AR介导的PSA表达。最后证明槲皮素可以在转录水平上抑制AR基因的表达。我们的结果表明，槲皮素可以通过抑制 AR 的表达来减弱 AR 的功能，并有可能成为前列腺癌的化学预防和/或化疗剂。
The androgen receptor (AR) is involved in the development and progression of prostate cancer. In order to find new compounds that may present novel mechanisms to attenuate the function of AR, we investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific, androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase (ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level. Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level. Our result suggests that quercetin can attenuate the function of AR by repressing its expression and has the potential to become a chemopreventive and/or chemotherapeutic agent for prostate cancer.