Nobiletin suppresses cell viability through AKT pathways in PC-3 and DU-145 prostate cancer cells.
Nobiletin suppresses cell viability through AKT pathways in PC-3 and DU-145 prostate cancer cells.
复制标题
DOI：
10.1186/2050-6511-15-59
复制
发表时间：
2014-10-24
影响因子：
2.9
通讯作者：
Chen YC
中科院分区：
文献类型：
--
作者：
Chen J;Creed A;Chen AY;Huang H;Li Z;Rankin GO;Ye X;Xu G;Chen YC
诺比列汀是一种无毒的膳食类黄酮，具有抗癌特性。据报道，诺比列汀可降低前列腺癌的风险，但其作用机制尚未完全明确。在本研究中，我们研究了诺比列汀对前列腺癌细胞系PC - 3和DU - 145的影响。
通过高效液相色谱法（HPLC）从一种多甲氧基黄酮混合物中分离出诺比列汀，采用基于MTS的检测方法分析细胞活力。通过酶联免疫吸附测定（ELISA）和蛋白质印迹法检测蛋白质表达。通过荧光素酶检测法检测基因表达。通过质粒转染操作基因组分来检测相关通路。
数据显示，诺比列汀降低了两种前列腺癌细胞系的细胞活力，在PC - 3细胞中的活力降低更为显著。在两种细胞系中，缺氧诱导因子 - 1α（HIF - 1α）的表达和蛋白激酶B（AKT）的磷酸化均降低。血管内皮生长因子（VEGF）的表达在PC - 3细胞中受到抑制，但在DU - 145细胞中未受抑制。在DU - 145细胞中，c - Myc表达降低。诺比列汀下调DU145细胞核中核因子 - κB（p50）的表达，但不影响整个细胞。它还抑制PC - 3细胞的整个细胞和细胞核中核因子 - κB的表达。提高HIF - 1α水平可逆转诺比列汀对VEGF表达的抑制作用，上调AKT水平可逆转其对HIF - 1α表达的抑制作用。我们推测，在两种前列腺细胞中，AKT可能通过其对核因子 - κB的作用影响细胞活力。诺比列汀对PC - 3细胞系中VEGF表达的影响是通过AKT / HIF - 1α通路实现的。
综上所述，我们的研究结果表明，诺比列汀通过AKT通路抑制细胞活力，对更具转移性的PC - 3细胞系具有更显著的作用。由于对更恶性的细胞类型有这种增强的作用，诺比列汀可用于提高前列腺癌的生存率。
Nobiletin is a non-toxic dietary flavonoid that possesses anti-cancer properties. Nobiletin has been reported to reduce the risk of prostate cancer, but the mechanism is not well understood. In this study, we investigated the effects of nobiletin in prostate cancer cell lines PC-3 and DU-145. Nobiletin was isolated from a polymethoxy flavonoid mixture using HPLC, cell viability was analyzed with MTS-based assays. Protein expression was examined by ELISA and western blotting. Gene expression was examined by luciferase assay. And the pathways were examined by manipulating genetic components with plasmid transfection. Data showed that nobiletin decreased cell viability in both prostate cell lines, with a greater reduction in viability in PC-3 cells. HIF-1α expression and AKT phosphorylation were decreased in both cell lines. The VEGF expression was inhibited in PC-3 but not DU-145 cells. cMyc expression was decreased in DU-145 cells. Nobiletin down-regulated NF-κB (p50) expression in nuclei of DU145 cells but not whole cells. It also suppressed NF-κB expression in both whole cells and nuclei of PC-3 cells. Increasing HIF-1α levels reversed nobiletin’s inhibitory effects on VEGF expression, and up-regulating AKT levels reversed its inhibitory effects on HIF-1α expression. We speculate that AKT influences cell viability probably by its effect on NF-κB in both prostate cells. The effect of nobiletin on VEGF expression in PC-3 cell lines was through the AKT/HIF-1α pathway. Taken together, our results show that nobiletin suppresses cell viability through AKT pathways, with a more profound effect against the more metastatic PC-3 line. Due to this enhanced action against a more malignant cell type, nobiletin may be used to improve prostate cancer survival rates.
登录
查看更多内容
影响因子：
168.9
作者：
Grönberg, H
通讯作者：
Grönberg, H
影响因子：
2.1
作者：
Crawford, E. David
通讯作者：
Crawford, E. David
影响因子：
4.3
作者：
Shelke, Abhay R.;Mohile, Supriya G.
通讯作者：
Mohile, Supriya G.
影响因子：
11.2
作者：
Kim, SJ;Uehara, H;Fidler, IJ
通讯作者：
Fidler, IJ
影响因子：
4.2
作者：
McCann, SE;Freudenheim, JL;Graham, S
通讯作者：
Graham, S