Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression
Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression
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DOI：
10.1007/s00432-005-0005-4
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发表时间：
2005-11-01
影响因子：
3.6
通讯作者：
Arunakaran, J
中科院分区：
文献类型：
--
作者：
Vijayababu, MR;Kanagaraj, P;Arunakaran, J
前列腺癌是主要的健康问题，也是男性癌症死亡的主要原因。槲皮素是一种新型抗肿瘤和抗氧化剂，其参与雄激素非依赖性前列腺癌细胞细胞周期停滞的分子机制仍不清楚。在这项研究中，我们通过调节前列腺癌细胞 (PC-3) 中的 Cdc2/Cdk-1 蛋白，研究了槲皮素对增殖和细胞周期停滞的影响。 PC-3细胞是人雄激素非依赖性癌细胞并且与浓度为50和100μM的槲皮素一起培养24小时。分析细胞增殖、凋亡和细胞周期分布。通过蛋白质印迹分析研究了 Cdc2/Cdk-1、cyclin B1、cyclin A、p21/Cip1、pRb、pRb2/p130、Bcl-2、Bcl-X-L、Bax 和 caspase-3 蛋白的表达。添加槲皮素导致 Cdc2/Cdk-1、细胞周期蛋白 B1 和磷酸化 pRb 的表达显着降低，而 p21 的表达增加。流式细胞术分析表明，槲皮素可阻断 G2-M 期转变，并显着诱导细胞凋亡。 Bcl-2 和 Bcl-X-L 等凋亡标志物显着减少，Bax 和 caspase-3 增加。从这项研究中得出的结论是，槲皮素通过改变细胞周期调节因子和凋亡蛋白的表达来抑制前列腺癌细胞增殖。
Prostate cancer is the major health problem and the leading cause of male cancer death. Quercetin is a novel antitumor and antioxidant, whose molecular mechanism involved in cell cycle arrest in androgen independent prostate cancer cells remains unclear. In this study, we investigated the effects of quercetin on proliferation and cell cycle arrest by modulation of Cdc2/Cdk-1 protein in prostate cancer cells (PC-3). PC- 3 cells are human androgen independent cancer cells and were cultured with quercetin at concentrations of 50 and 100 mu M for 24 h. Cell proliferation, apoptosis and cell cycle distribution were analyzed. Expression of Cdc2/Cdk-1, cyclin B1, cyclin A, p21/Cip1, pRb, pRb2/p130, Bcl-2, Bcl-X-L, Bax and caspase-3 proteins were studied with western blot analysis. Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorlyated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X-L were significantly decreased and Bax and caspase-3 were increased. From this study, it was concluded that quercetin inhibits prostate cancer cell proliferation by altering the expression of cell cycle regulators and apoptotic proteins.