https://scholars.lib.ntu.edu.tw/handle/123456789/193490
標題: | Prazosin Displays Anticancer Activity against Human Prostate Cancers: Targeting DNA and Cell Cycle. Prazosin對人類攝護腺癌細胞有抗癌活性:於dna 及細胞週期作用之分析 |
作者: | LIN, SSU-CHIA CHUEH, SHIH-CHIEH HSIAO, CHE-JEN LI, TSAI-KUN CHEN, TZU-HSUAN LIAO, CHO-HWA LYU, PING-CHIANG GUH, JIH-HWA 林思嘉 闕士傑 蕭哲仁 李財坤 陳姿璇 廖灼華 呂平江 顧記華 |
關鍵字: | prazosin;DNA damage;cell cycle;Cdc25c;mitochondria-involved apoptosis | 公開日期: | 2007 | 卷: | v.9 | 期: | n.10 | 起(迄)頁: | 830-839 | 來源出版物: | NEOPLASIA | 摘要: | Quinazoline-based alpha(1)-adrenoceptor antagonists, in particular doxazosin and terazosin, are suggested to display antineoplastic activity against prostate cancers. However, there are few studies elucidating the effect of prazosin. In this study, prazosin displayed antiproliferative activity superior to that of other alpha(1)-blockers, including doxazosin, terazosin, tamsulosin, and phentolamine. Prazosin induced G(2) checkpoint arrest and subsequent apoptosis in prostate cancer PC-3, DU-145, and LNCaP cells. In p53-null PC-3 cells, prazosin induced an increase in DNA strand breaks and ATM/ ATR checkpoint pathways, leading to the activation of downstream signaling cascades, including Cdc25 c phosphorylation at Ser 216, nuclear export of Cdc25c, and cyclin-dependent kinase (Cdk) 1 phosphorylation at Tyr(15). The data, together with sustained elevated cyclin A levels( other than cyclin B1 levels), suggested that Cdk1 activity was inactivated by prazosin. Moreover, prazosin triggered mitochondria-mediated and caspase-executed apoptotic pathways in PC-3 cells. The oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice. In summary, we suggest that prazosin is a potential antitumor agent that induces cell apoptosis through the induction of DNA damage stress, leading to Cdk1 inactivation and G2 checkpoint arrest. Subsequently, mitochondria-mediated caspase cascades are triggered to induce apoptosis in PC-3 cells. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/87971 |
顯示於: | 醫學系 |
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