https://scholars.lib.ntu.edu.tw/handle/123456789/564850
標題: | Prazosin displays anticancer activity against human prostate cancers: Targeting DNA and cell cycle | 作者: | Lin S.-C. SHIH-CHIEH CHUEH Hsiao C.-J. TSAI-KUN LI Chen T.-H. Liao C.-H. Lyu P.-C. JIH-HWA GUH |
公開日期: | 2007 | 卷: | 9 | 期: | 10 | 起(迄)頁: | 830-839 | 來源出版物: | Neoplasia | 摘要: | Quinazoline-based α1-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 α1-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 down-stream signaling cascades, including Cdc25c phosphorylation at Ser 216, nuclear export of Cdc25c, and cyclin-dependent kinase (Cdk) 1 phosphorylation at Tyr15. 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 tumormass 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. Copyright ? 2007 Neoplasia Press, Inc. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-35448965498&doi=10.1593%2fneo.07475&partnerID=40&md5=00e2ab70cce97f72b780fc67ea72e02b https://scholars.lib.ntu.edu.tw/handle/123456789/564850 |
ISSN: | 15228002 | DOI: | 10.1593/neo.07475 | SDG/關鍵字: | antineoplastic agent; caspase; cyclin A; cyclin B1; cyclin dependent kinase; doxazosin; phentolamine; prazosin; protein tyrosine phosphatase; serine; tamsulosin; terazosin; tyrosine; animal experiment; animal model; antineoplastic activity; apoptosis; article; cancer inhibition; cell cycle; cell cycle arrest; cell cycle G2 phase; concentration response; controlled study; DNA damage; DNA strand breakage; drug effect; drug efficacy; drug mechanism; drug potency; enzyme inactivation; gene targeting; human; human cell; in vivo study; mouse; nonhuman; priority journal; prostate cancer; protein phosphorylation; signal transduction; tumor xenograft |
顯示於: | 藥學系 |
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