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Cytotoxic effects of escin on human castration-resistant prostate cancer cells through the induction of apoptosis and G2/M cell cycle arrest
인체 호르몬불응성 전립선암 세포주에서 Escin의 세포고사 및 세포주기 억제 기전에 관한 연구

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Authors
PIAO SONGZHE
Advisor
김현회
Major
의과대학 의학과
Issue Date
2014-08
Publisher
서울대학교 대학원
Keywords
EscinCastration-Resistant Prostate CancerApoptosisCell Cycle
Description
학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2014. 8. 김현회.
Abstract
The progression of prostate cancer to the lethal castration-resistant stage coincides with the high mortality and poor outcome due to loss of successful treatment options and requires the discovery of more potent agents. Escin is known to have cytotoxic
effects on several tumor types, but little is known in the context of prostate cancer. The aim of the present study was to investigate the effects of escin on human castration- resistant prostate cancer (CRPC) cells, PC-3 and DU-145, both in vitro and in vivo.
The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and a western blot. The in vivo efficacy of escin in PC-3 and DU-145 cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice.
The treatment with escin significantly reduced cell viability of PC-3 and DU-145 cells in a dose- and time-dependent manner. In both PC-3 and DU-145 cells, treatment with escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (Bax,cleaved-caspase3, and cleaved-PARP) proteins and decreases in anti-apoptotic (XIAP, cIAP-1, cIAP-2,Bcl-2, and Bcl-xL) proteins. In both PC-3 and DU-145 cells, escin treatment caused G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclin B1 and its activating partner CDK1, with the concomitant induction of p21WAF1/CIP1. In addition, escin significantly inhibited the growth of PC-3 and DU-145 cells xenografts subcutaneously established in BALB/c nude mice
In sum, this study provides evidence that escin not only induced cytotoxic effects on PC-3 and DU-145 cells through the induction of apoptosis and G2/M cell cycle
arrest, but also suppressed tumor growth in xenograft models, in support of its efficacious potential as a novel therapeutic agent for CRPC.
Language
English
URI
https://hdl.handle.net/10371/122009
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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