Parthenolide Induces Apoptosis and Cell Cycle Arrest of Human 5637 Bladder Cancer Cells In Vitro 英文参考文献.docVIP

Molecules 2011, 16, 6758-6768; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Parthenolide Induces Apoptosis and Cell Cycle Arrest of Human 5637 Bladder Cancer Cells In Vitro Guang Cheng and Liping Xie * Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China * Author to whom correspondence should be addressed; E-Mail: lipxie@; Tel: +86-571 Fax: +86-571 Received: 20 June 2011; in revised form: 30 July 2011 / Accepted: 2 August 2011 / Published: 9 August 2011 Abstract: Parthenolide, the principal component of sesquiterpene lactones present in medical plants such as feverfew (Tanacetum parthenium), has been reported to have anti-tumor activity. In this study, we evaluated the therapeutic potential of parthenolide against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with parthenolide resulted in a significant decrease in cell viability. Parthenolide induced apoptosis through the modulation of Bcl-2 family proteins and poly (ADP-ribose) polymerase degradation. Treatment with parthenolide led to G1 phase cell cycle arrest in 5637 cells by modulation of cyclin D1 and phosphorylated cyclin-dependent kinase 2. Parthenolide also inhibited the invasive ability of bladder cancer cells. These findings suggest that parthenolide could be a novel therapeutic agent for treatment of bladder cancer. Keywords: bladder cancer; parthenolide; cell cycle arrest; apoptosis 1. Introduction Bladder cancer is the fourth most common cancer in the USA, with an expected 71,000 newly diagnosed cases and 14,300 deaths [1] in 2009. It has the highest lifetime treatment cost of any cancer because of the need for frequent interval cystourethroscopy, urine cytology, and radiological