1186 SANGUINARINE IS A NOVEL INHIBITOR OF SURVIVIN AND INHIBITS THE GROWTH OF PROSTATE CANCER CELLS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research VI1 Apr 20101186 SANGUINARINE IS A NOVEL INHIBITOR OF SURVIVIN AND INHIBITS THE GROWTH OF PROSTATE CANCER CELLS Meng Sun, Jae Chun, Wei Lou, and Allen Gao Meng SunMeng Sun More articles by this author , Jae ChunJae Chun More articles by this author , Wei LouWei Lou More articles by this author , and Allen GaoAllen Gao More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.687AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer is a frequently occurring disease and is the second leading cause of cancer related deaths of men in the United States. Current treatments have proved inadequate in curing or controlling prostate cancer and a search for agents for the management of this disease is urgently needed. Survivin plays an important role in both progression of castration-resistant prostate cancer and resistance to chemotherapy. Altered expression of survivin in prostate cancer cells is associated with cancer progression, drug/radiation resistance, poor prognosis and short patient survival. METHODS We performed a cell based rapid screen of the Prestwick Chemical Library consisting of 1120 FDA-approved compounds with known safety and bioavailability in humans to identify potential inhibitors of survivin and anti-cancer agents for prostate cancer. RESULTS Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified as a novel inhibitor of survivin that selectively kills prostate cancer cells over ¡°normal¡± prostate epithelial cells. We found that sanguinarine inhibits survivin protein expression through protein degradation via the ubiquitin-proteasome system. Sanguinarine induces apoptosis and inhibits tumor formation and growth of human prostate cancer cells. Administration of sanguinarine, beginning 3 days post ectopic implantation of DU145 human prostate cancer cells, reduces both tumor weight and volume by more than 70% compared to the control treated mice with no apparent toxicity. In addition, sanguinarine sensitized prostate cancer cells to paclitaxel-mediated growth inhibition and apoptosis, offering a potential therapeutic strategy for overcoming taxol resistance. CONCLUSIONS These results suggest that sanguinarine may be developed as an agent either alone or in combination with taxol for treatment of castration-resistant prostate cancer overexpressing survivin. Sacramento, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e459 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Meng Sun More articles by this author Jae Chun More articles by this author Wei Lou More articles by this author Allen Gao More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...