782 SANGUINARINE INHIBITS STAT3 ACTIVATION AND TUMOR GROWTH IN PROSTATE CANCER CELLS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2012782 SANGUINARINE INHIBITS STAT3 ACTIVATION AND TUMOR GROWTH IN PROSTATE CANCER CELLS Meng Sun, Chengfei Liu, Wei Lou, Nagalakshmi Nadiminty, Joy Yang, Christopher Evans, and Allen Gao Meng SunMeng Sun Sacramento, CA More articles by this author , Chengfei LiuChengfei Liu Sacramento, CA More articles by this author , Wei LouWei Lou Sacramento, CA More articles by this author , Nagalakshmi NadimintyNagalakshmi Nadiminty Sacramento, CA More articles by this author , Joy YangJoy Yang Sacramento, CA More articles by this author , Christopher EvansChristopher Evans Sacramento, CA More articles by this author , and Allen GaoAllen Gao Sacramento, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.870AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogenic transcription factor implicated in prostate carcinogenesis and progression. Stat3 activation is associated with prostate cancer development and progression. Constitutively activated Stat3 activates androgen receptor signaling and promotes castration-resistant prostate cancer growth. Targeting Stat3 activation is an effective strategy in prostate cancer therapy. METHODS DU145, C4-2B and LNCaP cells were treated with sanguinarine for 4 hours and then stimulated with Interleukin-6 (IL-6) or vehicle. The phosphorylation status of STAT3 and related proteins were measured with western blots. Activation of transcription by STAT3 via the STAT3 responsive element was measured with luciferase reporter assay. The effect of sanguinarine on DU145 and LN/S17 cells anchorage-independent growth were examined with soft agar assay. The effect of sanguinarine on cells migration and invasion of DU145 cells were measured with scratch assay and invasion assay respectively. RESULTS Exposure to micromolar concentrations of sanguinarine resulted in suppression of constitutive as well as IL6-induced phosphorylation of STAT3 at both Tyr705 and Ser727 in DU145 cells. The inhibition of STAT3 phosphorylation correlated with the inhibition of Janus-activated Kinase 2 (JAK2) and src phosphorylation. Sanguinarine inhibited the constitutive and IL6-induced STAT3 responsive element luciferase activities. Several STAT3 regulated genes such as c-myc and survivin were downregulated by sanguinarine. We found that sanguinarine inhibited the migration and invasion of DU145 cells that express constitutively activated STAT3. Furthermore, sanguinarine inhibited the anchorage-independent growth of DU145 and LN/S17 cells and suppressed the growth of DU145 xenografts in nude mice. CONCLUSIONS These data suggest that sanguinarine targets multiple upstream kinases that mediate STAT3 activity. Sanguinarine is a potent STAT3 inhibitor that could be developed as a therapeutic agent for prostate cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e320 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Meng Sun Sacramento, CA More articles by this author Chengfei Liu Sacramento, CA More articles by this author Wei Lou Sacramento, CA More articles by this author Nagalakshmi Nadiminty Sacramento, CA More articles by this author Joy Yang Sacramento, CA More articles by this author Christopher Evans Sacramento, CA More articles by this author Allen Gao Sacramento, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...