title: Gossypol inhibits growth, invasiveness, and angiogenesis in human prostate cancer cells by modulating NF-κB/AP-1 dependent- and independent-signaling.
abstract: Although previous studies demonstrated anticancer activities of gossypol through the induction of apoptosis, the molecular mechanism(s) responsible for the inhibitory effects of gossypol on the metastatic behavior of cancer cells remain to be elucidated. Here, we show that gossypol inhibits growth of human prostate cancer cells through the modulation of cell cycle regulatory proteins. We also demonstrate that gossypol inhibits invasive behaviors (adhesion, migration, and invasion) and angiogenesis. These effects are mediated by the suppression of AP-1 and NF-κB activity, resulting in the inhibition of secretion of urokinase plasminogen activator and vascular endothelial growth factor, and the down-regulation of expression of chemokine receptor 4 in PC3 cells. In summary, our data suggest that gossypol could have potential therapeutic effect for the treatment of invasive prostate cancer.
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN 46202, USA. Jjiang2@iuhealth.org
authors.forename: Jiahua
authors.initials: J
authors.lastname: Jiang
authors.forename: Veronika
authors.initials: V
authors.lastname: Slivova
authors.forename: Andrej
authors.initials: A
authors.lastname: Jedinak
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
mesh_terms: D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D016193:G1 Phase; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D006072:Gossypol