Research Paper

Clinical & Experimental Metastasis

, Volume 29, Issue 2, pp 165-178

Gossypol inhibits growth, invasiveness, and angiogenesis in human prostate cancer cells by modulating NF-κB/AP-1 dependent- and independent-signaling

  • Jiahua JiangAffiliated withCancer Research Laboratory, Methodist Research Institute, Indiana University Health
  • , Veronika SlivovaAffiliated withCancer Research Laboratory, Methodist Research Institute, Indiana University Health
  • , Andrej JedinakAffiliated withCancer Research Laboratory, Methodist Research Institute, Indiana University Health
  • , Daniel SlivaAffiliated withCancer Research Laboratory, Methodist Research Institute, Indiana University HealthDepartment of Medicine, Indiana UniversityIndiana University Simon Cancer Center, School of Medicine, Indiana University Email author 

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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.

Keywords

Gossypol Cell cycle Invasion Migration Metastasis Angiogenesis NF-κB AP-1