Gossypol suppresses invasive behavior of human prostate cancer cells by modulating AP‐1 and NF‐kappaB signaling pathways

Abstract

Gossypol (GP) is a naturally occurring yellow pigment present in cottonseed that was originally identified as a potent anti‐fertility agent in both men and women. As previously demonstrated, GP suppresses proliferation of a variety of cancer cells in vitro and in vivo through the mechanism including the induction of apoptosis. However, the molecular mechanism(s) responsible for the inhibitory effects of GP on the metastatic behavior of human prostate cancer cells remain to be elucidated. In the present study, we used DNA‐microarray, reporter gene assay, Western blot analysis and ELISA to investigate the effects of GP on the invasiveness of human prostate cancer cells PC3. Here, we show that GP inhibits the cell adhesion, cell migration, and cell invasion of PC3 cells. Moreover, GP suppresses the NF‐kB activity in PC3 cells by the down‐regulation of the expression of p65/p50, while AP‐1 activity is inhibited by the down‐regulation of the expression of c‐fos. The inhibition of AP‐1 and NF‐kB activity results in the modulation of cell cycle regulatory proteins and inhibition of the secretion of vascular endothelial growth factor (VEGF). Collectively, our findings suggest that GP exerts its effects on cancer cells by multiple mechanisms and may have potential therapeutic use for the treatment of prostate cancer.