Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which
piceatannol inhibits invasion and
metastasis. The aim of the current study was to investigate the effects of
piceatannol on the expression of
matrix metalloproteinase-9 (MMP-9) in DU145 human
prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to
tumor necrosis factor-α (TNF-α). However, treatment with
piceatannol reversed TNF-α- and MMP-9-induced
gelatin zymography and its gene expression. In addition, a
Matrigel invasion assay determined that
piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant
transcription factor that regulates numerous genes involved in
tumor cell invasion and
metastasis. Therefore, whether
piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that
piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor,
pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation.
Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of
piceatannol. The Akt inhibitor
LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that
piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145
prostate cancer cells.