Oral administration of piceatannol inhibits the lung metastasis of prostate cancer cells

Abstract

Piceatannol (trans‐3,4,3′,5′‐tetrahydroxystilbene) is a polyphenol detected in grapes, red wine, and Rheum undulatum; it has been demonstrated to exert anticarcinogenic effects. In this study, in order to determine whether piceatannol inhibits the lung metastasis of prostate cancer cells, MAT‐Ly‐Lu (MLL) rat prostate cancer cells expressing luciferase were injected into the tail veins of male nude mice. The oral administration of piceatannol (20 mg/kg) significantly inhibited the accumulation of MLL cells in the lungs of these mice. In the cell culture studies, piceatannol was demonstrated to inhibit the basal and EGF‐induced migration and invasion of DU145 human prostate cancer cells. Piceatannol attenuated the mRNA levels and secretion of MMP‐9, uPA and VEGF and increased the protein levels of TIMP‐2 in a concentration‐dependent fashion. Additionally, piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT)3. Furthermore, piceatannol effected reductions in both basal and EGF‐induced IL‐6 secretion. An IL‐6 neutralizing antibody inhibited EGF‐induced STAT3 phosphorylation and EGF‐stimulated migration of DU145 cells. These results demonstrate that the inhibition of IL‐6/STAT3 signaling may constitute a mechanism by which piceatannol regulates the expression of proteins involved in regulating the migration and invasion of DU145 cells.