Piceatannol inhibits migration and invasion of prostate cancer cells: possible mediation by decreased interleukin-6 signaling

• Published in: The Journal of nutritional biochemistry 2012-03, Vol.23 (3), p.228-238
• Main Authors: Kwon, Gyoo Taik, Jung, Jae In, Song, Hye Rim, Woo, Eun Young, Jun, Jong-Gab, Kim, Jin-Kyung, Her, Song, Park, Jung Han Yoon
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Line, Tumor; Epidermal Growth Factor - drug effects; Epidermal Growth Factor - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humans; Interleukin-6; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; Interleukin-6 - secretion; Male; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Inbred BALB C; Neoplasm Metastasis - drug therapy; Neoplasm Metastasis - pathology; Phosphorylation; Piceatannol; Prostate cancer cells; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Rheum; Signal Transduction - drug effects; STAT3; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Stilbenes - pharmacology; Urokinase-Type Plasminogen Activator - genetics; Urokinase-Type Plasminogen Activator - metabolism; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitaceae
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2010.11.019

Piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) is a polyphenol detected in grapes, red wine and Rheum undulatum; it has also 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 epidermal growth factor (EGF)-induced migration and invasion of DU145 cells, in addition to the migration of MLL, PC3 and TRAMP-C2 prostate cancer cells. In DU145 cells, piceatannol attenuated the secretion and messenger RNA levels of matrix metalloproteinase-9, urokinase-type plasminogen activator (uPA) and vascular endothelial growth factor (VEGF). Piceatannol increased the protein levels of tissue inhibitor of metalloproteinase-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 interleukin (IL)-6 secretion. An IL-6 neutralizing antibody inhibited EGF-induced STAT3 phosphorylation and EGF-stimulated migration of DU145 cells. Interleukin-6 treatment was also shown to enhance the secretion of uPA and VEGF, STAT3 phosphorylation and the migration of DU145 cells; these increases were suppressed by piceatannol. 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.