TY - JOUR T1 - Resveratrol Inhibits Tumor Cell Adhesion to Endothelial Cells by Blocking ICAM-1 Expression JF - Anticancer Research JO - Anticancer Res SP - 355 LP - 362 VL - 29 IS - 1 AU - JUNG SUN PARK AU - KI MIN KIM AU - MI HA KIM AU - HEE JUNG CHANG AU - MIN KYUNG BAEK AU - SEOK MO KIM AU - YOUNG DO JUNG Y1 - 2009/01/01 UR - http://ar.iiarjournals.org/content/29/1/355.abstract N2 - Resveratrol, a grape polyphenol, is thought to have anti-inflammatory, cardioprotective, and cancer preventive properties. However, the mechanisms by which resveratrol might produce these effects are not clearly defined. A study was performed on whether resveratrol could prevent tumor cells from adhering to endothelial cells, which is an essential step during tumor metastasis. Phorbol 12-myristate 13-acetate (PMA) induced human fibrosarcoma HT1080 cells to adhere to endothelial ECV304 cells. Resveratrol inhibited PMA-induced HT1080 cells adhesion in a dose-dependent manner. To further study the mechanisms of this resveratrol-mediated blockade of tumor cell adhesion, the expression of the cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were examined. PMA induced ICAM-1 expression in HT1080 cells. In contrast, the expression of VCAM-1 and E-selectin were not altered by PMA treatment. The increase in tumor cell adhesion to endothelial cells following PMA treatment was partially inhibited by ICAM-1 siRNA or neutralizing antibodies. Resveratrol reduced the PMA-induced ICAM-1 expression in HT1080 cells as determined by RT-PCR, flow cytometry and ELISA. As the induction of ICAM-1 requires activation of the transcription factor NF-κB, the effects of resveratrol on the activation of this factor in HT1080 cells was also investigated. Resveratrol inhibited the PMA-induced NF-κB activation and NF-κB-dependent luciferase activity. These results suggest that resveratrol may exert an anti-metastatic effect by inhibiting NF-κB activation and ICAM-1 expression, leading to suppression of tumor cell adhesion to endothelial cells. Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -