title: Resveratrol inhibits tumor cell adhesion to endothelial cells by blocking ICAM-1 expression.
abstract: 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-kappaB, the effects of resveratrol on the activation of this factor in HT1080 cells was also investigated. Resveratrol inhibited the PMA-induced NF-kappaB activation and NF-kappaB-dependent luciferase activity. These results suggest that resveratrol may exert an antimetastatic effect by inhibiting NF-kappaB activation and ICAM-1 expression, leading to suppression of tumor cell adhesion to endothelial cells.
authors.affiliation: The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Chonnam National University Medical School, Kwangju, Korea.
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Ki Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Mi Ha
authors.initials: MH
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Chang
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Baek
authors.forename: Seok Mo
authors.initials: SM
authors.lastname: Kim
authors.forename: Young Do
authors.initials: YD
authors.lastname: Jung