Resveratrol inhibits tumor cell adhesion to endothelial cells by blocking ICAM-1 expression.
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.
Park
Jung Sun
JS
The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Chonnam National University Medical School, Kwangju, Korea.
Kim
Ki Min
KM
Kim
Mi Ha
MH
Chang
Hee Jung
HJ
Baek
Min Kyung
MK
Kim
Seok Mo
SM
Jung
Young Do
YD