Resveratrol inhibits tumor cell adhesion to endothelial cells by blocking ICAM-1 expression

Area of Science:

• Molecular Biology
• Cancer Research
• Pharmacology

Background:

• Resveratrol, a polyphenol found in grapes, possesses potential anti-inflammatory, cardioprotective, and cancer-preventive properties.
• The precise mechanisms underlying resveratrol's biological effects, particularly in cancer, remain incompletely understood.
• Tumor cell adhesion to endothelial cells is a critical early step in the process of cancer metastasis.

Purpose of the Study:

• To investigate whether resveratrol can inhibit tumor cell adhesion to endothelial cells.
• To elucidate the molecular mechanisms by which resveratrol mediates this inhibition, focusing on cell adhesion molecules and transcription factors.

Main Methods:

• Human fibrosarcoma HT1080 cells and endothelial ECV304 cells were used to model tumor cell-endothelial cell adhesion.
• Phorbol 12-myristate 13-acetate (PMA) was used to induce cell adhesion and expression of adhesion molecules.
• Resveratrol's effects on cell adhesion, ICAM-1, VCAM-1, E-selectin expression, and NF-kappaB activation were assessed using techniques including RT-PCR, flow cytometry, ELISA, and luciferase assays.

Main Results:

• Resveratrol significantly inhibited PMA-induced adhesion of HT1080 cells to ECV304 cells in a dose-dependent manner.
• PMA treatment increased ICAM-1 expression in HT1080 cells, which was reduced by resveratrol.
• Resveratrol suppressed PMA-induced activation of the transcription factor NF-kappaB and NF-kappaB-dependent transcriptional activity.

Conclusions:

• Resveratrol demonstrates an anti-metastatic potential by inhibiting tumor cell adhesion to endothelial cells.
• This effect is mediated through the suppression of NF-kappaB activation and subsequent reduction in ICAM-1 expression.
• These findings highlight a potential therapeutic role for resveratrol in preventing cancer metastasis.