The
antioxidant 3,4',5 tri-hydroxystilbene (
resveratrol), a phytoalexin found in grapes, shows
cancer preventive activities, including inhibition of migration and invasion of metastatic
tumors. However, the molecular mechanism underlying the effect of
resveratrol on
tumor metastasis, especially in human metastatic lung and
cervical cancers is not clear. A non-cytotoxic dosage of
resveratrol causes a reduction in the generation of
reactive oxygen species, and suppresses
phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration in both A549 and HeLa cells.
Resveratrol also decreases both the expression and the enzymatic activity of
matrix metalloproteinase-9 (MMP-9), and the promoter activity of PMA-stimulated MMP-9 is also inhibited. However,
resveratrol does not affect either the expression or the proteolytic activity of MMP-2. Our results also show that
resveratrol suppresses the transcription of MMP-9 by the inhibition of both NF-κB and
AP-1 transactivation. These results indicate that
resveratrol inhibits both NF-κB and
AP-1 mediated MMP-9 expression, leading to suppression of migration and invasion of human metastatic lung and
cervical cancer cells.
Resveratrol has potential for clinical use in preventing invasion by human metastatic lung and
cervical cancers.