Aerodigestive malignancies affect over 180,000 Americans yearly. In advanced stages there is a less than 50% five-year disease-specific survival. These malignancies are characterized by genotoxic damage in addition to injury response and chronic inflammatory states that are characterized by early response gene activation events including constitutive NF kappa B activation. Resveratrol is a potent antioxidant with cancer-preventive properties. The mechanism by which resveratrol imparts cancer chemopreventive effects is not clearly defined but may involves inhibiting NF kappa B activation. In the present study we explored the effects of resveratrol and indomethacin on cell proliferation and NF kappa B activity in rhek-keratinocytes. First, the rhek parental cell line was evaluated for basal and inducible NF kappa B luciferase activity after resveratrol and indomethacin incubation. We found that indomethacin, but not resveratrol, had the ability to downregulate basal NF kappa B luciferase activity in rhek parental cells at 24 hours. However, 5-20uM of resveratrol was more effective than indomethacin in downregulating inducible NF kappa B luciferase activity. Next, cell proliferation was evaluated by MTT assay. 20 uM of resveratrol was very effective in its ability to decrease cell proliferation in rhek clones that overexpressed NF kappa B, but was less effective than in rhek cells with low NF kappa B constitutive activation. We conclude that resveratrol can prevent NF kappa B activation by PMA. We also conclude that resveratrol can inhibit rhek cell proliferation. It is known that indomethacin can exert effects on NF kappa B at the level of the upstream kinases, but since there is a difference of effect between indomethacin and resveratrol on constitutive NF kappa B activation we conclude that they act by different mechanisms.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]