Wine phenolic antioxidants inhibit AP-1 transcriptional activity

Some of the beneficial effects of moderate wine consumption may be related to the antioxidant properties of polyphenolic compounds containing tannins, flavonoids, and phenolic acids. Cellular actions have recently been report ed and may involve the modulation of transcriptional factors such as AP-1 ( activator protein-1), which controls the expression of various genes implic ated in inflammation processes, cell differentiation, and proliferation. Th e aim of this study was to evaluate the modulation of AP-1 activity by the phenolic acids (gallic, caffeic, protocatechic, paracoumaric, sinapic, and ferulic acids) that are present in wine and to compare their modulating pat hways to those of lipophilic or hydrophilic "chain-breaking" antioxidants ( such as DL-alpha -tocopherol or trolox) vitamin C, nitric oxide, and reduce d glutathione. AP-1 response was studied on a cell line (MTLN) derived from MCF-7 cells transfected with luciferase gene under TRE sequence control. A fter stimulation by phorbol 12-myristate 13-acetate (PMA; 100 nM, 6 h, 10(- 7) M), luciferase activity was determined by a luminescence method in the p resence of luciferine/coenzyme A solution using a luminometer (LKB 1251, Fi nland). Antioxidants to be tested were incubated with cells in the presence or absence of PMA. Stimulation with PMA resulted in an AP-1-mediated incre ase in luciferase gene expression corresponding to an 8-fold increase in lu ciferase activity. After stimulation by PMA, a dose-dependent inhibition of AP-1 was observed with the six phenolic acids in the 20 nm-20 muM concentr ation range: gallic acid > caffeic > protocatechic, paracoumaric, sinapic a cids > ferulic acid. Inhibition was more pronounced with phenolic acids tha n with DL-a-tocopherol (IC50 = 5 +/- 4.5 muM. for gallic, acid vs 85 +/- 11 muM. for vitamin E). None of the hydrophilic antioxidants inhibited PMA-in duced AP-1 activation. None of the antioxidants tested in the absence of PM A stimulation induced any activation or inhibition of AP-1. Our results sug gest that phenolic acids may act directly on cell signaling via inhibition of AP-1 transcriptional activity. In addition to preventing LDL oxidation i n the arterial wall, our observations indicate that phenolic acids have a c ell-mediated capacity to prevent some of the processes involved in atherosc lerosis in a plasma concentration range compatible with nutritional intakes .