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
.