Visit our Expo - Redox and Inflammation signaling 2012

Session XVI : Chemopreventive agents Poster XVI, 6
Combined effects of gallic acid and resveratrol on gap junction intercellular
communication and matrix metalloproteinase
Jong Hoon Kim, Ki Won Lee, Hyo Jin Kim, and Hyong Joo Lee*
Department of Food Biotechnology, School of Agricultural Biotechnology, and Center
for
Agricultural Biomaterials, Seoul National University, Seoul 151-742, Republic of Korea
Dietary or pharmaceutical augmentation of endogenous antioxidant defense capacity has been
considered one of the plausible ways to prevent reactive oxygen species (ROS)-mediated
human diseases and aging, but antioxidant therapy has been at best equivocal. The present
study investigated the possible combined effect of gallic acid and resveratrol, which is major
antioxidants in red wine, on gap junction intercellular communication (GJIC) and on matrix
metalloproteinase-2 (MMP-2) closely related to carcinogenesis. Resveratrol, but not gallic
acid, prevented inhibition of GJIC and hyperphosphorylation of connexin 43 (Cx43) induced
by hydrogen peroxide (H2O2) in normal rat liver epithelial cells. The sustained production of
H2O2 by phenazine methosulfate (PMS), a chemical generating intracellular ROS, induced
activation of MMP-2 in HT1080 human fibrosarcoma cells. Resveratrol prevented activation
of pro-MMP-2 by PMS, but gallic acid did not exert these effects. Gallic acid rather induced
inhibition of GJIC and activation of MMP-2 without H2O2 in a dose-dependent manner. Both
GA and resveratrol generated H2O2 in the media without cells, and GA generated almost 5
times more H2O2 than resveratrol in a dose- and time-dependant manner. The inhibition of
GJIC by gallic acid was mediated by hyperphosphorylation of connexin 43 (Cx43) and
activation of extracellular signal-regulated kinase 1/2 (ERK1/2) through generation of ROS,
while catalase and resveratrol significantly reversed gallic acid-induced inhibition of GJIC.
The activation of MMP-2 and increase of motility by gallic acid was also partly abolished by
catalase and resveratol. These results indicate potential prooxidant activity of gallic acid and
the combined effect of red wine phenolics on carcingenesis. Taken together, above findings
suggest that antioxidants may act differently in ROS-mediated carcinogenesis depending on
the conditions and structure.
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