Visit our Expo - Redox and Inflammation signaling 2012

Session XVI : Chemopreventive agents Poster XVI, 8
Epigallocatechin gallate inhibits phorbol ester-induced expression of COX-2 and
activation of NF-kappaB and CREB in mouse skin in vivo
Joydeb Kumar Kundu and Young-Joon Surh
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention,
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea
Despite accumulating evidence supporting the cancer chemopreventive properties of green
tea, the underlying molecular mechanisms are not fully clarified. The representative green tea
polyphenol epigallocatechin gallate (EGCG) has been reported to inhibit mouse skin tumor
promotion. Since an inappropriate expression of cyclooxygenase-2 (COX-2) has been
frequently implicated in the pathogenesis of cancer, we attempted to determine the effects of
EGCG on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in mouse
skin. EGCG administered by gavage inhibited COX-2 expression in TPA-treated mouse skin.
To further elucidate the underlying mechanisms of COX-2 inhibition, we examined the
effects of EGCG on the activation of different transcription factors that regulate COX-2
expression. While EGCG inhibited TPA-induced DNA binding of NF-kappaB and cyclic
AMP response element binding protein (CREB), the compound failed to block the activation
of AP-1 and CCAAT/enhancer binding protein (C/EBP) in TPA treated-mouse skin. EGCG
diminished TPA-induced phosphorylation and degradation of IkappaBalpha and nuclear
translocation of p65. Moreover, TPA-induced activation of extracellular signal-regulated
protein kinase and p38 mitogen-activated protein (MAP) kinase was suppressed by EGCG.
Pretreatment of mouse skin with pharmacological inhibitors of MAP kinases revealed that
SB203580, but not U0126, inhibited TPA-induced CREB DNA binding. Taken together, our
study indicates that EGCG inhibits TPA-induced COX-2 expression and activation of NF-!B
and CREB in mouse skin by downregulation of p38 MAP kinase.
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