Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 15
Sulforaphane inhibits phorbol ester-induced COX-2 expression in human breast
epithelial cells: I!B kinase # as a potential target
Ha-Na Kim, Eun-Hee Kim, Hye-Kyung Na, Young-Joon Surh
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention,
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea
Sulforaphane (SFN; 1-isothiocyanato-4-(methylsulfinyl)-butane), occurring naturally as a
precursor glucosinolate in cruciferous vegetables, is a member of the isothiocyanate family of
chemopreventive agents. Recent studies suggest that inflammation is causally linked to
carcinogenesis. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the biosynthesis of
prostaglandins, is inappropriately expressed in various cancers. In the present study, we
investigated the effect of SFN on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
COX-2 expression and underlying molecular mechanisms in human breast epithelial (MCF-
10A) cells. Treatment of MCF-10A cells with SFN (12.5 and 25 µM) significantly reduced
TPA-induced COX-2 expression. The DNA binding of NF-!B and degradation of IkappaBalpha
(I!B-") were suppressed by SFN in TPA-stimulated MCF-10A cells. SFN dosedependently
inhibited TPA-induced I!B kinas # (IKK#) activity. In addition, SFN inhibited
the phosphorylation of extracellular signal-regulated kinase (ERK) and the activity of ERK
and p38 mitogen-activated protein kinase (MAPK) in TPA-treated MCF-10A cells. U0126
and SB203580 that are specific inhibitors of ERK and p38 MAPK, respectively blunted TPAinduced
COX-2 expression. In conclusion, SFN inhibited TPA-induced COX-2 expression
and NF-!B activation in MCF-10A cells by targeting IKK# and MAPKs.
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