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KMID : 1161420120150030253
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Journal of Medicinal Food
2012 Volume.15 No. 3 p.253 ~ p.257
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Phloretin Inhibits Phorbol Ester?Induced Tumor Promotion and Expression of Cyclooxygenase-2 in Mouse Skin: Extracellular Signal-Regulated Kinase and Nuclear Factor-κB as Potential Targets
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Shin Jun-Wan
Kundu Joydeb Kumar
Surh Young-Joon
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Abstract
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The present study investigated the effect of phloretin [2′,4′,6′-trihydroxy-3-(4-hydroxyphenyl)-propiophenone] on 12-O-tetradecanoylphorbol 13-acetate (TPA)?induced cyclooxygenase-2 (COX-2) expression and tumor promotion in mouse skin and explored the underlying molecular mechanisms. Topical application of phloretin significantly inhibited 7,12-dimethylbenz[a]anthracene-initiated and TPA-promoted mouse skin carcinogenesis. Pretreatment with phloretin on the dorsal skin of mice inhibited TPA-induced COX-2 expression in a dose-dependent manner. To elucidate the molecular mechanism underlying COX-2 inhibition by phloretin, we examined its effect on TPA-induced activation of nuclear factor-κB (NF-κB), a ubiquitous transcription factor responsible for TPA-induced COX-2 expression in mouse skin. Topically applied phloretin decreased the TPA-induced DNA binding of NF-κB. In addition, phloretin inhibited the phosphorylation as well as the catalytic activity of extracellular signal-regulated kinase (ERK), which was previously found to activate NF-κB and induce COX-2 expression in TPA-treated mouse skin. Taken together, the inhibitory effects of phloretin on TPA-induced NF-κB activation and COX-2 expression through the modulation of ERK signaling may partly account for its antitumor-promoting effect on mouse skin carcinogenesis.
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KEYWORD
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chemoprevention, cyclooxygenase-2, mouse skin carcinogenesis, nuclear factor-κB, phloretin
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