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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2002, Volume21

124 pages

Issue price - $160.00

Effects of Yakuchinone A and Yakuchinone В on the Phorbol Ester-Induced Expression of COX-2 and iNOS and Activation of NF-kB in Mouse Skin

Kyung-Soo Chun
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea

Jee-Young Kang
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea

Ok Hee Kim
Korea Food and Drug Administration, Seoul, South Korea

Hoil Kang
Korea Food and Drug Administration, Seoul, South Korea

Young-Joon Surh, Ph.D., Professor
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy Seoul National University Shinlim-dong, Kwanak-gu Seoul 151-742 South Korea

ABSTRACT

Certain medicinal plants contain anti-inflammatory and antioxidative substances that can exert chemopreventive effects. Our previous studies have demonstrated that the methanol extract of Alpinia oxyphylla Miquel (Zingiberaceae) inhibits tumor promotion in mouse skin. Two major diarylheptanoids named yakuchinone A (l-[4'-hydroxy-3'-methoxyphenyl]-7-phenyl-3-heptanone) and yakuchinone В (l-[4'-hydroxy-3'-methoxyphenyl]-7-phenylhept-l-en-3-one) have been isolated from this medicinal plant. Both compounds have strong inhibitory effects on the synthesis of prostaglandins and leukotrienes in vitro. In the present work, we show that both yakuchinone A and yakuchinone В inhibit the expression of cyclooxygenase-2 (COX-2) and of inducible nitric oxide synthase (iNOS) as well as the expression of tumor necrosis factor (TNF)-a mRNA in mouse skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Topical application on mouse skin of these diarylheptanoids also attenuated the TPA-induced DNA binding activity of the ubiquitous eukaryotic transcription factor NF-kB that plays a crucial role in regulating the expression of the aforementioned proinflammatory enzymes and cytokines in response to a wide variety of external stimuli. These findings suggest that diarylheptanoids contained in Alpinia oxyphylla down-regulate COX-2 and iNOS expression through suppression of NF-kB activation in the TPA-treated mouse skin.