Document Detail

Myricetin down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B.
MedLine Citation:
PMID:  17944529     Owner:  NLM     Status:  MEDLINE    
Abnormal expression of cyclooxygenase-2 (COX-2) has been implicated in the development of cancer. There are multiple lines of evidence that red wine exerts chemopreventive effects, and 3,5,4'-trihydroxy- trans-stilbene (resveratrol), which is a non-flavonoid polyphenol found in red wine, has been reported to be a natural chemopreventive agent. However, other phytochemicals might contribute to the cancer-preventive activities of red wine, and the flavonol content of red wines is about 30 times higher than that of resveratrol. Here we report that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, inhibits 12-O-tetradecanoylphorbol-13-acetate (phorbol ester)-induced COX-2 expression in JB6 P+ mouse epidermal (JB6 P+) cells by suppressing activation of nuclear factor kappa B (NF-kappaB). Myricetin at 10 and 20 microM inhibited phorbol ester-induced upregulation of COX-2 protein, while resveratrol at the same concentration did not exert significant effects. The phorbol ester-induced production of prostaglandin E 2 was also attenuated by myricetin treatment. Myricetin inhibited both COX-2 and NF-kappaB transactivation in phorbol ester-treated JB6 P+ cells, as determined using a luciferase assay. Myricetin blocked the phorbol ester-stimulated DNA binding activity of NF-kappaB, as determined using an electrophoretic mobility shift assay. Moreover, TPCK (N-tosyl-l-phenylalanine chloromethyl ketone), a NF-kappaB inhibitor, significantly attenuated COX-2 expression and NF-kappaB promoter activity in phorbol ester-treated JB6 P+ cells. In addition, red wine extract inhibited phorbol ester-induced COX-2 expression and NF-kappaB transactivation in JB6 P+ cells. Collectively, these data suggest that myricetin contributes to the chemopreventive effects of red wine through inhibition of COX-2 expression by blocking the activation of NF-kappaB.
Kyung Mi Lee; Nam Joo Kang; Jin Hee Han; Ki Won Lee; Hyong Joo Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-19
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  55     ISSN:  0021-8561     ISO Abbreviation:  J. Agric. Food Chem.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-07     Completed Date:  2008-01-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9678-84     Citation Subset:  IM    
Department of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul 151-921, Republic of Korea.
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MeSH Terms
Cell Line
Cyclooxygenase 2 / genetics*
Down-Regulation / drug effects*
Epidermis / enzymology
Flavonoids / pharmacology*
NF-kappa B / antagonists & inhibitors*
Tetradecanoylphorbol Acetate / pharmacology*
Wine / analysis
Reg. No./Substance:
0/Flavonoids; 0/NF-kappa B; 16561-29-8/Tetradecanoylphorbol Acetate; 529-44-2/myricetin; EC 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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