S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF-κB activation and cyclooxygenase-2 expression in human breast epithelial cells: Cysteine 179 of IKKβ as a potential target
|dc.identifier.citation||Carcinogenesis, Vol.31 No.8, pp.1442-1449||-|
|dc.description.abstract||There are multiple lines of evidence supporting that chronic inflammation is linked to carcinogenesis. Nuclear factor-kappa B (NF-kappa B), a major redox-sensitive transcription factor responsible for the induction of a wide array of pro-inflammatory genes, is frequently overactivated in many tumors. Moreover, constitutive activation of I kappa B kinase (IKK), a key regulator of NF-kappa B signaling, has been implicated in inflammation-associated tumorigenesis. Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene; PIC) derived from grapes, rhubarb and sugarcane exhibits immunosuppressive and antitumorigenic activities in several cell lines, but the underlying mechanisms are poorly understood. In the present study, we found that PIC inhibited migration and anchorage-independent growth of human mammary epithelial cells (MCF-10A) treated with the prototypic tumor promoter, 12-O-tetradecanoylphorbol-13-aceate (TPA). PIC treatment suppressed the TPA-induced activation of NF-kappa B and expression of cyclooxygenase-2 (COX-2) in MCF-10A cells. We speculate that an electrophilic quinone formed as a consequence of oxidation of PIC bearing the catechol moiety may directly interact with critical cysteine thiols of IKK beta, thereby inhibiting its catalytic activity. In support of this speculation, the reducing agent dithiothreitol abrogated the inhibitory effects of PIC on TPA-induced activation of NF-kappa B signaling and expression of COX-2. In addition, the inhibitory effects of PIC on NF-kappa B activation and COX-2 induction were blunted in cells expressing mutant IKK beta (C179A) in which cysteine 179 was replaced by alanine. In conclusion, our results show that direct modification of IKK beta by PIC, presumably at the cysteine 179 residue, blocks NF-kappa B activation signaling and COX-2 induction in TPA-treated MCF-10A cells and also migration and transformation of these cells.||-|
|dc.title||Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF-κB activation and cyclooxygenase-2 expression in human breast epithelial cells: Cysteine 179 of IKKβ as a potential target||-|
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