Journal
CARCINOGENESIS
Volume 31, Issue 8, Pages 1442-1449Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgq099
Keywords
-
Categories
Funding
- Innovative Drug Research Center [R11-2007-107-01002-0]
- WCU
- National Research Foundation, Ministry of Education, Science and Technology, Republic of Korea [R31-008-000-10103-0]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available