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Ellagic acid coordinately attenuates Wnt/β-catenin and NF-κB signaling pathways to induce intrinsic apoptosis in an animal model of oral oncogenesis.
MedLine Citation:
PMID:  22160170     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Constitutive activation of the Wnt signaling pathway and its downstream effectors plays a key role in neoplastic transformation. The objective of this study was to investigate the effect of ellagic acid, a plant-derived polyphenol on Wnt/β-catenin signaling and its downstream circuits- NF-κB and mitochondrial apoptosis in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model. METHODS: Hamsters were divided into six groups. The right buccal pouches of animals in groups 1-4 were painted with 0.5% DMBA three times a week for 14 weeks. Animals in groups 2-4 received in addition basal diet containing ellagic acid at a concentration of 0.1, 0.2, and 0.4% in the diet. Group 5 animals were given 0.4% ellagic acid alone. Group 6 animals served as control. The expression of the members of Wnt and NF-κB signaling and intrinsic apoptosis was evaluated by western blot analysis. RESULTS: Dietary supplementation of 0.4% ellagic acid suppressed the development of HBP carcinomas by preventing the constitutive activation of Wnt pathway through the downregulation of Fz, Dvl-2, GSK-3β and nuclear translocation of β-catenin. Abrogation of Wnt signaling by ellagic acid was also associated with inactivation of NF-κB and modulation of key components of the mitochondrial apoptotic network. CONCLUSIONS: Our findings suggest a functional crosstalk between Wnt and NF-κB signaling pathways in HBP carcinomas that is blocked by ellagic acid supplementation. Dietary ellagic acid that targets the Wnt/β-catenin pathway as well as its downstream signaling mediators is a unique candidate for cancer chemoprevention.
Authors:
Prabukumar Anitha; Ramamurthi Vidya Priyadarsini; Krishnamurthy Kavitha; Paranthaman Thiyagarajan; Siddavaram Nagini
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-11
Journal Detail:
Title:  European journal of nutrition     Volume:  -     ISSN:  1436-6215     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888704     Medline TA:  Eur J Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Chidambaram, Tamil Nadu, 608 002, India.
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