期刊
EUROPEAN JOURNAL OF NUTRITION
卷 52, 期 1, 页码 75-84出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00394-011-0288-y
关键词
Apoptosis; Chemoprevention; Ellagic acid; Hamster buccal pouch; NF-kappa B; Wnt
资金
- Department of Biotechnology, New Delhi, India under the 7th FP of the Indo-EU Joint Collaborative Project on 'FUNCFOOD'
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/beta-catenin signaling and its downstream circuits- NF-kappa B and mitochondrial apoptosis in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model. 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-kappa B signaling and intrinsic apoptosis was evaluated by western blot analysis. 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-3 beta and nuclear translocation of beta-catenin. Abrogation of Wnt signaling by ellagic acid was also associated with inactivation of NF-kappa B and modulation of key components of the mitochondrial apoptotic network. Our findings suggest a functional crosstalk between Wnt and NF-kappa B signaling pathways in HBP carcinomas that is blocked by ellagic acid supplementation. Dietary ellagic acid that targets the Wnt/beta-catenin pathway as well as its downstream signaling mediators is a unique candidate for cancer chemoprevention.
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