Chemopreventive properties of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis: down-regulation of cyclooxygenase-2, inducible nitric oxide synthase, and c-Jun. Cancer Res 2006 Mar 01;66(5):2853-9
Date
03/03/2006Pubmed ID
16510608Pubmed Central ID
PMC3015097DOI
10.1158/0008-5472.CAN-05-3279Scopus ID
2-s2.0-33645075440 (requires institutional sign-in at Scopus site) 113 CitationsAbstract
Our laboratory has used a rodent model of human esophageal squamous cell carcinoma to identify putative chemopreventive agents for this disease and to determine their mechanisms of action. In the present study, we treated F344 rats with the esophageal carcinogen, N-nitrosomethylbenzylamine (NMBA), thrice per week for 5 weeks. Beginning 1 week later, they were fed a synthetic diet containing 5% black raspberries (BRB) for the duration of the bioassay (25 weeks). Rats were sacrificed at weeks 9, 15, and 25. Esophageal tissues were collected, and tumor data were recorded. The expression and enzymatic activities of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of c-Jun in the esophagi, were evaluated to investigate the mechanism(s) by which black raspberries modulate tumorigenesis. At week 25, BRB inhibited tumor multiplicity, the standard end point in this tumor model, from 3.78 +/- 0.41 tumors per rat in NMBA-treated animals to 2.23 +/- 0.21 tumors per rat in animals treated with NMBA plus BRB (P < 0.005). BRB reduced mRNA and protein expression levels of COX-2, iNOS, and c-Jun as well as the level of prostaglandin E(2) in preneoplastic lesions of the esophagus at week 25. The berries inhibited mRNA expression of iNOS and c-Jun, but not COX-2, in papillomatous lesions of the esophagus. Prostaglandin E(2) and total nitrite levels were also decreased by BRB in papillomas. These results suggest a novel tumor suppressive role of BRB through inhibition of COX-2, iNOS, and c-Jun.
Author List
Chen T, Hwang H, Rose ME, Nines RG, Stoner GDMESH terms used to index this publication - Major topics in bold
AnimalsBody Weight
Carcinogens
Carcinoma, Squamous Cell
Cyclooxygenase 2
Diet
Dimethylnitrosamine
Dinoprostone
Down-Regulation
Eating
Esophageal Neoplasms
Fruit
JNK Mitogen-Activated Protein Kinases
Male
Nitric Oxide Synthase Type II
Nitrites
RNA, Messenger
Rats
Rats, Inbred F344
