Carcinogenesis Advance Access published online on July 18, 2007
Carcinogenesis, doi:10.1093/carcin/bgm166
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Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids
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* Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Department of Gastroenterology, Virchow Campus, Charité University Medicine, Berlin, 13353, Germany
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
¶ To whom correspondences should be sent: Jing X. Kang, M.D., Ph.D., Massachusetts General Hospital, 149-13th Street, Room 4433, Charlestown, MA 02129, Tel: 617-726-8509, Fax: 617-726-6144, Email: jxkang{at}partners.org
Colorectal cancer is the second leading cause of cancer deaths in the United States. Anti-inflammatory drugs were shown to be effective in the prevention of colorectal cancer, supporting a link between inflammation and tumorigenesis in the colon. However, due to their side effects long-term administration of these drugs for colorectal cancer prevention is not feasible. An increased tissue content of omega-3 polyunsaturated fatty acids (n-3 PUFA) can dampen colon inflammation in animals as well as in humans. Whether increasing colon tissue n-3 PUFA alone is effective in preventing colon tumorigenesis remains to be investigated. Here we show that endogenously increased tissue levels of n-3 PUFA in the fat-1 transgenic mouse model lower incidence and growth rate of colon tumors induced by inflammation (dextrane sodium sulfate, DSS) plus treatment with carcinogen (azoxymethane, AOM). This was accompanied by lower activity of NF-
B, higher expression of transforming growth factor beta (TGF-ß) in the colons, and lower expression of inducible nitric oxide synthase (iNOS) in the tumors of fat-1 animals. Our data provide new insight into the mechanism by which n-3 PUFA suppress tumorigenesis through dampening of inflammation and NF-B activity. These results support a protective role of n-3 PUFA supplementation in the prevention of colorectal cancer.
Key Words: n-3 fatty acids • inflammation • colorectal cancer • tumorigenesis • fat-1 transgenic mice
The first two authors contributed equally to this study. Received March 23, 2007; revised July 9, 2007; accepted July 10, 2007.
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