Carcinogenesis Advance Access originally published online on July 18, 2007
Carcinogenesis 2007 28(9):1991-1995; 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
1 Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
2 Department of Gastroenterology, Virchow Campus, Charité University Medicine, Berlin, 13353, Germany
3 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
* To whom correspondence should be addressed. Massachusetts General Hospital, 149-13th Street, Room 4433, Charlestown, MA 02129, USA. Tel: +1 617 726 8509; Fax: +1 617 726 6144; Email: jxkang{at}partners.org
Colorectal cancer (CRC) is the second leading cause of cancer deaths in USA. Anti-inflammatory drugs were shown to be effective in the prevention of CRC, supporting a link between inflammation and tumorigenesis in the colon. However, due to their side effects, long-term administration of these drugs for CRC 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) plus treatment with carcinogen (azoxymethane). This was accompanied by lower activity of nuclear factor kappa B (NF-
B), higher expression of transforming growth factor beta in the colons and lower expression of inducible nitric oxide synthase in the tumors of fat-1 animals. Our data provide new insight into the mechanism by which n-3 PUFA suppresses tumorigenesis through dampening of inflammation and NF-B activity. These results support a protective role of n-3 PUFA supplementation in the prevention of CRC.
Abbreviations: AOM, azoxymethane; CRC, colorectal cancer; DSS, dextrane sodium sulfate; iNOS, inducible nitric oxide synthase; n-3-PUFA, omega-3 polyunsaturated fatty acids; NF-B, nuclear factor kappa B; PCR, polymerase chain reaction; TGF-ß, transforming growth factor beta; WT, wild-type
These two authors contributed equally to this study. Received March 23, 2007; revised July 9, 2007; accepted July 10, 2007.
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