Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids.
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-kappaB), 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-kappaB activity. These results support a protective role of n-3 PUFA supplementation in the prevention of CRC.
Nowak
Johannes
J
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Weylandt
Karsten H
KH
Habbel
Piet
P
Wang
Jingdong
J
Dignass
Axel
A
Glickman
Jonathan N
JN
Kang
Jing X
JX
D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D003092:Colitis / Q000150:complications*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D044943:Fatty Acid Desaturases / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005819:Genetic Markers; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014481:United States / Q000453:epidemiology
D029742:Caenorhabditis elegans Proteins; D004273:DNA, Neoplasm; D015525:Fatty Acids, Omega-3; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes