Skip Navigation LinksHome > May 25, 2014 - Volume 36 - Issue 10 > Key Steps Found Linking Dietary Fat and Colon Cancer Growth
Oncology Times:
doi: 10.1097/01.COT.0000450370.01186.39
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Key Steps Found Linking Dietary Fat and Colon Cancer Growth

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RAYMOND DUBOIS, MD, PHD
RAYMOND DUBOIS, MD, PHD
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New genetic evidence has been found that appears to strengthen the link between the role of dietary fats with colon cancer progression.

The study, led by Raymond DuBois, MD, PhD, Executive Director of Arizona State University's Biodesign Institute identified a peroxisome proliferator-activated receptor delta (PPAR delta), that, when deleted in a mouse model of colon cancer, stopped key steps required for the initiation and progression of tumor growth.

“This study has shown without a doubt that there is a new function for a key molecule, PPAR delta, in the initiation and progression of colon cancer,” he said in a news release. “These results also provide a new rationale for developing therapeutics that could block PPAR delta to treat inflammatory bowel disease and colorectal cancer.”

The study is available in the April 21 early online edition of the Proceedings of the National Academy of Sciences (http://www.pnas.org/cgi/doi/10.1073/pnas.1324233111).

As explained in a news release, evidence for the relationship comes from data showing that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the risk of developing colorectal cancer by 40 to 50 percent. NSAIDs target cyclooxygenase 2 (COX-2), which carries out steps to produce the pro-inflammatory molecule prostaglandin E2 (PGE2), found at high levels in colorectal tumors. DuBois' research team has long sought to uncover the key molecular steps regulating the COX-2/PGE2 pathway.

PPARs are central players in regulating the breakdown and storage of fats within a cell, and the team wanted to investigate the role that one molecule—PPAR delta—had on chronic inflammation and colorectal cancer progression.

In a mouse model of colon cancer, the team knocked out the gene to make PPAR, and found that the mice showed no clinical or cellular signs of chronic inflammation. Furthermore, when looking at the immune response, they found none of the usual immune cells associated with inflammation.

“We found that both PPAR and COX-2-derived PGE2 signaling coordinately promote tumorigenesis and is likely to be clinically relevant because the elevation of both PPAR delta and COX-2 in tumor tissues correlates with poor prognosis in colorectal cancer patients,” DuBois said in the news release. “This provides us with an important new clue in designing and developing a therapeutic arsenal to stop the initiation and progression of colon cancer.”

The research was supported in part by the National Colorectal Cancer Research Alliance, and the National Institutes of Health.

Wolters Kluwer Health | Lippincott Williams & Wilkins

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