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Inflammatory mediator promotes colorectal cancer by stifling protective genes
Date:1/22/2012

HOUSTON - Chronic inflammation combines with DNA methylation, a process that shuts down cancer-fighting genes, to promote development of colorectal cancer, scientists at The University of Texas MD Anderson Cancer Center report today in the advance online publication of the journal Nature Medicine.

The team's connection of these two separate influences eventually may lead to better combination therapies for treating and preventing colorectal cancer.

In animal experiments, researchers found that prostaglandin E2, a chemical that promotes inflammation, accelerates the development of colorectal cancer by shutting down genes that suppress tumors and repair damaged DNA. They also found that while either an anti-inflammatory drug or a demethylating agent reduced the size and number of tumors in mice with colorectal cancer, the most powerful response occurred when both drugs were used together.

"We've known that chronic inflammation increases the risk of developing cancer and progression of disease," said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president at MD Anderson. "We've also known that tumor-suppressing genes are silenced in human colorectal cancer. However, nobody had made a molecular connection between these inflammatory mediators and changes in gene expression or silencing of genes through affects on DNA methylation."

Cancer prevention potential

The two drugs used in the animal experiments - the anti-inflammatory agent celecoxib (known commercially as Celebrex) and the demethylating agent azacitidine (Vidaza) - are both approved for human use.

"One potential application of our research would be a clinical trial for patients who are at extremely high risk for developing colorectal cancer, such as those with a genetic predisposition, to see if treatment with these agents would decrease their risk," DuBois said.

Prostaglandin E2 and methylation <
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Contact: Scott Merville
smerville@mdanderson.org
713-516-4855
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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