NSAIDs induce 'suicide' in potentially cancerous intestinal cells

Date: Nov-04-2014 Nonsteroidal anti-inflammatory drugs protect against colorectal cancer by inducing "cell suicide" in intestinal stem cells that carry a mutated gene, according to researchers from the University of Pittsburgh Cancer Institute and the School of Medicine, both in Pittsburgh, PA.

Researchers have not previously been able to pinpoint the mechanism by which NSAIDs, such as aspirin, reduce colorectal cancer risk.

Previous animal studies and clinical trials have shown that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, lower the risk of developing intestinal polyps. These polyps can develop into cancer. However, researchers have not previously been able to pinpoint the mechanism by which NSAIDs reduce this cancer risk.

Lin Zhang, PhD, associate professor of the Department of Pharmacology and Chemical Biology at the Pitt School of Medicine and the University of Pittsburgh Cancer Institute, says the new study - published in the Proceedings of the National Academy of Sciences (PNAS) - has changed this:

"Our study identifies a biochemical mechanism that could explain how this preventive effect occurs," he says. "These findings could help us design new drugs to prevent colorectal cancer, which is the third leading cause of cancer-related deaths in the country."

In both animal models and samples from patients' tumors, Zhang's team found that NSAIDs activate the "death receptor pathway." This means that the drugs initiate suicide in intestinal stem cells that have a mutation in the APC gene.

The APC mutation makes these genes dysfunctional. Cells affected by the mutation can potentially develop into precancerous polyps and tumors. Although cells that have a mutation in the APC gene are targeted by NSAIDs, healthy cells with the non-mutated gene are unaffected.

Zhang says:

"We want to use our new understanding of this mechanism as a starting point to design better drugs and effective cancer prevention strategies for those at high risk of colon cancer. Ideally, we could harness the tumor-killing traits of NSAIDs and avoid possible side effects that can occur with their chronic use, such as gastrointestinal bleeding and ulcers."

In 2008, a study from researchers at the Cancer Center at the University of California-Irvine found that the combination of the NSAID sulindac and the targeted agent difluoromethylornithine reduces the risk of recurrent colorectal adenomas - an early sign of colon cancer - by 95%.

This combination therapy was also found to have the same level of side effects and toxicity as a placebo, making it a more attractive option than chemotherapy.

Lifestyle factors and colorectal cancer risk

More recently, Medical News Today looked at research demonstrating that the following lifestyle factors, when combined, lower the risk of colorectal cancer:

Keeping to a healthy weight
Not carrying a lot of fat around the belly
Exercising regularly
Not smoking
Limiting alcohol intake
Having a healthy diet.

Participants in the study who followed all five lifestyles had the lowest risk of developing cancer.
Compared with participants who only followed one of the healthy behaviors, participants who followed two, three, four or all five had a 13%, 21%, 34% and 37% lower risk of developing colorectal cancer, respectively.

Also, the researchers from that study found that there were more benefits for men than there were for women.

"Estimates based on our study populations suggest that up to 22% of the cases in men and 11% of the cases in women would have been prevented if all five of the healthy lifestyle behaviors had been followed," said lead author Dr. Krasimira Aleksandrova, from the German Institute of Human Nutrition Potsdam-Rehbrueck in Nuthetal.

"Our results particularly demonstrate the potential for prevention in men who are at a higher risk of bowel cancer than women," Dr. Aleksandrova concluded.

Written by David McNamee

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.