The researchers examined expression of 11βHSD2 in human colon polyps and in the colons of mice predisposed to colon cancer. They found that 11βHSD2 was increased in polyps found in both mice and humans and correlated with COX-2 expression and activity.
They then inhibited 11βHSD2 with glycyrrhizic acid, the main sweet-tasting component of licorice, and by silencing the gene for 11βHSD2.
Both treatments inhibited the production of prostaglandin E2 (an inflammatory molecule produced by the COX-2 enzyme) and prevented the development of polyps (adenomas) and tumor growth and metastasis.
Because 11βHSD2 is highly expressed only in kidney and colon, blocking the enzyme produces effects specific to those tissues unlike NSAIDs, selective COX-2 inhibitors, and steroid treatments that can prevent cancer progression but also cause serious side effects like gastrointestinal irritation, cardiovascular events, and immunosuppression, respectively.
Licorice, Harris noted, has been used as a nutraceutical for thousands of years for ailments ranging from coughs to constipation. But even licorice is not without side effects; long-term consumption can lead to low blood potassium and increases in blood pressure side effects linked to the inhibition of 11βHSD2.
"These are relatively minor compared to the cardiovascular side effects of COX-2 inhibitors," Harris said. "We didn't see (these side effects) in the mice we treatedbut it would be something to be aware of, and something that could easily be treated with a diuretic."
Harris and colleagues are continuing to investigate the mechanism of 11βHSD2 inhibition. Zhang, an assistant profess
|Contact: Melissa Marino|
Vanderbilt University Medical Center