Can licorice lick colon cancer?
Paul M. Stewart, Stephen M. Prescott
Paul M. Stewart, Stephen M. Prescott
Published March 23, 2009
Citation Information: J Clin Invest. 2009;119(4):760-763. https://doi.org/10.1172/JCI38936.
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Commentary

Can licorice lick colon cancer?

Abstract

COX-2 promotes colon cancer. While both nonselective NSAIDs and selective COX-2 inhibitors reduce disease burden, their adverse gastrointestinal and cardiovascular side effects limit their therapeutic use. In this issue of the JCI, Zhang et al. used gene silencing and a derivative of licorice root to show that inhibition of the enzyme 11β–hydroxysteroid dehydrogenase type II (11βHSD2) reduces tumor COX-2 activity, tumor growth, and metastasis by increasing the tonic glucocorticoid-mediated suppression of the COX-2 signaling pathway without the adverse effects associated with NSAIDs and selective COX-2 inhibitors (see the related article beginning on page 876). Their findings suggest that 11βHSD2 inhibition may be a potential therapeutic option in colon cancer, warranting further investigation.

Authors

Paul M. Stewart, Stephen M. Prescott

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Figure 1

Inhibition of 11βHSD2 blocks COX-2 and suppresses colon carcinogenesis.

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Inhibition of 11βHSD2 blocks COX-2 and suppresses colon carcinogenesis. ...
(A) In resting colon cells, COX-2 expression is suppressed by the binding of endogenous cortisol to the glucocorticoid (GC) receptor. (B) In the current study, Zhang et al. show that the expression of 11βHSD2 is increased both in human colon adenomas and in intestinal adenomas in Apc+/min mice (14). Active cortisol is converted by 11βHSD2 to inactive cortisone that is unable to activate the glucocorticoid receptor. This releases the repression of COX-2, which is then expressed at high levels and generates signals (primarily prostaglandins) that promote colon tumorigenesis. (C) The authors also show that these cellular events could be reversed — at least with regard to this signaling pathway — by inhibiting the enzymatic activity of 11βHSD2 via gene silencing or pharmacologically with the licorice root derivative GE. Under these conditions, cortisol is available to suppress COX-2 expression via the glucocorticoid receptor and therefore suppress tumorigenesis.