La sabrosa regaliz puede ayudar a prevenir el cáncer de colon reduciendo adenomas de colon

[Mercè Ortiz]

Published in Volume 119, Issue 4 (April 1, 2009)
J. Clin. Invest. 119(4): 876-885 (2009). doi:10.1172/JCI37398.
Copyright © 2009, The American Society for Clinical Investigation
Research Article
Inhibition of 11β–hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans

Ming-Zhi Zhang1,2, Jie Xu1, Bing Yao1, Huiyong Yin1, Qiuyin Cai1, Martha J. Shrubsole1, Xiwu Chen1, Valentina Kon3, Wei Zheng1, Ambra Pozzi1 and Raymond C. Harris1

1Department of Medicine,
2Department of Cancer Biology, and
3Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Address correspondence to: Ming-Zhi Zhang, S-3223 MCN, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. Phone: [phone]; Fax: [phone]; E-mail: [e-mail]. Or to: Raymond Harris, C3121 MCN, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. Phone: [phone]; Fax: [phone]; E-mail: [e-mail].

First published March 23, 2009
Received for publication September 9, 2008, and accepted in revised form February 11, 2009.

Colorectal cancer (CRC) is a leading cause of cancer death, yet primary prevention remains the best approach to reducing overall morbidity and mortality. Studies have shown that COX-2–derived PGE2 promotes CRC progression, and both nonselective COX inhibitors (NSAIDs) and selective COX-2 inhibitors (such as glucocorticoids) reduce the number and size of colonic adenomas. However, increased gastrointestinal side effects of NSAIDs and increased cardiovascular risks of selective COX-2 inhibitors limit their use in chemoprevention of CRC. We found that expression of 11β–hydroxysteroid dehydrogenase type II (11βHSD2), which converts active glucocorticoids to inactive keto-forms, increased in human colonic and Apc+/min mouse intestinal adenomas and correlated with increased COX-2 expression and activity. Furthermore, pharmacologic inhibition or gene silencing of 11βHSD2 inhibited COX-2–mediated PGE2 production in tumors and prevented adenoma formation, tumor growth, and metastasis in mice. Inhibition of 11βHSD2 did not reduce systemic prostacyclin production or accelerate atherosclerosis in mice, thereby avoiding the major cardiovascular side effects seen with systemic COX-2 inhibitors. Therefore, 11βHSD2 inhibition represents what we believe to be a novel approach for CRC chemoprevention and therapy by increasing tumor glucocorticoid activity, which in turn selectively blocks local COX-2 activity.