11β-Hydroxysteroid Dehydrogenase Type II is a Potential Target for Prevention of Colorectal Tumorigenesis
Journal Title: Journal of Oncobiomarkers - Year 2013, Vol 1, Issue 1
Abstract
Colorectal cancer (CRC) is a leading cause of cancer death, yet primary prevention remains the best approach to reducing overall morbidity and mortality. There is a clear molecular link between cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production and CRC progression. Although selective COX-2 inhibitors as well as non-steroidal anti-inflammatory drugs (NSAIDs) reduce the number and sizes of colonic adenomas, increased cardiovascular risks of selective COX-2 inhibitors and increased gastrointestinal side-effects of NSAIDs limit their use in chemoprevention of CRC. Glucocorticoids induce apoptosis and are endogenous, potent COX-2 inhibitors. Glucocorticoids have been used for the treatment of hematologic malignancies, but not for solid tumors due to adverse side-effects such as immunosuppression and osteoporosis. In tissues, glucocorticoid actions are down-regulated by type 2 11β-hydroxysteroid dehydrogenase (11βHSD2), and inhibition of 11βHSD2 activity will elevate intracellular active glucocorticoid to levels that effectively suppress COX-2 expression. Both COX-2 and 11βHSD2 increase in Apc+/min mouse intestinal adenomas and human colonic adenomas and either pharmacologic or genetic 11βHSD2 inhibition leads to decreases in COX-2-mediated PGE2 production in tumors and prevents adenoma formation, tumor growth, and metastasis. 11βHSD2 inhibition may represent a novel approach for CRC chemoprevention by increasing tumor cell intracellular glucocorticoid activity, which in turn inhibits tumor growth by suppressing the COX-2-derived PGE2 pathway, as well as other pathways, without potential side-effects relating to chronic application of COX-2 inhibitors, NSAIDs and glucocorticoids.
Authors and Affiliations
Ming Zhang
Keywords
Related Articles
- EP ID EP206201
- DOI 10.13188/2325-2340.1000002
- Views 82
- Downloads 0
IRF4 as an Oncogenic Biomarker for Hematological Malignancies
The lymphocyte-specific transcription factor Interferon (IFN) Regulatory Factor 4 (IRF4) is crucial for lymphocyte development. Importantly, IRF4 has potent oncogenic and transforming properties, and its intimate interac...
Recent Advances in Managementof Prostate Cancer
Prostate cancer is the second most common cancer in males worldwide and the incidence is increasing due to ageing population, screening facilities and rising awareness. This is a disease of the elderly and is biologicall...
Proteasome Subunit LMP2/β1i as a Biomarker for Human Uterine Mesenchymal Tumors
The proteasomal degradation pathway is essential for many cellular processes, including the cell cycle, regulation of gene expression, and responses to oxidative stress. The proteasome most exclusively used in mammals is...
Diets and Risk of Cancer
A new study is providing further evidence about the potentially life-threatening danger of drinking soda on a daily basis. Large, long-running epidemiological studies have also concluded that there is indeed a link betwe...
Involvement of Sphingosine Kinases/Sphingosine-1-Phosphate (S1P)/S1P Receptors in Breast Cancer Subtypes
There is emerging evidence suggesting sphingolipids as critical regulators of cancer development and progression. Sphingolipids are potent bioactive lipids involved in fundamental biological processes including cell prol...