Molecular Basis of Histone Deacetylase Inhibitors as New Drugs for the Treatment of Inflammatory Diseases and Cancer
Histone deacetylase inhibitors are potent inducers of growth arrest and apoptotic cell death and are currently in clinical studies for solid tumors. In addition, recent studies from our own group provide evidence for an anti-inflammatory potency of HDACi in vitro and in vivo by using various models of experimental colitis. Since inflammatory bowel disease in humans is associated with an increased risk of developing colorectal cancer, a therapeutic approach combining anti-inflammatory as well as antiprolif-erative properties is highly intriguing. Consequently, methods to further characterize the mechanisms involved include the direct analysis of the acetylation/deacetylation as well as the regulatory effect of histone deacetylase inhibitors on defined cell populations.
Key wordsHistones Acetylation Inflammation Epigenetic Thelper cells Apoptosis
- 3.Leoni, F., Zaliani, A., Bertolini, G., Porro, G., Pagani, P., Pozzi, P. , Dona, G., Fossati, G., Sozzani, S., Azam, T., Bufler, P. , Fantuzzi, G., Goncharov, I., Kim, S. H., Pomerantz, B. J., Reznikov, L. L., Siegmund, B., Dinarello, C. A., and Mascagni, P. (2002) The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines Proc Natl Acad Sci USA 99, 2995–3000.CrossRefPubMedGoogle Scholar