Q. Y. Choo, P. C. Ho and H. S. Lin Pages 803 - 820 ( 18 )
Histone deacetylase (HDAC) inhibitors are a new family of anti-cancer agents currently undergoing clinical investigations for various oncology indications. Their anti-inflammatory activities had been well documented and they appear to be potential therapeutic strategies for various inflammatory diseases. In this review, the anti-inflammatory activities of HDAC inhibitors with emphasis on their potential applications in rheumatoid arthritis (RA) will be summarized. The possible anti-rheumatic mechanisms, including growth arrest in rheumatoid arthritis synovial fibroblasts (RASFs), suppression of pro-inflammatory cytokines or chemokines, anti-angiogenesis as well as protective effects on bone and cartilage destruction will also be discussed. Current literatures strongly imply HDAC inhibitors as innovative anti-rheumatic drug candidates. However, long-term safety is a major concern. Future investigations should focus on identification of molecular anti-rheumatic mechanisms, development of new classes of HDAC inhibitors with better safety and selectivity profiles, combination of HDAC inhibitors with disease modifying anti-rheumatic drugs (DMARDs) and establishment of topical or intraarticular formulations.
Epigenetic regulation,histone deacetylase inhibitor,rheumatoid arthritis,growth arrest,pro-inflammatory cytokine,angiogenesis,osteoclastogenesis,nuclear factor kappa-B
, , Department of Pharmacy,National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260.