Mycophenolic acid-induced replication arrest, differentiation markers and cell death of androgen-independent prostate cancer cells DU145

Inosine 5'-monophosphate dehydrogenase inhibitors including mycophenolic acid (MPA) are effective inducers of terminal differentiation in a variety of distinct human tumor cell types. Here, we report that MPA also induces such a differentiation in the androgen-independent prostate cancer derived cell line DU145. MPA evoked replication arrest and accumulation of the DU145 cells in the S-phase of the cell cycle. The inhibitor also induced the expression of CD55, clusterin, granulophysin, glucose-regulated protein 78, vasoactive intestinal polypeptide and prostate-specific transglutaminase, which are differentiation markers associated with the phenotype of normal prostate cells. We suggest that inosine 5'-monophosphate dehydrogenase inhibitors, which are already used for the treatment of other diseases, may be used as potential differentiation therapy drugs to control prostate cancer. (c) 2005 Elsevier Ireland Ltd. All rights reserved.