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.