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.
Floryk
Daniel
D
Gene Expression Group-Energy Systems Division, Argonne National Laboratory, 9700 S Cass Ave, Bldg 202, Argonne, IL 60439, USA.
Huberman
Eliezer
E
D000726:Androgen Antagonists / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009173:Mycophenolic Acid / Q000494:pharmacology*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D009173:Mycophenolic Acid