mycophenolic-acid and Cell-Transformation--Neoplastic

Topics: Animals; Bacteria; Cell Differentiation; Cell Division; Cell Line; Cell Transformation, Neoplastic; Conserved Sequence; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; IMP Dehydrogenase; Isoenzymes; Mycophenolic Acid; Ribavirin; Sequence Homology, Amino Acid; Tumor Cells, Cultured

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.

Topics: Androgen Antagonists; Antibiotics, Antineoplastic; Biomarkers; Cell Cycle; Cell Differentiation; Cell Proliferation; Cell Transformation, Neoplastic; Drug Resistance, Neoplasm; Humans; Male; Mycophenolic Acid; Phenotype; Prostatic Neoplasms; Tumor Cells, Cultured

Mycophenolate mofetil (MM), an immunosuppressant used after organ transplantation, is also used for treatment of autoimmune myasthenia gravis (MG). A patient with generalized MG was effectively managed with MM but developed CNS lymphoma after 3 years of treatment. Primary CNS lymphoma regressed on withdrawal of MM. Despite minimal short-term side effects and apparent efficacy, chronic treatment of MG with MM may be associated with increased risk of lymphoproliferative disorders.

Topics: Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Brain Neoplasms; Cell Transformation, Neoplastic; Drug Therapy, Combination; Female; Frontal Lobe; Humans; Immunity, Cellular; Immunosuppressive Agents; Lymphoma, B-Cell; Magnetic Resonance Imaging; Myasthenia Gravis; Mycophenolic Acid; Parietal Lobe; Prednisone; Pyridostigmine Bromide; Rituximab; T-Lymphocytes; Treatment Outcome

Topics: Animals; Cell Communication; Cell Fusion; Cell Line; Cell Transformation, Neoplastic; Drug Resistance; Genetic Vectors; Mice; Mice, Nude; Mycophenolic Acid; Neoplasms; Plasmids