Mycophenolic Acid Induced Apoptosis in Human Jurkat Cells viathe Generation of Reactive Oxygen Species

ABSTRACT

PURPOSE: Mycophenolic acid (MPA) is the active agent of mycophenolate mofetil (MMF), which is an immunosuppressive drug. MPA is a selective inhibitor of inosine monophosphate dehydrogenase. The aim of this study was for demonstrate that mycophenolic acid induces apoptosis in human Jurkat cells via the generation of reactive oxygen species (ROS). METHODS: The cells were cultured in the presence or absence of MPA. Flow cytometric analysis was performed after propidium iodide staining. Western blotting for caspase 3, Bcl-2 and Bax proteins was also performed. RESULTS: MPA decreased the viability of Jurkat cells in a dose- and time-dependent manner. The MPA induced apoptotic cell death displayed nuclear fragmentation and sub G0/G1 phase arrest in the Jurkat cells. The expression of caspase-3 proteases in the MPA treated-Jurkat cells increased in a time-dependent manner. Treatment with MPA resulted in increased ROS generation in the Jurkat cells. There was a decreased expression of Bcl-2 and an increased expression of Bax protein in the MPA treated Jurkat cells. CONCLUSION: This result suggests that MPA-induced cytotoxicity is associated with a direct increase of both ROS generation and the expression of Bax protein.