J Korean Surg Soc.  2008 Sep;75(3):149-155.

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

• Lee DK
• Lee HK
• Choi SJ
• Chung SY

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.

Keyword

Mycophenolic acid; Reactive oxygen species; Immunosuppressive agent

MeSH Terms

Apoptosis
bcl-2-Associated X Protein
Blotting, Western
Caspase 3
Cell Death
Humans
Inosine Monophosphate
Jurkat Cells
Mycophenolic Acid
Oxidoreductases
Peptide Hydrolases
Propidium
Reactive Oxygen Species
Caspase 3
Inosine Monophosphate
Mycophenolic Acid
Oxidoreductases
Peptide Hydrolases
Propidium
Reactive Oxygen Species
bcl-2-Associated X Protein