Cytochrome C and Caspase-3/7 are Involved in Mycophenolic Acid-induced Apoptosis in Genetically Engineered PC12 Neuronal Cells Expressing the p53 Gene

Document Type: Research article

Authors

1 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

2 Department of Veterinary, Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3508 TD Utrecht, The Netherlands.

Abstract

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. This study designed to investigate the mechanism of cytotoxicity of MPA on the genetically engineered PC12 Tet Off (PTO) neuronal cells with p53 gene. Alamar Blue (AB) reduction showed concentration-dependent cytotoxicity of MPA on PTO cells with IC50 value of 32.32 ± 4.61 mM. The reactive oxygen species (ROS) generation following exposing the cells to MPA showed a significant (p < 0.05) increase in the ROS production and in a concentration-dependent fashion. Involvement of Caspase 3/7 proteases and Cytochrome C release in the induction of DNA fragmentation are all hallmarks of MPA-induced apoptosis in PTO cells. Our data suggest that MPA exerts an apoptotic effect on PTO cells. Moreover, the apoptotic effect of MPA attribute to the elevation of ROS generation by which might trigger the cytochrome C release and the activation of Caspase 3/7 that ultimately results in DNA fragmentation.

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