Cinnamaldehyde (CIN) has been shown to exert chemopreventive activity against several types of human cancer cells. We
previously reported that CIN induced apoptosis of human hepatoma PLC/PRF/5 cells and this effect was associated with activation of the
pro-apoptotic Bcl-2 family of proteins and the MAPK cascade. To further clarify the underlying mechanism of CIN-induced apoptosis,
we examined in this study its relationship with the mitochondrial death pathway using the mitochondrial permeability transition (MPT)
inhibitor, cyclosporin A (CsA), and the general caspase inhibitor, z-VAD-fmk. Results indicated that CIN-induced apoptosis involved
enhanced ROS generation, disruption of mitochondrial potential, and the mitochondrial release of cytochrome c and Smac/DIABLO into
the cytosol, which in turn promoted caspase-3 to its active form and the subsequent cleavage of PARP. Treatment with CIN also downregulated
protein levels of the anti-apoptotic factors XIAP and Bcl-2 with concomitant accumulation of the pro-apoptotic Bax in a timedependent
manner. These mitochondria-related apoptotic effects induced by CIN were however blocked by CsA and z-VAD-fmk
pretreatments, which prevented cells from undergoing programmed cell death triggered by CIN. Furthermore, the increase of Bax and
decrease of Bcl-2 and XIAP protein expression due to CIN treatment were also reversely modulated by the two inhibitors. Taken
together, these results suggested that CIN is an apoptotic inducer that acts on the mitochondrial death pathway in PLC/PRF/5 cells and its
effect could be blocked by CsA and z-VAD-fmk.
Keywords: Apoptosis, cinnamaldehyde, cyclosporin A, hepatoma, mitochondria, ROS, z-VAD-fmk.
Rights & PermissionsPrintExport