1.
Cinnamaldehyde has been shown to be effective in inducing cell apoptosis in a number of human
cancer cells. The aim of the present study was to investigate the effect of
vitamin E on the apoptotic signalling mechanism induced by
cinnamaldehyde in human
hepatoma PLC/PRF/5 cells. 2. Using the XTT assay,
cinnamaldehyde exhibited a powerful antiproliferative effect on PLC/PRF/5 cells. Apoptosis was elicited when cells were treated with 1 micromol/L
cinnamaldehyde, as characterized by the appearance of
phosphatidylserine on the outer surface of the plasma membrane. 3. The apoptotic effect induced by
cinnamaldehyde could be further supported by the release of
cytochrome c, Smac/Diablo and Omi/HtrA2 from mitochondria to the cytosol and activation of
caspase 3.
Cinnamaldehyde also upregulated the expression of
pro-apoptotic protein (Bax) and down-regulated the levels of
anti-apoptotic proteins, such as Bcl-2 and the
inhibitor of apoptosis protein family (
X-linked inhibitor of apoptosis protein (XIAP), cellular
inhibitor of apoptosis protein (cIAP)-1 and cIAP-2). 4.
Cinnamaldehyde induces the generation of
reactive oxygen species (ROS) in cells. Following the pre-incubation of PLC/PRF/5 cells with
anti-oxidants, it was found that 100 micromol/L
vitamin E significantly diminished the effect of
cinnamaldehyde-induced apoptosis, whereas a lesser effect was seen with on 100 micromol/L
N-acetyl-L-cysteine.
Vitamin E effectively blocked the release of
cytochrome c, Smac/Diablo and Omi/HtrA2 from mitochondria to the cytosol in cells treated with
cinnamaldehyde.
Vitamin E also markedly suppressed
caspase 3 activation. The expression of apoptotic inhibitors (XIAP, cIAP-1, cIAP-2) and anti-apoptotic (Bcl-2) and pro-apoptotic (Bax)
proteins was affected by
vitamin E pretreatment. 5. Taken together, the results suggest that
cinnamaldehyde triggers apoptosis possibly through the mitochondrial pathway. Pretreatment with
vitamin E markedly prevented
cinnamaldehyde-mediated apoptosis, which was associated with the modulation of XIAP, cIAP-1, cIAP-2, Bcl-2 and
Bax protein activity.