Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells

Cinnamaldehyde is an active compound isolated from the stem bark of Cinnamomum cassia,a traditional oriental medicinal herb, which has been shown to inhibit tumor cell proliferation. In this study, we investigated the effects of cinnamaldehyde on the cytotoxicity, induction of apoptosis and the putative pathways of its actions in human promyelocytic leukemia cells. Using apoptosis analysis, measurement of reactive oxygen species (ROS), and assessment of mitochondrial membrane potentials (Deltapsi(m)), we show that cinnamaldehyde is a potent inducer of apoptosis and that it transduces the apoptotic signal via ROS generation. thereby inducing mitochondrial permeability transition (MPT) and cytochrome c release to the cytosol. ROS production, mitochondrial alteration, and subsequent apoptotic cell death in cinnamaldehyde-treated cells were blocked by the antioxidant N-acetylcystein. Taken together, our data indicate that cinnamaldehyde induces the ROS-mediated mitochondrial permeability transition and resultant cytochrome c release. This is the first report on the mechanism of the anticancer effect of cinnamaldehyde. (C) 2003 Elsevier Science Ltd. All rights reserved.