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 (DeltaPsim), 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.
Ka
Hyeon
H
College of Pharmacy, Kyung-Hee University, Hoegi-Dong, Dongdaemun-Ku, Seoul 130-701, South Korea.
Park
Hee-Juhn
HJ
Jung
Hyun-Ju
HJ
Choi
Jong-Won
JW
Cho
Kyu-Seok
KS
Ha
Joohun
J
Lee
Kyung-Tae
KT
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D000171:Acrolein; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; C012843:cinnamaldehyde