title: Curcumin induces apoptosis through an ornithine decarboxylase-dependent pathway in human promyelocytic leukemia HL-60 cells.
abstract: Curcumin, a well-known dietary pigment derived from the food flavoring turmeric (Curcuma longa) exhibits anti-proliferative, anti-inflammatory, and anti-oxidative activities. Recently, studies have shown that a chemopreventive effect of curcumin could be due to the hyperproduction of reactive oxygen species (ROS) inducing apoptosis in tumor cells. In our previous studies, ornithine decarboxylase (ODC) overexpression prevented tumor necrosis factor alpha (TNF-alpha)- and methotrexate-induced apoptosis via reduction of ROS. Furthermore, ODC is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. In this study, we found that enzyme activity and protein expression of ODC were reduced during curcumin treatment. Overexpression of ODC in human promyelocytic leukemia HL-60 parental cells could reduce curcumin-induced apoptosis, which leads to loss of mitochondrial membrane potential (Deltapsi(m)), through reducing intracellular ROS. Moreover, ODC overexpression prevented cytochrome c release and the activation of caspase-9 and caspase-3 following curcumin treatment. These results demonstrate that curcumin-induced apoptosis occurs through a mechanism of down-regulating ODC and along a ROS-dependent mitochondria-mediated pathway.
authors.affiliation: Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan, ROC.
authors.forename: Ya-Fan
authors.initials: YF
authors.lastname: Liao
authors.forename: Hui-Chih
authors.initials: HC
authors.lastname: Hung
authors.forename: Tzyh-Chyuan
authors.initials: TC
authors.lastname: Hour
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Hsu
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Kao
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsay
authors.forename: Guang-Yaw
authors.initials: GY
authors.lastname: Liu
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D003474:Curcumin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D065108:Ornithine Decarboxylase Inhibitors; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D009955:Ornithine Decarboxylase; D003474:Curcumin