title: Ornithine decarboxylase prevents dibenzoylmethane-induced apoptosis through repressing reactive oxygen species generation.
abstract: Dibenzoylmethane (DBM) belongs to the flavonoid family and is a minor constituent of the root extract of licorice and the β-diketone analogue of curcumin. It exhibits antimutagenic, anticancer, and chemopreventive effects. Ornithine decarboxylase (ODC), the rate-limiting enzyme of the polyamine biosynthetic pathway, plays an important role in growth, proliferation, and transformation. Our previous studies showed ODC overexpression prevented etoposide-, paclitaxel-, and cisplatin-induced apoptosis. Here, we investigated one mechanism of DBM-induced apoptosis and the antiapoptotic effects of ODC during DBM treatment. We found that DBM induced apoptosis, promoted reactive oxygen species (ROS) generation, and disrupted the mitochondrial membrane potential (Δψ(m). N-acetylcysteine, a ROS scavenger, reduced DBM-induced apoptosis, which led to the loss of Δψ(m) due to reduced ROS. Overexpression of ODC in parental cells had the same effects as the ROS scavenger. The results demonstrated that DBM-induced apoptosis was a ROS-dependent pathway and ODC overexpression blocked DBM-induced apoptosis by inhibiting intracellular ROS production.
authors.affiliation: School of Medicine and Institute of Medicine, Chung Shan Medical University and Department of Orthopaedic Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Wu
authors.forename: Ya-Fan
authors.initials: YF
authors.lastname: Liao
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Hung
authors.forename: Ko-Hsiu
authors.initials: KH
authors.lastname: Lu
authors.forename: Hui-Chih
authors.initials: HC
authors.lastname: Hung
authors.forename: Guang-Yaw
authors.initials: GY
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D003474:Curcumin / Q000737:chemistry; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015870:Gene Expression; D006035:Glycyrrhiza / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010957:Plasmids; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D047188:Chalcones; D016166:Free Radical Scavengers; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C061481:dibenzoylmethane; D009955:Ornithine Decarboxylase; D003474:Curcumin; D000111:Acetylcysteine