Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
Exp Mol Med. 2011 Apr 30;43(4):189-96. doi: 10.3858/emm.2011.43.4.023.
Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. Hydroxydibenzoylmethane (HDB), a derivative of dibenzoylmethane of licorice, is a promising chemopreventive agent. In this paper, we investigated whether HDB would inhibit the ODC pathway to enhance apoptosis in human promyelocytic leukemia HL-60 cells. We found ODC enzyme activity was reduced during HDB treatment. Overexpression of ODC in HL-60 parental cells could reduce HDB-induced apoptosis, which leads to loss of mitochondrial membrane potential (Δψ(m)), through lessening intracellular ROS. Furthermore, ODC overexpression protected cytochrome c release and the activation of caspase-3 following HDB treatment. The results demonstrated HDB-induced apoptosis was through a mechanism of down-regulation of ODC and occurred along a ROS-dependent mitochondria-mediated pathway.
鸟氨酸脱羧酶（ODC）是多胺生物合成中的限速酶，也是化学预防的靶点。羟二苯甲酮（HDB）是甘草二苯甲酮的衍生物，是一种很有前途的化学预防剂。在本文中，我们研究了 HDB 是否会抑制 ODC 途径以增强人早幼粒细胞白血病 HL-60 细胞的细胞凋亡。我们发现 HDB 处理期间 ODC 酶活性降低。在 HL-60 亲本细胞中过表达 ODC 可以通过减少细胞内 ROS 来减少 HDB 诱导的细胞凋亡，从而导致线粒体膜电位（Δψ（m））丧失。此外，ODC 过表达可保护细胞色素 c 释放和 caspase-3 在 HDB 处理后的激活。结果表明，HDB 诱导的细胞凋亡是通过下调 ODC 的机制发生的，并且沿着 ROS 依赖的线粒体介导的途径发生。
