Exp Mol Med.  2011 Apr;43(4):189-196. 10.3858/emm.2011.43.4.023.

Hydroxydibenzoylmethane induces apoptosis through repressing ornithine decarboxylase in human promyelocytic leukemia HL-60 cells

Affiliations
  • 1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
  • 2Department of Pediatrics, Tung's Taichung MetroHarbor Hospital, Wuchi, Taiwan, ROC.
  • 3Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Wufong, Taiwan, ROC.
  • 4Institute of Microbiology & Immunology, Chung Shan Medical University, Division of Allergy, Immunology, and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC. liugy@csmu.edu.tw
  • 5Institute of Biochemistry, College of Medicine, Kaohsiung Medical University Kaohsiung, Taiwan, ROC.
  • 6Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, ROC.

Abstract

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 (Deltapsim), 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.

Keyword

apoptosis; hydroxydibenzoylmethane; mitochondrial membrane potential; ornithine decarboxylase; reactive oxygen species

MeSH Terms

Apoptosis/*drug effects
Caspase 3/metabolism
Chalcones/metabolism/*pharmacology
Chemoprevention
Cytochromes c/biosynthesis/secretion
Down-Regulation
Gene Expression
HL-60 Cells
Humans
Immunoblotting
Leukemia, Myeloid/*enzymology/pathology
Membrane Potential, Mitochondrial/drug effects
Mitochondria/enzymology
Ornithine Decarboxylase/antagonists & inhibitors/genetics/*metabolism
Reactive Oxygen Species/analysis/metabolism
Reverse Transcriptase Polymerase Chain Reaction
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