Hydroxydibenzoylmethane induces apoptosis through repressing ornithine decarboxylase in human promyelocytic leukemia HL-60 cells.
10.3858/emm.2011.43.4.023
- Author:
Ming Fu WANG
1
;
Ya Fan LIAO
;
Ying Cheng HUNG
;
Chih Li LIN
;
Tzyh Chyuan HOUR
;
Ko Huang LUE
;
Hui Chih HUNG
;
Guang Yaw LIU
Author Information
1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
hydroxydibenzoylmethane;
mitochondrial membrane potential;
ornithine decarboxylase;
reactive oxygen species
- MeSH:
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
- From:Experimental & Molecular Medicine
2011;43(4):189-196
- CountryRepublic of Korea
- Language:English
-
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.
