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

Ming-Fu Wang,Tzyh-Chyuan Hour,Hui-Chih Hung,Ya-Fan Liao,Chih-Li Lin,Guang-Yaw Liu,Ying-Cheng Hung,Ko-Huang Lue

doi:10.3858/emm.2011.43.4.023

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 (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.

Highlights

Hydroxydibenzoylmethane (HDB) is similar to curcumin and identical in structure to dibenzoylmethane (DB) that it possesses a hydroxyl group on one of the aromatic rings
Purified human Ornithine decarboxylase (ODC) recombinant protein was incubated with different concentrations of HDB for 1 h and the enzyme activity was determined by a luminescent assay
The results of the present study demonstrated for the first time that hydroxydibenzoylmethane (HDB) promoted human hematopoietic cell apoptosis

Summary

Introduction

Hydroxydibenzoylmethane (HDB) is similar to curcumin and identical in structure to dibenzoylmethane (DB) that it possesses a hydroxyl group on one of the aromatic rings. HDB is an inducer of phase 2 detoxification enzymes (Dinkova-Kostova and Talalay, 1999). The induction of phase 2 detoxification enzymes is a sufficient state for obtaining chemoprevention (Jana and Mandlekar, 2009). Chemopreventative strategies include preventing the initial development of cancer and the progression of an already established cancer. Apoptosis is triggered in a cell through two main signaling pathways, which are extrinsic and intrinsic pathways (Circu and Aw, 2010). The extrinsic pathway is activated from outside the cell by specific apoptotic ligands that interact with death receptors on the surface of cells. The intrinsic apoptotic pathway initiates in mitochondria. Recent report indicates that HDB is more potent than DB in repressing tumor proliferation and in the induction of caspase-3 and apoptotic cell death (Pan et al, 2003)

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