Apoptosis induction of U937 human leukemia cells by diallyl trisulfide induces through generation of reactive oxygen species

Yung Choi,Hyun Park

doi:10.1186/1423-0127-19-50

Abstract

BackgroundDiallyl trisulfide (DATS) is one of the major constituents in garlic oil and has demonstrated various pharmacological activities, including antimicrobial, antihyperlipidemic, antithrombotic, and anticancer effects. However, the mechanisms of antiproliferative activity in leukemia cells are not fully understood. In this study, the apoptotic effects of DATS were investigated in human leukemia cells.ResultsResults of this study indicated that treatment with DATS resulted in significantly inhibited leukemia cell growth in a concentration- and time-dependent manner by induction of apoptosis. In U937 cells, DATS-induced apoptosis was correlated with down-regulation of Bcl-2, XIAP, and cIAP-1 protein levels, cleavage of Bid proteins, activation of caspases, and collapse of mitochondrial membrane potential. The data further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, which was attenuated by pretreatment with antioxidant N-acetyl-l-cysteine (NAC), a scavenger of ROS. In addition, administration of NAC resulted in significant inhibition of DATS-induced apoptosis by inhibiting activation of caspases.ConclusionsThe present study reveals that the cytotoxicity caused by DATS is mediated by generation of ROS and subsequent activation of the ROS-dependent caspase pathway in U937 leukemia cells.

Highlights

Diallyl trisulfide (DATS) is one of the major constituents in garlic oil and has demonstrated various pharmacological activities, including antimicrobial, antihyperlipidemic, antithrombotic, and anticancer effects
Treatment with 20 μM DATS for 24 h and 48 h in U937 cells resulted in 53 % and 62 % inhibition, respectively, which was associated with many morphological changes (Figure 2A)
Induction of apoptosis in human leukemia cells by DATS In order to determine whether the decrease in leukemia cell viability by DATS treatment was due to induction of apoptosis, three established criteria were subsequently used for assessment of apoptosis

Summary

Introduction

Diallyl trisulfide (DATS) is one of the major constituents in garlic oil and has demonstrated various pharmacological activities, including antimicrobial, antihyperlipidemic, antithrombotic, and anticancer effects. Many researchers have recently demonstrated that sulfur-containing compounds, such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), which are major components of garlic, may be associated with reduced risk of certain cancers [18,19]. These compounds are known to inhibit cell proliferation and increase apoptosis in various cancer cell lines [20,21,22]. Others studies have supported the notion that DATS induces dramatic ROS generation in cancer cells through a mitochondrial pathway [26,28,29]. The cellular and molecular mechanisms underlying the compound have yet not been completely elucidated

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Results

Discussion

Conclusion