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Apoptosis induction of U937 human leukemia cells by diallyl trisulfide induces through generation of reactive oxygen species
1 Department of Biochemistry, Dongeui University College of Oriental Medicine, San 45, Yangjung-dong Busanjin-gu, Busan, 614-052, Republic of Korea
2 Department of Biomaterial Control and Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, 995 Eomgwangno Busanjin-gu, Busan, 614-714, Republic of Korea
Journal of Biomedical Science 2012, 19:50 doi:10.1186/1423-0127-19-50Published: 11 May 2012
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. 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.
Results 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.
The 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.