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KMID : 0613820070170121709
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Journal of Life Science
2007 Volume.17 No. 12 p.1709 ~ p.1716
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Water Extract of Allium sativum L. Induces Apoptosis in Human Leukemia U937 Cells through Reactive Oxygen Species Generation
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Choi Woo-Young
Chung Kyung-Tae
Yoon Tae-Kyung
Choi Byung-Tae
Lee Yong-Tae
Lee Won-Ho
Ryu Chung-Ho
Choi Yung-Hyun
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Abstract
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The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.
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KEYWORD
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Allium sativum, G2/M arrest, apoptosis, ROS, MMP
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