KMID : 0613820150250111235
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Journal of Life Science 2015 Volume.25 No. 11 p.1235 ~ p.1243
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Induction of Apoptosis by Hwangheuk-san in AGS Human Gastric Carcinoma Cells through the Generation of Reactive Oxygen Species and Activation of Caspases
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Hong Su-Hyun
Park Cheol Kim Kyung-Min Choi Yung-Hyun
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Abstract
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Hwangheuk-san (HHS) is a Korean multi-herb formula comprising four medicinal herbs. HHS, which was recorded in ¡°Dongeuibogam,¡± has been used to treat patients with inflammation syndromes and digestive tract cancer for hundreds of years. However, little is known about its anti-tumor efficacy. The present study investigated the pro-apoptotic effect and mode of action of HHS against AGS human gastric carcinoma cells. HHS inhibited the cell growth of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, chromatin condensation, and an accumulation of cells in the sub-G1 phase. HHS-induced apoptotic cell death was associated with the up-regulation of pro-apoptotic Bax protein expression, down-regulation of antiapoptotic Bcl-2 protein, and the release of cytochrome c from mitochondria to the cytosol. The treatment of AGS cells with HHS significantly elevated the generation of reactive oxygen species (ROS). Additionally, apoptosis-inducing concentrations of HHS induced the activation of both caspase-9 and -8, initiator caspases of the mitochondrial-mediated intrinsic and death receptor-mediated extrinsic pathways, respectively, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. However, ROS scavenger and pan-caspases inhibitor significantly blocked HHS-induced growth inhibition and apoptosis. Taken together, these findings suggest that HHS induces apoptosis through ROS- and caspase-dependent mechanisms and that HHS may be a potential chemotherapeutic agent for the control of human gastric cancer.
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KEYWORD
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AGS cells, apoptosis, caspase, Hwangheuk-san, ROS (reactive oxygen species)
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