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http://dx.doi.org/10.5352/JLS.2015.25.11.1235

Induction of Apoptosis by Hwangheuk-san in AGS Human Gastric Carcinoma Cells through the Generation of Reactive Oxygen Species and Activation of Caspases  

Hong, Su Hyun (Department of Biochemistry, Dongeui University College of Korean Medicine)
Park, Cheol (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University)
Kim, Kyoung Min (Department of Caridovascular & Neurologic Disease, College of Korean Medicine, Dongeui University)
Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Korean Medicine)
Publication Information
Journal of Life Science / v.25, no.11, 2015 , pp. 1235-1243 More about this Journal
Abstract
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.
Keywords
AGS cells; apoptosis; caspase; Hwangheuk-san; ROS (reactive oxygen species);
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