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标题：Effects of the Ethylacetate Extract of Orostachys japonicus on Induction of Apoptosis through the p53-Mediated Signaling Pathway in Human Gastric Cancer Cells
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作者：Deok-Seon Ryu ; Hyeong-Seon Lee ; Gyeong-Seon Lee 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2012
卷号：35
期号：5
页码：660-665
DOI：10.1248/bpb.35.660
出版社：The Pharmaceutical Society of Japan
摘要：Cancer rates are increasing dramatically, and there is currently a strong emphasis on identifying biologically active substances with anti-cancer activity from traditional herbs, as these are thought to have less adverse side-effects than conventional chemotherapy. Here, we examined the effects of extracts of Orostachys japonicus A. B ERGER ( O. japonicus ) on cancer cell proliferation and apoptosis, and investigated the underlying signaling pathways. Dried powdered O. japonicus was extracted with 95% ethyl alcohol and fractionated with a series of organic solvents, including n -hexane (hexane), dichloromethane (DCM), ethylacetate (EtOAc), n -butanol (BuOH), and water (H₂O). These extracts were tested for anti-cancer activity on a range of cancer cells; of all these, the EtOAc soluble fraction showed the highest anti-cancer activity, which was most marked in AGS human gastric cancer cells. The EtOAc fraction inhibited the proliferation of AGS cells in a dose-dependent and time-dependent manner, by inducing apoptosis and cell cycle arrest, as evidenced by 4,6-diamidino-2-phenylindole (DAPI) staining, annexin V-fluorescein isothiocyanate staining, propidium iodide-labeling, and DNA fragmentation assays. Western blot analysis revealed that p53 and cleaved caspase-3 proteins were up-regulated, and B cell lymphoma-2 (bcl-2) protein and pro-caspase-3 were down-regulated, but bcl-2 associated x protein (bax) protein was not regulated, in response to treatment of AGS cells with the EtOAc fraction. However, the changes of pro-caspase-3 and cleaved caspase-3 could be abolished by the pan-caspase inhibitor Z-VAD-FMK. These results suggest the EtOAc fraction from O. japonicus has substantial anti-cancer activity in human gastric cancer cells.
关键词：Orostachys japonicus;human gastric cancer cell line;ethylacetate fraction;anti-cancer activity